Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 14GRNT20010002 | Other Grant/Funding Number | American Heart Association |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Pittsburgh Medical Center | OTHER |
| Brigham and Women's Hospital | OTHER |
| University of Alabama at Birmingham | OTHER |
| Beaumont Hospital |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rocuronium | Experimental | 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). |
|
| Usual Care | Placebo Comparator | Patients will receive 100 mL of normal saline over 5-10 minutes at the beginning of the study in addition to usual care. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rocuronium | Drug | Neuromuscular Blockade |
| |
| Normal Saline |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Lactate Over 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. | 24 hours |
| Change in Lactate Over 24 Hours: Effect Estimate | Interaction between allocated treatment and time: ratio of geometric mean differences over 24 hours in log lactate values between the two groups. | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Time ROSC to Target Temperature | Time from return of spontaneous circulation to target temperature | Duration of hospitalization, limit 180 days |
| Length of Intensive Care Unit (ICU) Stay | Length of stay in ICU |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Michael W Donnino, MD | Beth Israel Deaconess Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Michael Kurz | Birmingham | Alabama | 35294 | United States | ||
| Beth Israel Deaconess Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32851921 | Derived | Moskowitz A, Andersen LW, Rittenberger JC, Swor R, Seethala RR, Kurz MC, Berg KM, Chase M, Cocchi MN, Grossestreuer AV, Liu X, Holmberg MJ, Callaway CW, Donnino MW. Continuous Neuromuscular Blockade Following Successful Resuscitation From Cardiac Arrest: A Randomized Trial. J Am Heart Assoc. 2020 Sep;9(17):e017171. doi: 10.1161/JAHA.120.017171. Epub 2020 Aug 27. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Of 818 patients assessed for eligibility, 83 met inclusion criteria and were randomized to treatment.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Lactate Over 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. | Posted | Number | mmol/L | 24 hours |
|
From time of enrollment to time of discharge, an average of 7.2 days.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mike Donnino | BIDMC | 6177542882 | mdonnino@bidmc.harvard.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 7, 2019 | Jun 7, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Jun 7, 2019 | Jun 28, 2020 | Prot_001.pdf |
Not provided
| ID | Term |
|---|---|
| D006323 | Heart Arrest |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077123 | Rocuronium |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000732 | Androstanols |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
Not provided
Not provided
| OTHER |
Not provided
Not provided
Not provided
Not provided
| Drug |
Normal Saline |
|
| Length of Stay Truncated at 28 Days |
| Mechanical Ventilation Duration | Mechanical Ventilation Duration in Hours | Duration of hospitalization, limit 180 days |
| Survival | In-hospital survival | Duration of hospitalization, limit 180 days |
| Number of Participants With Rankin Score ≤3 | 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:
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) | Duration of hospitalization, limit 180 days |
| Muscle Weakness Score | 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 | Duration of hospitalization, limit 180 days |
| Boston |
| Massachusetts |
| 02215 |
| United States |
| Brigham and Women's Hospital | Boston | Massachusetts | 02215 | United States |
| Robert Swor | Royal Oak | Michigan | 48073 | United States |
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| BG001 | 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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Past Medical History: Congestive Heart Failure | Count of Participants | Participants |
|
| Past Medical History: Atrial Fibrillation | Count of Participants | Participants |
|
| Past Medical History: Coronary Artery Disease | Count of Participants | Participants |
|
| Past Medical History: Prior Cardiac Arrest | Count of Participants | Participants |
|
| Past Medical History: Chronic Pulmonary Disease | Count of Participants | Participants |
