Trial Outcomes & Findings for Ketorolac Versus Ibuprofen to Treat Painful Episodes of Sickle Cell Disease (NCT NCT00115336)
NCT ID: NCT00115336
Last Updated: 2020-10-08
Results Overview
The primary endpoint is the time to a 50% reduction in reported pain intensity. This endpoint is relative to the baseline pain intensity rating on the Oucher scale (minimum 0, maximum 10; higher scores indicate greater pain). The endpoint will be reached when the reported pain intensity is at least one-half of the baseline value on two consecutive measurements at least 4 hours apart. The time ascribed to the endpoint will be the time of the second of these two consecutive pain scales. Participants who do not have a 50% reduction in reported pain intensity, as defined above, before discharge from the hospital will be censored at the time of last rating on the Oucher pain scale before discharge from the hospital
TERMINATED
PHASE4
10 participants
Measured every 4 hours during hospitalization, over a mean hospitalization duration of 81.5 hours.
2020-10-08
Participant Flow
Planned enrollment for the trial was 120 subjects. Accrual was extremely slow; only 10 participants were randomized before the trial was closed in 2008 due to lack of accrual. Less than 10% of planned enrollment was achieved.
Participant milestones
| Measure |
IV Ketorolac / Oral Placebo
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
4
|
|
Overall Study
COMPLETED
|
6
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
IV Ketorolac / Oral Placebo
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Overall Study
Hospital discharge before study drug
|
0
|
1
|
Baseline Characteristics
Ketorolac Versus Ibuprofen to Treat Painful Episodes of Sickle Cell Disease
Baseline characteristics by cohort
| Measure |
IV Ketorolac / Oral Placebo
n=6 Participants
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
n=4 Participants
Intravenous placebo abd oral ibuprofen
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
15.4 years
n=99 Participants
|
17.7 years
n=107 Participants
|
16.7 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=99 Participants
|
4 participants
n=107 Participants
|
10 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Measured every 4 hours during hospitalization, over a mean hospitalization duration of 81.5 hours.Population: One participant was randomized but was discharged (unexpectedly early) from the hospital before study drug was administered. Thus, no primary or secondary outcome data are available for this one participant.
The primary endpoint is the time to a 50% reduction in reported pain intensity. This endpoint is relative to the baseline pain intensity rating on the Oucher scale (minimum 0, maximum 10; higher scores indicate greater pain). The endpoint will be reached when the reported pain intensity is at least one-half of the baseline value on two consecutive measurements at least 4 hours apart. The time ascribed to the endpoint will be the time of the second of these two consecutive pain scales. Participants who do not have a 50% reduction in reported pain intensity, as defined above, before discharge from the hospital will be censored at the time of last rating on the Oucher pain scale before discharge from the hospital
Outcome measures
| Measure |
IV Ketorolac / Oral Placebo
n=6 Participants
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
n=3 Participants
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Time to a 50% Reduction in Reported Pain Intensity
|
58.4 hours
Interval 29.3 to 87.4
|
68.0 hours
Interval 20.3 to 115.8
|
SECONDARY outcome
Timeframe: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.Population: One participant was randomized but was discharged (unexpectedly early) from the hospital before study drug was administered. Thus, no primary or secondary outcome data are available for this one participant.
Time between admission to the hospital and discharge from the hospital
Outcome measures
| Measure |
IV Ketorolac / Oral Placebo
n=6 Participants
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
n=3 Participants
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Duration of Hospitalization
|
80.7 hours
Interval 19.3 to 142.1
|
83.0 hours
Interval 27.2 to 138.7
|
SECONDARY outcome
Timeframe: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.Population: One participant was randomized but was discharged (unexpectedly early) from the hospital before study drug was administered. Thus, no primary or secondary outcome data are available for this one participant.
Sum of all parenteral opioids used during the study period in milligrams (mg) of morphine or morphine equivalents.
Outcome measures
| Measure |
IV Ketorolac / Oral Placebo
n=6 Participants
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
n=3 Participants
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Total Parenteral Opioid Usage
|
225.2 milligrams (mg) of morphine equivalents
Interval 17.0 to 433.3
|
264.6 milligrams (mg) of morphine equivalents
Interval 0.0 to 530.8
|
SECONDARY outcome
Timeframe: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.Population: Extremely slow accrual led to the trial closing in 2008. Because only 10% of planned enrollment was achieved, no analysis of the primary or secondary outcome data was performed because of lack of power and generalizability.
