NMB_in_CA: Neuromuscular Blockade for Post-Cardiac Arrest Care
Sponsor
Beth Israel Deaconess Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT02260258
Collaborator
University of Pittsburgh Medical Center (Other), Brigham and Women's Hospital (Other), University of Alabama at Birmingham (Other), Beaumont Hospital (Other)
83
5
2
55.9
16.6
0.3
Study Details
Study Description
Brief Summary
The main purpose of this study is to evaluate if neuromuscular blockade improves lactate clearance (and preliminary secondary clinical outcome measures) as compared to usual care in post-cardiac arrest patients undergoing targeted temperature management.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Out-of-hospital cardiac arrest (OHCA) occurs in more than 300,000 patients in the United States each year with an estimated mortality of greater than 90%. Unfortunately, we currently have little to offer in terms of treatment other than supportive care for the post-cardiac arrest patient. Neuromuscular blockade (NMB) is sometimes utilized in post-arrest patients particularly for the prevention of shivering. However, usage of NMB remains controversial and current American Heart Association (AHA) recommendations are to minimize utilization. Recent prospective randomized trials in patients with acute respiratory distress syndrome suggest a mortality benefit from NMB and an excellent safety profile. Furthermore, observational trials in both sepsis and post-cardiac arrest show that the use of NMB is associated with improved survival. Given this, we hypothesize that continuous NMB will be beneficial in post-arrest patients. In order to test this hypothesis, we propose a multi-center, randomized, open-label, phase II trial in post-CA patients comparing sustained NMB administration for 24 hours to standard of care after return of spontaenous circulation (ROSC). We will enroll adult, comatose OHCA patients with ROSC and will utilize an already existing clinical trials network for the completion of the study. Patients will be randomized to receive either rocuronium for 24 hours or to receive placebo with usual care. Previous data from our group has suggested that lactate levels in the post-arrest patient are a good surrogate marker for mortality. We have therefore chosen to utilize lactate levels at 24 hours as the primary endpoint for the current trial. Secondarily we will evaluate clinical endpoints including length of stay (LOS), in-hospital mortality, and good neurological outcome. We will perform a sub-study of inflammatory markers and oxygen consumption.
Study Design
Study Type:
Interventional
Actual Enrollment
:
83 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Other
Official Title:
Neuromuscular Blockade for Post-Cardiac Arrest Care
Study Start Date
:
Oct 1, 2014
Actual Primary Completion Date
:
May 29, 2019
Actual Study Completion Date
:
May 29, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Rocuronium Patients will receive a bolus dose of 1 mg/kg, then a continuous intravenous (IV) 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). |
Drug: Rocuronium
Neuromuscular Blockade
|
| Placebo Comparator: 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. |
Drug: Normal Saline
Normal Saline
|
Outcome Measures
Primary Outcome Measures
- Change in Lactate Over 24 Hours [24 hours]
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.
- Change in Lactate Over 24 Hours: Effect Estimate [24 hours]
Interaction between allocated treatment and time: ratio of geometric mean differences over 24 hours in log lactate values between the two groups.
Secondary Outcome Measures
- Time ROSC to Target Temperature [Duration of hospitalization, limit 180 days]
Time from return of spontaneous circulation to target temperature
- Length of Intensive Care Unit (ICU) Stay [Length of Stay Truncated at 28 Days]
Length of stay in ICU
- Mechanical Ventilation Duration [Duration of hospitalization, limit 180 days]
Mechanical Ventilation Duration in Hours
- Survival [Duration of hospitalization, limit 180 days]
In-hospital survival
- Number of Participants With Rankin Score ≤3 [Duration of hospitalization, limit 180 days]
Modified 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)
- Muscle Weakness Score [Duration of hospitalization, limit 180 days]
Medical 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
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Adult (≥ 18 years)
-
Cardiac arrest with sustained return of spontaneous circulation (ROSC)
-
Comatose (i.e., not following commands) following ROSC
-
Undergoing targeted temperature management (TTM)
-
Time of enrollment ≤ 6 hours from initiation of targeted temperature management
-
Serum Lactate ≥2
Exclusion Criteria:
-
Pre-existing dementia, severe brain injury, or dependence on others for activities of daily living (i.e. a modified Rankin scale (mRS) score of 4 or higher)
-
Traumatic etiology of the cardiac arrest
-
Protected population (pregnant, prisoner)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Michael Kurz | Birmingham | Alabama | United States | 35294 |
