Trial Outcomes & Findings for Flumazenil for Hypoactive Delirium Secondary to Benzodiazepine Exposure (NCT NCT02899156)
NCT ID: NCT02899156
Last Updated: 2020-07-23
Results Overview
Defined by the number of days in the 14-day period after randomization that the patient was alive and not delirious (i.e. CAM-ICU negative). Zero delirium-free days will be observed for patients that die within the 14-day period.
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
22 participants
Primary outcome timeframe
up to 14 days after randomization
Results posted on
2020-07-23
Participant Flow
Participant milestones
| Measure |
Flumazenil Group
The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Flumazenil
|
Placebo Group
The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Placebo: 0.9% normal saline
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
11
|
|
Overall Study
COMPLETED
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Flumazenil Group
The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Flumazenil
|
Placebo Group
The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Placebo: 0.9% normal saline
|
|---|---|---|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Flumazenil Infusion
n=11 Participants
The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Flumazenil
|
Placebo Infusion
n=11 Participants
The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Placebo: 0.9% normal saline
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58 years
STANDARD_DEVIATION 7 • n=11 Participants
|
59.4 years
STANDARD_DEVIATION 7.6 • n=11 Participants
|
58.9 years
STANDARD_DEVIATION 7.2 • n=22 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=11 Participants
|
3 Participants
n=11 Participants
|
7 Participants
n=22 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=11 Participants
|
8 Participants
n=11 Participants
|
15 Participants
n=22 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
11 Participants
n=11 Participants
|
11 Participants
n=11 Participants
|
22 Participants
n=22 Participants
|
|
Days in Hospital Prior to Enrollment
|
8.5 days
STANDARD_DEVIATION 2.8 • n=11 Participants
|
10.6 days
STANDARD_DEVIATION 7.5 • n=11 Participants
|
9.5 days
STANDARD_DEVIATION 5.8 • n=22 Participants
|
|
Time Since Last Benzodiazepine
|
43 hours
STANDARD_DEVIATION 23 • n=11 Participants
|
55 hours
STANDARD_DEVIATION 37.1 • n=11 Participants
|
49 hours
STANDARD_DEVIATION 31.5 • n=22 Participants
|
|
Lorazepam Equivalents
|
117 milligrams
n=11 Participants
|
110.3 milligrams
n=11 Participants
|
113.6 milligrams
n=22 Participants
|
PRIMARY outcome
Timeframe: up to 14 days after randomizationPopulation: One patient randomized to the flumazenil and one randomized to the placebo never received the study infusion. The patient in the flumazenil group died from a massive hemorrhage within 1 hour of infusion initiation, and it was deemed nonattributable to study infusion. Twenty patients were included in the final analysis.
Defined by the number of days in the 14-day period after randomization that the patient was alive and not delirious (i.e. CAM-ICU negative). Zero delirium-free days will be observed for patients that die within the 14-day period.
Outcome measures
| Measure |
Flumazenil Group
n=10 Participants
The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Flumazenil
|
Placebo Group
n=10 Participants
The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Placebo: 0.9% normal saline
|
|---|---|---|
|
Number of Delirium-free Days
|
12.7 days
Interval 7.2 to 13.2
|
9.2 days
Interval 0.0 to 10.2
|
SECONDARY outcome
Timeframe: up to 14 days after randomizationdefined by the proportion of patients who were delirium free at 14 days after randomization
Outcome measures
| Measure |
Flumazenil Group
n=10 Participants
The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Flumazenil
|
Placebo Group
n=10 Participants
The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Placebo: 0.9% normal saline
|
|---|---|---|
|
Number of Participants With Delirium Resolution
|
9 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: duration of admission to the intensive care unitlength of time that the patient was admitted to an intensive care unit service during the hospital stay
Outcome measures
| Measure |
Flumazenil Group
n=10 Participants
The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Flumazenil
|
Placebo Group
n=10 Participants
The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Placebo: 0.9% normal saline
|
|---|---|---|
|
Intensive Care Unit Length of Stay
|
7.8 days
Standard Deviation 4.8
|
7 days
Standard Deviation 6
|
SECONDARY outcome
Timeframe: up to 28 days after randomizationnumber of days within the first 28 days after enrollment that the patient was free from needing mechanical ventilation
Outcome measures
| Measure |
Flumazenil Group
n=10 Participants
The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Flumazenil
|
Placebo Group
n=10 Participants
The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Placebo: 0.9% normal saline
|
|---|---|---|
|
Number of Mechanical Ventilator Free Days
|
23.6 days
Standard Deviation 4.4
|
24.9 days
Standard Deviation 5
|
SECONDARY outcome
Timeframe: up to 72 hours after the start of the infusionnumber of times that a RASS score of + 2 to +4 occurred that did not resolve with decreasing study infusion
Outcome measures
| Measure |
Flumazenil Group
n=10 Participants
The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Flumazenil
|
Placebo Group
n=10 Participants
The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Placebo: 0.9% normal saline
|
|---|---|---|
|
Occurrence of Agitation Requiring Use of Rescue Sedatives While on Study Infusion
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 72 hours after the start of the infusionaverage duration of time patient was randomized to each infusion up to 72 hours
Outcome measures
| Measure |
Flumazenil Group
n=10 Participants
The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Flumazenil
|
Placebo Group
n=10 Participants
The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Placebo: 0.9% normal saline
|
|---|---|---|
|
Average Duration of Study Infusion
|
54.8 hours
Standard Deviation 16.8
|
58.2 hours
Standard Deviation 23.5
|
SECONDARY outcome
Timeframe: up to 72 hours after the start of the infusionaverage maximum rate (ml/hr) during the 72 hours after study infusion
Outcome measures
| Measure |
Flumazenil Group
n=10 Participants
The flumazenil continuous infusion is started at an initial dose of 0.1 mg/hr., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Flumazenil
|
Placebo Group
n=10 Participants
The placebo continuous infusion is started at an initial dose of 0.1 mg/hr (2 ml/hr)., and can be titrated up to a maximum of 0.3 mg/hr. Dose titrations may occur every 60 minutes to maintain RASS scores of 0 to +1. The maximum rate is 0.3 mg/hr.
Placebo: 0.9% normal saline
|
|---|---|---|
|
Average Maximum Rate of Study Infusion
|
5 milliliters per hour
Standard Deviation 2
|
5.2 milliliters per hour
Standard Deviation 2
|
Adverse Events
Flumazenil Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 1 deaths
Placebo Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Kendra Schomer, PharmD
University of California Davis Medical Center
Phone: 916-734-2243
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place