Participants who had measured values of blood urea nitrogen (BUN), serum creatinine, or both that were above the upper limit of normal for age.
Outcome measures
| Measure |
IV Ketorolac / Oral Placebo
n=6 Participants
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
n=3 Participants
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Occurrence of Azotemia
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: The entire study period (daily assessments during hospitalization [mean of 81.5 hours] and once at the 30-day follow-up visit, over a mean of 33.4 days)Population: One participant was randomized but was discharged (unexpectedly early) from the hospital before study drug was administered. Thus, no primary or secondary outcome data are available for this one participant.
Number of participants who had clinically overt fluid retention as determined by history, physical examination, vital signs, and weight (e.g., peripheral edema, increase in weight)
Outcome measures
| Measure |
IV Ketorolac / Oral Placebo
n=6 Participants
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
n=3 Participants
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Fluid Retention
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.Population: One participant was randomized but was discharged (unexpectedly early) from the hospital before study drug was administered. Thus, no primary or secondary outcome data are available for this one participant.
Number of participants who had microscopic hematuria as determined by urinalysis
Outcome measures
| Measure |
IV Ketorolac / Oral Placebo
n=6 Participants
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
n=3 Participants
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Hematuria
|
4 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: The entire study period (daily assessments during hospitalization [mean of 81.5 hours] and once at the 30-day follow-up visit, over a mean of 33.4 days)Population: One participant was randomized but was discharged (unexpectedly early) from the hospital before study drug was administered. Thus, no primary or secondary outcome data are available for this one participant.
Number of participants who reported discomfort in the stomach related to eating or drinking
Outcome measures
| Measure |
IV Ketorolac / Oral Placebo
n=6 Participants
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
n=3 Participants
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Dyspepsia
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: The entire study period (daily assessments during hospitalization [mean of 81.5 hours] and once at the 30-day follow-up visit, over a mean of 33.4 days)Population: One participant was randomized but was discharged (unexpectedly early) from the hospital before study drug was administered. Thus, no primary or secondary outcome data are available for this one participant.
Number of participants who had gastrointestinal ulceration.
Outcome measures
| Measure |
IV Ketorolac / Oral Placebo
n=6 Participants
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
n=3 Participants
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Gastrointestinal Ulceration
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: The entire study period (daily assessments during hospitalization [mean of 81.5 hours] and once at the 30-day follow-up visit, over a mean of 33.4 days)Population: One participant was randomized but was discharged (unexpectedly early) from the hospital before study drug was administered. Thus, no primary or secondary outcome data are available for this one participant.
Number of participants who had clinically overt bleeding from any site. This excludes microscopic hematuria only.
Outcome measures
| Measure |
IV Ketorolac / Oral Placebo
n=6 Participants
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
n=3 Participants
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Bleeding
|
0 Participants
|
0 Participants
|
Adverse Events
IV Ketorolac / Oral Placebo
IV Placebo / Oral Ibuprofen
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
IV Ketorolac / Oral Placebo
n=6 participants at risk
Intravenous ketorolac and oral placebo
|
IV Placebo / Oral Ibuprofen
n=4 participants at risk
Intravenous placebo and oral ibuprofen
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
25.0%
1/4 • Number of events 1 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
3/6 • Number of events 3 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
25.0%
1/4 • Number of events 1 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
50.0%
3/6 • Number of events 3 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
50.0%
2/4 • Number of events 2 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
|
Renal and urinary disorders
Urinary Retention
|
16.7%
1/6 • Number of events 1 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
0.00%
0/4 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
|
Immune system disorders
Fever
|
16.7%
1/6 • Number of events 1 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
25.0%
1/4 • Number of events 1 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
|
Respiratory, thoracic and mediastinal disorders
Acute chest syndrome
|
16.7%
1/6 • Number of events 1 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
0.00%
0/4 • 30 days
All adverse events were systematically assessed at all study visits according to the study protocol by trained study personnel. Adverse events were recorded for up to 30 days from discharge from the hospital.
|
Additional Information
Dr. Charles Quinn
Cincinnati Children's Hospital Medical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place