|
| Past Medical History: Liver Cirrhosis | Count of Participants | Participants |
|
| Past Medical History: Kidney Disease | Count of Participants | Participants |
|
| Past Medical History: Active Malignancy | Count of Participants | Participants |
|
| Arrest Characteristics: Location (n, % Out of Hospital Cardiac Arrest) | Count of Participants | Participants |
|
| Arrest Characteristics: Initial Rhythm (n, % Shockable) | Count of Participants | Participants |
|
| Arrest Characteristics: Estimated Low-Flow Time (minutes, median, IQR) | Median | Inter-Quartile Range | minutes |
|
| Arrest Characteristics: Witnessed (n, % yes) | Count of Participants | Participants |
|
| Arrest Characteristics: Bystander Cardipulmonary Resuscitation (CPR) Provided (n, % yes) | Count of Participants | Participants |
|
| Arrest Characteristics: Arrest Etiology (n, % cardiac) | Count of Participants | Participants |
|
| Characteristics at Enrollment: Time from ROSC to Study Drug (hours, median, IQR) | Median | Inter-Quartile Range | hours |
|
| Characteristics at Enrollment: pH (median, IQR) | Median | Inter-Quartile Range | pH |
|
| Characteristics at Enrollment: Partial Pressure of Carbon Dioxide (pCO2) median, IQR | Median | Inter-Quartile Range | mmHg |
|
| Characteristics at Enrollment: Partial Pressure of Oxygen (pO2) median, IQR | Median | Inter-Quartile Range | mmHg |
|
| Characteristics at Enrollment: Shock Stratification (n, % shock) | Shock stratification (n, %) refers to the number and percent of patients in each arm who were on vasopressors at the time of enrollment and therefore were considered to be in shock. | Count of Participants | Participants |
|
| Characteristics at Enrollment: S-T Elevation Myocardial Infarction (STEMI) present (n, % yes) | Count of Participants | Participants |
|
| Characteristics at Enrollment: Target temperature (median, IQR) | Median | Inter-Quartile Range | celsius |
|
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
|
|
| Primary | Change in Lactate Over 24 Hours: Effect Estimate | Interaction between allocated treatment and time: ratio of geometric mean differences over 24 hours in log lactate values between the two groups. | Posted | Number | 95% Confidence Interval | Ratio | 24 hours |
|
|
|
| Secondary | Time ROSC to Target Temperature | Time from return of spontaneous circulation to target temperature | Posted | Median | Inter-Quartile Range | Hours | Duration of hospitalization, limit 180 days |
|
|
|
|
| Secondary | Length of Intensive Care Unit (ICU) Stay | Length of stay in ICU | ICU survivors row include only the 14 patients in each arm who survived to ICU discharge (n=14 in each arm). | Posted | Median | Inter-Quartile Range | days | Length of Stay Truncated at 28 Days |
|
|
|
|
| Secondary | Mechanical Ventilation Duration | Mechanical Ventilation Duration in Hours | 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. | Posted | Median | Inter-Quartile Range | Hours | Duration of hospitalization, limit 180 days |
|
|
|
|
| Secondary | Survival | In-hospital survival | Posted | Count of Participants | Participants | Duration of hospitalization, limit 180 days |
|
|
|
|
| Secondary | Number of Participants With Rankin Score ≤3 | 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:
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) | Posted | Count of Participants | Participants | Duration of hospitalization, limit 180 days |
|
|
|
|
| Secondary | Muscle Weakness Score | 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 | Posted | Median | Inter-Quartile Range | Points | Duration of hospitalization, limit 180 days |
|
|
|
| 23 |
| 37 |
| 0 |
| 37 |
| 0 |
| 37 |
| EG001 | 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 | 29 | 43 | 0 | 43 | 0 | 43 |
Not provided
Not provided
| D011083 |
| Polycyclic Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| ICU survivors |
|
|
| ICU survivors alone analyzed (n = 14 in each arm) | Negative binomial regression | 0.35 | Incidence rate ratio | 1.3 | 2-Sided | 95 | 0.8 | 2.0 | Equivalence | 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) |
| Anaysis for the patients surviving to extubation (n= 14 in both groups) | Regression, Linear | Duration log transformed and so parameter estimate represents geometric mean difference. | 0.32 | Geometric mean difference | 1.4 | 2-Sided | 95 | 0.7 | 2.9 | Equivalence | 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. |