Trial Outcomes & Findings for Randomized Controlled Trial to Evaluate the Safety and Efficacy of Acetaminophen in Preterm Infants Used in Combination With Ibuprofen for Closure of the Ductus Arteriosus (NCT NCT03701074)

Results Overview

Ductal closure/constriction rate as defined based on the echocardiographic findings. Ductal closure/constriction will be defined as the complete closure of ductus or ductal diameter \<1 mm

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

1 participants

Primary outcome timeframe

24-48 hours after the completion of study intervention

Results posted on

2026-04-30

Participant Flow

Overall screening for the study enrollment started 12/15/2018. Screening was continued until 10/30/2020. The study was conducted at the Neonatal Intensive Care Unit

Participant milestones

Participant milestones
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Overall Study STARTED	1	0
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Overall Study Physician Decision	1	0

Baseline Characteristics

Randomized Controlled Trial to Evaluate the Safety and Efficacy of Acetaminophen in Preterm Infants Used in Combination With Ibuprofen for Closure of the Ductus Arteriosus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo	Total n=1 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=14 Participants	0 Participants n=34 Participants	1 Participants n=69 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants
Age, Categorical >=65 years	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants
Sex: Female, Male Female	1 Participants n=14 Participants	0 Participants n=34 Participants	1 Participants n=69 Participants
Sex: Female, Male Male	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=14 Participants	—	0 Participants n=69 Participants
Race (NIH/OMB) Asian	0 Participants n=14 Participants	—	0 Participants n=69 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=14 Participants	—	0 Participants n=69 Participants
Race (NIH/OMB) Black or African American	0 Participants n=14 Participants	—	0 Participants n=69 Participants
Race (NIH/OMB) White	1 Participants n=14 Participants	—	1 Participants n=69 Participants
Race (NIH/OMB) More than one race	0 Participants n=14 Participants	—	0 Participants n=69 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=14 Participants	—	0 Participants n=69 Participants
Region of Enrollment United States	1 participants n=14 Participants	—	1 participants n=69 Participants
PDA size	1.5 mm n=14 Participants	—	1.5 mm n=69 Participants

PRIMARY outcome

Timeframe: 24-48 hours after the completion of study intervention

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm). The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible.

Ductal closure/constriction rate as defined based on the echocardiographic findings. Ductal closure/constriction will be defined as the complete closure of ductus or ductal diameter \<1 mm

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants With Ductus Arteriosus Closure/Constriction	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 24-48 hours after the completion of study intervention

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a continuous variable with an intended between-group and within the group comparisons. The planned analysis is not possible due to the enrollment of only one infant. Hence, no comparative or inferential statistical analysis was performed

Echocardiographic parameters including ductal size (PDA size in mm), Left atrium to aortic root ratio, ductal velocity, descending aortic diastolic flow, before and after the intervention. Between the group and within the group comparison

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24-48 hours after the completion of study intervention

Population: None were enrolled for the control arm. The study was terminated (very slow enrollment. Only one patient enrolled. Termination by PI). Only one infant in the intervention arm and the the specified outcome measure is a continuous variable with intended between group and within group comparison, the planned analysis is not possible due only one infant enrollment. Hence, no comparative or inferential statistical analysis was performed.

Ventilator parameters including Fio2, Mean airway pressure, Peak Inspiratory pressure, PEEP, and ventilatory rate oxygenation indices including Oxygenation index and Respiratory Severity score before and after intervention

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24-48 hours after the completion of study intervention

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible.

liver enzymes compared before and after the study intervention; if any significant elevation of liver enzymes from baseline, the participant classified as having liver injury

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants With Liver Injury	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 24-48 hours after the completion of study intervention

Population: Overall, only one infant was enrolled into the study. One in the intervention arm and none in the control arm. The study was terminated (very slow enrollment. Only one patient enrolled. Termination by PI) The specific outcome measure is a categorical variable. As only one infant was enrolled, the data is provided as count. Any comparison between group and inferential statistics is not possible as only one infant was enrolled

Blood urea nitrogen (BUN) and serum creatinine before and after the study intervention are compared. Participants exhibiting significant elevation BUN and S creatine, are classified as having renal injury

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants With Renal Injury	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 24-48 hours after the completion of study intervention

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible.

Hematocrit and platelet counts compared before and after the study intervention; if any significant alteration from baseline, the participant classified as having hematological adverse event,

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants With Hematological Adverse Events	0 Participants	0 Participants

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a continuous variable with an intended between-group comparison. The planned analysis is not possible due to the enrollment of only one infant. Hence, no comparative or inferential statistical analysis was performed

The total number of days on mechanical ventilation are counted as total duration of conventional mechanical ventilation plus high frequency ventilatory days

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a continuous variable with an intended between-group comparison. The planned analysis is not possible due to the enrollment of only one infant. Hence, no comparative or inferential statistical analysis was performed

Cumulative days on any supplemental O2 (including Mechanical ventilation., noninvasive ventilation, nasal cannula support) calculated from randomization until 4 weeks of postmenstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm). The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a continuous variable with an intended between-group comparison. The planned analysis is not possible due to the enrollment of only one infant. Hence, no comparative or inferential statistical analysis was performed.

