Trial Outcomes & Findings for Neuromuscular Blockade for Post-Cardiac Arrest Care (NCT NCT02260258)
NCT ID: NCT02260258
Last Updated: 2021-01-29
Results Overview
Change in median serum lactate level between enrollment and 24-hours after the receipt of study drug. A negative number indicates that the lactate levels were lower at 24 hours compared to their level at receipt of study drug.
COMPLETED
PHASE2
83 participants
24 hours
2021-01-29
Participant Flow
Between December 2014 and May 2019, we recruited adult patients (aged ≥18 years) who experienced a cardiac arrest and subsequently had sustained ROSC (≥20 minutes) but remained unresponsive and were undergoing TTM between 32℃ and 36℃. We added an additional inclusion criterion of a minimum serum lactate level of ≥2mmol/L early in study enrollment.
Of 818 patients assessed for eligibility, 83 met inclusion criteria and were randomized to treatment.
Participant milestones
| Measure |
Rocuronium
Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
Rocuronium: Neuromuscular Blockade
|
Usual Care
Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
Normal Saline: Normal Saline
|
|---|---|---|
|
Overall Study
STARTED
|
39
|
44
|
|
Overall Study
COMPLETED
|
37
|
43
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Rocuronium
Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
Rocuronium: Neuromuscular Blockade
|
Usual Care
Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
Normal Saline: Normal Saline
|
|---|---|---|
|
Overall Study
2 patients in NMB arm and 1 in control arm had clinical changes that precluded drug administration
|
2
|
1
|
Baseline Characteristics
Neuromuscular Blockade for Post-Cardiac Arrest Care
Baseline characteristics by cohort
| Measure |
Rocuronium
n=37 Participants
Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
Rocuronium: Neuromuscular Blockade
|
Usual Care
n=43 Participants
Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
Normal Saline: Normal Saline
|
Total
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
66 years
n=5 Participants
|
64 years
n=7 Participants
|
65 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race (n, % White)
|
20 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race (n, % Black/African-American)
|
7 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race (n, % Asian)
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race (n, % American Indian/Native Alaskan)
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race (n, % Other)
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race (n, % Unknown/Not Reported)
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
37 participants
n=5 Participants
|
43 participants
n=7 Participants
|
80 participants
n=5 Participants
|
|
Past Medical History: Congestive Heart Failure
|
9 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Past Medical History: Atrial Fibrillation
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Past Medical History: Coronary Artery Disease
|
14 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Past Medical History: Prior Cardiac Arrest
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Past Medical History: Chronic Pulmonary Disease
|
12 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Past Medical History: Liver Cirrhosis
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Past Medical History: Kidney Disease
|
9 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Past Medical History: Active Malignancy
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Arrest Characteristics: Location (n, % Out of Hospital Cardiac Arrest)
|
35 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
Arrest Characteristics: Initial Rhythm (n, % Shockable)
|
17 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Arrest Characteristics: Estimated Low-Flow Time (minutes, median, IQR)
|
4 minutes
n=5 Participants
|
2 minutes
n=7 Participants
|
3 minutes
n=5 Participants
|
|
Arrest Characteristics: Witnessed (n, % yes)
|
27 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Arrest Characteristics: Bystander Cardipulmonary Resuscitation (CPR) Provided (n, % yes)
|
24 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
|
Arrest Characteristics: Arrest Etiology (n, % cardiac)
|
27 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
|
Characteristics at Enrollment: Time from ROSC to Study Drug (hours, median, IQR)
|
7.5 hours
n=5 Participants
|
6.3 hours
n=7 Participants
|
6.5 hours
n=5 Participants
|
|
Characteristics at Enrollment: pH (median, IQR)
|
7.3 pH
n=5 Participants
|
7.3 pH
n=7 Participants
|
7.3 pH
n=5 Participants
|
|
Characteristics at Enrollment: Partial Pressure of Carbon Dioxide (pCO2) median, IQR
|
41.5 mmHg
n=5 Participants
|
40.0 mmHg
n=7 Participants
|
41.5 mmHg
n=5 Participants
|
|
Characteristics at Enrollment: Partial Pressure of Oxygen (pO2) median, IQR
|
100.0 mmHg
n=5 Participants
|
161.0 mmHg
n=7 Participants
|
132.5 mmHg
n=5 Participants
|
|
Characteristics at Enrollment: Shock Stratification (n, % shock)
|
19 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Characteristics at Enrollment: S-T Elevation Myocardial Infarction (STEMI) present (n, % yes)
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Characteristics at Enrollment: Target temperature (median, IQR)
|
35 celsius
n=5 Participants
|
34 celsius
n=7 Participants
|
35 celsius
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 hoursChange in median serum lactate level between enrollment and 24-hours after the receipt of study drug. A negative number indicates that the lactate levels were lower at 24 hours compared to their level at receipt of study drug.
Outcome measures
| Measure |
Rocuronium
n=37 Participants
Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
Rocuronium: Neuromuscular Blockade
|
Usual Care
n=43 Participants
Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
Normal Saline: Normal Saline
|
|---|---|---|
|
Change in Lactate Over 24 Hours
|
-2.2 mmol/L
|
-2.3 mmol/L
|
PRIMARY outcome
Timeframe: 24 hoursInteraction between allocated treatment and time: ratio of geometric mean differences over 24 hours in log lactate values between the two groups.