| 2 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 3 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02215 |
| 4 | Robert Swor | Royal Oak | Michigan | United States | 48073 |
| 5 | University of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15213 |
Sponsors and Collaborators
- Beth Israel Deaconess Medical Center
- University of Pittsburgh Medical Center
- Brigham and Women's Hospital
- University of Alabama at Birmingham
- Beaumont Hospital
Investigators
- Principal Investigator: Michael W Donnino, MD, Beth Israel Deaconess Medical Center
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Michael Donnino,
Michael Donnino MD,
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT02260258
Other Study ID Numbers:
- 2014P000204
- 14GRNT20010002
First Posted:
Oct 9, 2014
Last Update Posted:
Jan 29, 2021
Last Verified:
Jan 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Keywords provided by Michael Donnino,
Michael Donnino MD,
Beth Israel Deaconess Medical Center
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 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. |
|---|---|
| Pre-assignment Detail | Of 818 patients assessed for eligibility, 83 met inclusion criteria and were randomized to treatment. |
| Arm/Group Title | Rocuronium | Usual Care |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Period Title: Overall Study | ||
| STARTED | 39 | 44 |
| COMPLETED | 37 | 43 |
| NOT COMPLETED | 2 | 1 |
Baseline Characteristics
| Arm/Group Title | Rocuronium | Usual Care | Total |
|---|---|---|---|
| Arm/Group Description | 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 | 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 of all reporting groups |
| Overall Participants | 37 | 43 | 80 |
| Age (years) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [years] |
66
|
64
|
65
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
17
45.9%
|
14
32.6%
|
31
38.8%
|
| Male |
20
54.1%
|
29
67.4%
|
49
61.3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Race (n, % White) |
20
54.1%
|
22
51.2%
|
42
52.5%
|
| Race (n, % Black/African-American) |
7
18.9%
|
12
27.9%
|
19
23.8%
|
| Race (n, % Asian) |
1
2.7%
|
0
0%
|
1
1.3%
|
| Race (n, % American Indian/Native Alaskan) |
1
2.7%
|
0
0%
|
1
1.3%
|
| Race (n, % Other) |
2
5.4%
|
0
0%
|
2
2.5%
|
| Race (n, % Unknown/Not Reported) |
6
16.2%
|
9
20.9%
|
15
18.8%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
37
100%
|
43
100%
|
80
100%
|
| Past Medical History: Congestive Heart Failure (Count of Participants) | |||
| Count of Participants [Participants] |
9
24.3%
|
12
27.9%
|
21
26.3%
|
| Past Medical History: Atrial Fibrillation (Count of Participants) | |||
| Count of Participants [Participants] |
7
18.9%
|
9
20.9%
|
16
20%
|
| Past Medical History: Coronary Artery Disease (Count of Participants) | |||
| Count of Participants [Participants] |
14
37.8%
|
9
20.9%
|
23
28.8%
|
| Past Medical History: Prior Cardiac Arrest (Count of Participants) | |||
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
| Past Medical History: Chronic Pulmonary Disease (Count of Participants) | |||
| Count of Participants [Participants] |
12
32.4%
|
9
20.9%
|
21
26.3%
|
| Past Medical History: Liver Cirrhosis (Count of Participants) | |||
| Count of Participants [Participants] |
1
2.7%
|
2
4.7%
|
3
3.8%
|
| Past Medical History: Kidney Disease (Count of Participants) | |||
| Count of Participants [Participants] |
9
24.3%
|
14
32.6%
|
23
28.8%
|
| Past Medical History: Active Malignancy (Count of Participants) | |||
| Count of Participants [Participants] |
3
8.1%
|
2
4.7%
|
5
6.3%
|
| Arrest Characteristics: Location (n, % Out of Hospital Cardiac Arrest) (Count of Participants) | |||
| Count of Participants [Participants] |
35
94.6%
|
40
93%
|
75
93.8%
|
| Arrest Characteristics: Initial Rhythm (n, % Shockable) (Count of Participants) | |||
| Count of Participants [Participants] |
17
45.9%
|
16
37.2%
|
33
41.3%
|
| Arrest Characteristics: Estimated Low-Flow Time (minutes, median, IQR) (minutes) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [minutes] |
4
|
2
|
3
|
| Arrest Characteristics: Witnessed (n, % yes) (Count of Participants) | |||
| Count of Participants [Participants] |
27
73%
|
26
60.5%
|
53
66.3%
|
| Arrest Characteristics: Bystander Cardipulmonary Resuscitation (CPR) Provided (n, % yes) (Count of Participants) | |||
| Count of Participants [Participants] |
24
64.9%
|
26
60.5%
|
50
62.5%
|
| Arrest Characteristics: Arrest Etiology (n, % cardiac) (Count of Participants) | |||
| Count of Participants [Participants] |
27
73%
|
30
69.8%
|
57
71.3%
|
| Characteristics at Enrollment: Time from ROSC to Study Drug (hours, median, IQR) (hours) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [hours] |
7.5
|
6.3
|
6.5
|
| Characteristics at Enrollment: pH (median, IQR) (pH) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [pH] |
7.3
|
7.3
|
7.3
|
| Characteristics at Enrollment: Partial Pressure of Carbon Dioxide (pCO2) median, IQR (mmHg) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [mmHg] |
41.5