Total cumulative days on noninvasive ventilation, including NIPPV and nasal CPAP,

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible

Proportion of participants in each group requiring open label treatment with pharmacological agents for ductal closure, e.g. IV Ibuprofen or IV Acetaminophen or IV indomethacin therapies, as decided by the treating physician

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants With Persistence of Ductus-needing Pharmacological Treatment	1 Participants	0 Participants

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible

Proportion of participants in each group requiring surgical ligation of persistent PDA for definitive surgical closure

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants Requiring Surgical Ligation of PDA	0 Participants	0 Participants

SECONDARY outcome

Timeframe: at 36 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm). The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible

Proportion of participants diagnosed to have BPD based supplemental O2 requirement at 36 weeks' postmenstrual age

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants Developing Bronchopulmonary Dysplasia	0 Participants	0 Participants

SECONDARY outcome

Timeframe: at discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and the infant developed in-hospital mortality prior to the initial discharge. Hence, this outcome is not applicable. Additionally, as no one enrolled in the control arm, no inferential statistics are possible.

Proportion of participants in each group requiring home-based supplemental O2 therapy following the initial discharge from hospital.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible.

Proportion of participants in each group developing in-hospital death prior to 40 weeks of postmenstrual age.

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants Developing Death Before Discharge	1 Participants	0 Participants

SECONDARY outcome

Timeframe: from birth until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a continuous variable with an intended between-group comparison. The planned analysis is not possible due to the enrollment of only one infant. Hence, no comparative or inferential statistical analysis was performed.

Duration days during the postnatal period required to achieve an enteral feeding volume of 120 ml/kg/day.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from birth until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a continuous variable with an intended between-group comparison. The planned analysis is not possible due to the enrollment of only one infant. Hence, no comparative or inferential statistical analysis was performed.

Cumulative days of receiving total parental nutrition from birth until the participant is discharged or reached postmenstrual age of 40 weeks

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from birth until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible.

Proportion of participants in each group diagnosed to have retinopathy of prematurity

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants With Retinopathy of Prematurity	1 Participants	0 Participants

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible.

Proportion of participants developing or having the diagnosis of spontaneous intestinal perforation from randomization until discharge or 40 weeks' Postmenstrual age

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants Developing Spontaneous Intestinal Perforation	0 Participants	0 Participants

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible.

Proportion of participants in each group with the diagnosis of medical or surgical Necrotizing Enterocolitis

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants Developing Necrotizing Enterocolitis	1 Participants	0 Participants

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible.

Proportion of participants in each group developing gastrointestinal hemorrhage following randomization until discharge or postmenstrual age of 40 weeks

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants Developing Gastrointestinal Hemorrhage	0 Participants	0 Participants

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible.

Proportion of participants diagnosed to have either probable sepsis with minimum of 7 days of antibiotic therapy or culture proven sepsis

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants Developing Late Onset Sepsis	1 Participants	0 Participants

SECONDARY outcome

Timeframe: from birth until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a continuous variable with an intended between-group comparison. The planned analysis is not possible due to the enrollment of only one infant. Hence, no comparative or inferential statistical analysis was performed.

Total duration (in days ) of hospital stay

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Population: Overall, only one participant was enrolled into the study (one in the intervention arm and none in the control arm. The study was terminated (very slow enrolment, termination by PI). The specified outcome measure is a categorical variable, and as only one infant was enrolled, the outcome has been reported as a count. As no one enrolled in the control arm, no inferential statistics are possible.

Proportion of participants in each group with the evidence of periventricular leukomalacia on neurosonography

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Proportion of Participants With Periventricular Leukomalacia	0 Participants	0 Participants

Adverse Events

Ibuprofen and Acetaminophen Arm (Intervention Arm)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 1 deaths

Ibuprofen and Placebo Arm (Control Arm)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 participants at risk ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Renal and urinary disorders Biochemical evidence of acute kidney injury with preserved renal function, probably nor related to i	100.0% 1/1 • 4 months None were enrolled into control arm, Therefore, number infants at risk for adverse events under the control arm are zero	— 0/0 • 4 months None were enrolled into control arm, Therefore, number infants at risk for adverse events under the control arm are zero

Additional Information

Ramachandra Bhat

University of South Alabama

Phone: 2514151055

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place