Outcome measures
| Measure |
Rocuronium
n=80 Participants
Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
Rocuronium: Neuromuscular Blockade
|
Usual Care
Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
Normal Saline: Normal Saline
|
|---|---|---|
|
Change in Lactate Over 24 Hours: Effect Estimate
|
1.3 Ratio
Interval 1.0 to 1.8
|
—
|
SECONDARY outcome
Timeframe: Duration of hospitalization, limit 180 daysTime from return of spontaneous circulation to target temperature
Outcome measures
| Measure |
Rocuronium
n=37 Participants
Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
Rocuronium: Neuromuscular Blockade
|
Usual Care
n=43 Participants
Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
Normal Saline: Normal Saline
|
|---|---|---|
|
Time ROSC to Target Temperature
|
6.8 Hours
Interval 5.3 to 9.4
|
8.3 Hours
Interval 4.7 to 11.2
|
SECONDARY outcome
Timeframe: Length of Stay Truncated at 28 DaysPopulation: ICU survivors row include only the 14 patients in each arm who survived to ICU discharge (n=14 in each arm).
Length of stay in ICU
Outcome measures
| Measure |
Rocuronium
n=37 Participants
Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
Rocuronium: Neuromuscular Blockade
|
Usual Care
n=43 Participants
Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
Normal Saline: Normal Saline
|
|---|---|---|
|
Length of Intensive Care Unit (ICU) Stay
All patients
|
6.0 days
Interval 3.0 to 11.0
|
4.0 days
Interval 3.0 to 7.0
|
|
Length of Intensive Care Unit (ICU) Stay
ICU survivors
|
9.0 days
Interval 6.0 to 16.0
|
5.0 days
Interval 4.0 to 12.0
|
SECONDARY outcome
Timeframe: Duration of hospitalization, limit 180 daysPopulation: Includes all patients, and also patients surviving to discontinuation of mechanical ventilation (n=14 in each group). Two patients discharged from the hospital on mechanical ventilation have duration truncated at time of discharge and are considered survivors to extubation.
Mechanical Ventilation Duration in Hours
Outcome measures
| Measure |
Rocuronium
n=37 Participants
Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
Rocuronium: Neuromuscular Blockade
|
Usual Care
n=43 Participants
Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
Normal Saline: Normal Saline
|
|---|---|---|
|
Mechanical Ventilation Duration
All patients
|
102.0 Hours
Interval 64.3 to 206.4
|
82.7 Hours
Interval 47.4 to 160.7
|
|
Mechanical Ventilation Duration
Survivors to extubation
|
126.3 Hours
Interval 76.1 to 280.6
|
66.9 Hours
Interval 55.6 to 172.7
|
SECONDARY outcome
Timeframe: Duration of hospitalization, limit 180 daysIn-hospital survival
Outcome measures
| Measure |
Rocuronium
n=37 Participants
Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
Rocuronium: Neuromuscular Blockade
|
Usual Care
n=43 Participants
Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
Normal Saline: Normal Saline
|
|---|---|---|
|
Survival
|
14 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: Duration of hospitalization, limit 180 daysModified Rankin scale to assess neurological outcome at discharge. The scale ranges from 0 to 6, and is used for measuring the performance of daily activities. The score is as follows: * 0: No symptoms * 1: No significant disability (able to carry out all usual activities, despite some symptoms) * 2: Slight disability (able to look after own affairs without assistance, but unable to carry out all previous activities) * 3: Moderate disability (requires some help, but able to walk unassisted) * 4: Moderately severe disability (unable to attend to own bodily needs without assistance, and unable to walk unassisted) * 5: Severe disability (requires constant nursing care and attention, bedridden, incontinent) * 6: Dead. Higher cores represent worse outcomes. Good and bad neurological outcome will be defined as a score of 0-3 and 4-6 respectively. This outcome reports the number of patients with a good neurological outcome( modified Rankin score ≤ 3)
Outcome measures
| Measure |
Rocuronium
n=37 Participants
Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
Rocuronium: Neuromuscular Blockade
|
Usual Care
n=43 Participants
Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
Normal Saline: Normal Saline
|
|---|---|---|
|
Number of Participants With Rankin Score ≤3
|
11 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: Duration of hospitalization, limit 180 daysMedical Research Council Scale : Measured for 6 muscle groups (3 in the upper limbs and 3 in the lower limbs). Maximum score is 30 (grade 5 for each group) and minimum is 0 (grade 0 for each group). If muscle group strength was not symmetric bilaterally, higher measurement used. Higher scores indicate better outcomes. Grade 5: Muscle contracts normally against full resistance. Grade 4: Muscle strength is reduced but muscle contraction can still move joint against resistance. Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed. Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane. Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle. Grade 0: No movement is observed
Outcome measures
| Measure |
Rocuronium
n=37 Participants
Patients will receive a bolus dose of 1 mg/kg, then a continuous I.V. infusion as per standard intensive care unit practice.
Of note, protocol allows for use of cistatracurium in place of rocuronium for either reasons of drug-shortage or clinical conditions (if institutional preferences for dose adjustment in liver or renal insufficiency arise).
Rocuronium: Neuromuscular Blockade
|
Usual Care
n=43 Participants
Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care.
Normal Saline: Normal Saline
|
|---|---|---|
|
Muscle Weakness Score
|
30 Points
Interval 28.0 to 30.0
|
30 Points
Interval 27.0 to 30.0
|
Adverse Events
Rocuronium
Usual Care
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place