|
40.0
|
41.5
|
| Characteristics at Enrollment: Partial Pressure of Oxygen (pO2) median, IQR (mmHg) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [mmHg] |
100.0
|
161.0
|
132.5
|
| Characteristics at Enrollment: Shock Stratification (n, % shock) (Count of Participants) | |||
| Count of Participants [Participants] |
19
51.4%
|
21
48.8%
|
40
50%
|
| Characteristics at Enrollment: S-T Elevation Myocardial Infarction (STEMI) present (n, % yes) (Count of Participants) | |||
| Count of Participants [Participants] |
4
10.8%
|
6
14%
|
10
12.5%
|
| Characteristics at Enrollment: Target temperature (median, IQR) (celsius) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [celsius] |
35
|
34
|
35
|
Outcome Measures
| Title | Change in Lactate Over 24 Hours |
|---|---|
| Description | 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. |
| Time Frame | 24 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rocuronium | Usual Care |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 37 | 43 |
| Number [mmol/L] |
-2.2
|
-2.3
|
| Title | Change in Lactate Over 24 Hours: Effect Estimate |
|---|---|
| Description | Interaction between allocated treatment and time: ratio of geometric mean differences over 24 hours in log lactate values between the two groups. |
| Time Frame | 24 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Effect Estimate |
|---|---|
| Arm/Group Description | Value of the interaction term between allocated treatment and time, which is presented as a ratio of geometric mean differences over 24 hours. Values above 1.0 favor the placebo arm. |
| Measure Participants | 80 |
| Number (95% Confidence Interval) [Ratio] |
1.3
|
| Title | Time ROSC to Target Temperature |
|---|---|
| Description | Time from return of spontaneous circulation to target temperature |
| Time Frame | Duration of hospitalization, limit 180 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rocuronium | Usual Care |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 37 | 43 |
| Median (Inter-Quartile Range) [Hours] |
6.8
|
8.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rocuronium, Usual Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Time variable log transformed and compared using linear regression controlling for shock stratification and site. Effect estimate represents geometric mean difference. Values above 1.0 favor longer duration in the NMB arm. | |
| Statistical Test of Hypothesis | p-Value | 0.82 |
| Comments | A priori threshold for significance 0.05 | |
| Method | Regression, Linear | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean difference |
| Estimated Value | 1 | |
| Confidence Interval |
(2-Sided) 95% 0.7 to 1.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Length of Intensive Care Unit (ICU) Stay |
|---|---|
| Description | Length of stay in ICU |
| Time Frame | Length of Stay Truncated at 28 Days |
Outcome Measure Data
| Analysis Population Description |
|---|
| ICU survivors row include only the 14 patients in each arm who survived to ICU discharge (n=14 in each arm). |
| Arm/Group Title | Rocuronium | Usual Care |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 37 | 43 |
| All patients |
6.0
|
4.0
|
| ICU survivors |
9.0
|
5.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rocuronium, Usual Care |
|---|---|---|
| Comments | All patients analyzed (N = 37 in NMB and 43 in Usual Care) | |
| Type of Statistical Test | Equivalence | |
| Comments | LOS truncated at 28 days and compared using negative binomial regression controlling for stratification and site. Effect estimates represent incidence rate ratios. The parameter estimate, p value and CI provided below are from the negative binomial regression carried out all patients (N = 37 in NMB and 43 in Usual Care) | |
| Statistical Test of Hypothesis | p-Value | 0.09 |
| Comments | ||
| Method | Negative binomial regression | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Incidence rate ratio |
| Estimated Value | 1.4 | |
| Confidence Interval |
(2-Sided) 95% 1.0 to 1.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Rocuronium, Usual Care |
|---|---|---|
| Comments | ICU survivors alone analyzed (n = 14 in each arm) | |
| Type of Statistical Test | Equivalence | |
| Comments | LOS truncated at 28 days and compared using negative binomial regression controlling for stratification and site. Effect estimates represent incidence rate ratios. The parameter estimate, p value and CI provided below are from the negative binomial regression carried out on ICU survivors alone (n = 14 in NMB and 14 in Control) | |
| Statistical Test of Hypothesis | p-Value | 0.35 |
| Comments | ||
| Method | Negative binomial regression | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Incidence rate ratio |
| Estimated Value | 1.3 | |
| Confidence Interval |
(2-Sided) 95% 0.8 to 2.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Mechanical Ventilation Duration |
|---|---|
| Description | Mechanical Ventilation Duration in Hours |
| Time Frame | Duration of hospitalization, limit 180 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Rocuronium | Usual Care |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 37 | 43 |
| All patients |
102.0
|
82.7
|
| Survivors to extubation |
126.3
|
66.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rocuronium, Usual Care |
|---|---|---|
| Comments | Anaysis for the full data (n= 37 in NMB and 43 in Control) | |
| Type of Statistical Test | Equivalence | |
| Comments | Duration log transformed and compared using linear regression controlling for shock stratification and site. Includes all patients (n=37 in NMB and n = 43 in control). Effect estimates represent geometric mean difference. Values above 1.0 favor longer duration in the NMB arm. | |
| Statistical Test of Hypothesis | p-Value | 0.18 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | Duration log transformed and so parameter estimate represents geometric mean difference. | |
| Method of Estimation | Estimation Parameter | Geometric mean difference |
| Estimated Value | 1.3 | |
| Confidence Interval |
(2-Sided) 95% 0.9 to 1.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Rocuronium, Usual Care |
|---|---|---|
| Comments | Anaysis for the patients surviving to extubation (n= 14 in both groups) | |
| Type of Statistical Test | Equivalence | |
| Comments | Duration log transformed and compared using linear regression controlling for shock stratification and site. Includes 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. Effect estimates represent geometric mean difference. Values above 1.0 favor longer duration in the NMB arm. | |
| Statistical Test of Hypothesis | p-Value | 0.32 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | Duration log transformed and so parameter estimate represents geometric mean difference. | |
| Method of Estimation | Estimation Parameter | Geometric mean difference |
| Estimated Value | 1.4 | |
| Confidence Interval |
(2-Sided) 95% 0.7 to 2.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Survival |
|---|---|
| Description | In-hospital survival |
| Time Frame | Duration of hospitalization, limit 180 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rocuronium | Usual Care |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 37 | 43 |
| Count of Participants [Participants] |
14
37.8%
|
14
32.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rocuronium, Usual Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Comparison made using logistic regression controlling for shock stratification and site. Effect estimates represent odds ratios | |
| Statistical Test of Hypothesis | p-Value | 0.63 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.3 | |
| Confidence Interval |
(2-Sided) 95% 0.5 to 3.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Rankin Score ≤3 |
|---|---|
| Description | Modified 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) |
| Time Frame | Duration of hospitalization, limit 180 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rocuronium | Usual Care |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 37 | 43 |
| Count of Participants [Participants] |
11
29.7%
|
9
20.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rocuronium, Usual Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Comparison made using logistic regression controlling for shock stratification and site. Effect estimates represent odds ratios | |
| Statistical Test of Hypothesis | p-Value | 0.35 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.7 | |
| Confidence Interval |
(2-Sided) 95% 0.6 to 4.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Muscle Weakness Score |
|---|---|
| Description | Medical 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 |
| Time Frame | Duration of hospitalization, limit 180 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rocuronium | Usual Care |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 37 | 43 |
| Median (Inter-Quartile Range) [Points] |
30
|
30
|
Adverse Events
| Time Frame | From time of enrollment to time of discharge, an average of 7.2 days. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Rocuronium | Usual Care | ||
| Arm/Group Description | 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 | 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 | ||
All Cause Mortality |
||||
| Rocuronium | Usual Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 23/37 (62.2%) | 29/43 (67.4%) | ||
Serious Adverse Events |
||||
| Rocuronium | Usual Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/37 (0%) | 0/43 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Rocuronium | Usual Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/37 (0%) | 0/43 (0%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Mike Donnino |
|---|---|
| Organization | BIDMC |
| Phone | 6177542882 |
| mdonnino@bidmc.harvard.edu |
Responsible Party:
Michael Donnino,
Michael Donnino MD,
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT02260258
Other Study ID Numbers:
- 2014P000204
- 14GRNT20010002
First Posted:
Oct 9, 2014
Last Update Posted:
Jan 29, 2021
Last Verified:
Jan 1, 2021