Reevaluation Of Systemic Early Neuromuscular Blockade
- Conditions
- Acute Respiratory Distress Syndrome
- Interventions
- Registration Number
- NCT02509078
- Lead Sponsor
- Massachusetts General Hospital
- Brief Summary
This study evaluates whether giving a neuromuscular blocker (skeletal muscle relaxant) to a patient with acute respiratory distress syndrome will improve survival. Half of the patients will receive a neuromuscular blocker for two days and in the other half the use of neuromuscular blockers will be discouraged.
- Detailed Description
PRIMARY OBJECTIVE:
To assess the efficacy and safety of early neuromuscular blockade in reducing mortality and morbidity in patients with moderate-severe ARDS, in comparison to a control group with no routine early neuromuscular blockade (NMB).
PRIMARY HYPOTHESIS:
Early neuromuscular blockade will improve mortality prior to discharge home before day 90, in patients with moderate-severe ARDS.
The trial will accrue a maximum of 1408 patients. Patients will be recruited from the emergency departments, intensive care units and other acute care areas of the PETAL Network Clinical Centers and randomized to the active (NMB) or control. The overall strategy is to screen, consent, and enroll early, every newly intubated, acutely ill or post-operative, eligible patient at each site, using clinically obtained pulse oximetry and blood gases.
By preventing active expiration, and/or patient ventilator dyssynchrony, neuromuscular blockade may create a more homogenous distribution of airway pressures and tidal volumes, preventing barotrauma/volutrauma and "atelectrauma" resulting in less ventilator-induced lung injury.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1008
Not provided
- Lack of informed consent
- Continuous neuromuscular blockade at enrollment
- Known pregnancy
- Currently receiving ECMO therapy
- Chronic respiratory failure defined as PaCO2 > 60 mm Hg in the outpatient setting
- Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing
- Actual body weight exceeding 1 kg per centimeter of height
- Severe chronic liver disease defined as a Child-Pugh score of 12-15 (Appendix A2)
- Bone marrow transplantation within the last 1 year
- Expected duration of mechanical ventilation of < 48 hours
- Decision to withhold life-sustaining treatment; except in those patients committed to full support except cardiopulmonary resuscitation if an actual cardiac arrest occurs
- Moribund patient not expected to survive 24 hours; if CPR provided, assess for moribund status greater than 6 from CPR conclusion
- Diffuse alveolar hemorrhage from vasculitis
- Burns > 70% total body surface
- Unwillingness to utilize the ARDS Network 6 ml/kg IBW ventilation protocol
- Previous hypersensitivity or anaphylactic reaction to cisatracurium
- Neuromuscular conditions that may potentiate neuromuscular blockade and/or impair spontaneous ventilation (Appendix A2)
- Neurologic conditions undergoing treatment for intracranial hypertension
- Enrollment in an interventional ARDS trial with direct impact on neuromuscular blockade and PEEP
- >120 hours of mechanical ventilation
- P/F < 200 mmHg at the time of randomization (if available)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Early Neuromuscular Blockade (NMB) Cisatracurium Besylate Patients will receive cisatracurium besylate for the first 48 hours of the trial.
- Primary Outcome Measures
Name Time Method Hospital Mortality to Day 90 90 days after randomization The percentage of subjects alive at study day 90. Those subjects discharged home prior to day 90 were counted as alive at day 90.
- Secondary Outcome Measures
Name Time Method Mean Organ Failure Free Days to Day 28 28 days after randomization SOFA (Sepsis-related Organ Failure Assessment) was used to determine criteria for an organ failure free day. Scores were based on four of the six SOFA organ categories: Coagulation, Liver, Cardiovascular, and Renal. Each category was scored 0-4; 0 being normal functioning and 4 being the most abnormal. A patient was considered failure free on each day alive with SOFA scores below 2 for all four organ systems.
Ref: Vincent, J.L., et al., The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med, 1996. 22(7): p. 707-10.ICU Free Days to Day 28 28 days after randomization ICU free days is defined as the number of days between randomization and day 28 in which the patient is in the ICU (for any part of a day).
EuroQol (EQ-5D-5L): Health Related Quality of Life 12 months after randomization Using a standardized scale, do health reasons limit the person's ability to enjoy their life? Pooled estimates from patient survey and proxy survey were used. Utility index was computed from a lookup table according to EQ-5D-5L response profiles; utility index ranges from -0.11 to 1.00 (higher scores are better; 1.00 is perfect health), minimal clinically important difference (MCID) is 0.07
Mean Hospital Free Days to Days 28 28 days after randomization Hospital free days are days alive post hospital discharge through day 28. Patients who die on or prior to day 28 are assigned zero hospital free days.
Mean Ventilator Free Days to Day 28 28 days after randomization Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days.
Katz Activities of Daily Living (ADL)/Lawton Instrumental Activities Of Daily Living Scale (IADL) 12 months after randomization Assesses whether individual can living independently and assess a range of common functional activities, from walking and toileting to managing money and cooking meals. Data is a pooled estimates from patient survey and proxy survey. The total score is rated from 0 to 10 (MCID=1; 1 point=1 ADL); a higher score indicates having more difficulties in daily activities.
PTSS-14: Post-traumatic Stress-like Symptoms Scores >/= 45 12 months after randomization Does the patient have symptoms of anxiety and stress from their ICU stay? PTSS-14 is only asked at month 6 and month 12 in patient survey; total score is rated from 14 to 98 and a higher score indicates having more post-traumatic stress syndrome related symptoms. Participants with scores greater than or equal to 45 were reported.
MoCA-Blind: Montreal Cognitive Assessment 12 months after randomization How clearly can patient think and recall things? MoCA-Blind is only asked in patient survey; total score is rated from 0 to 30 and a higher score indicates better cognitive performance. Normal range:
26 or greater.
Trial Locations
- Locations (44)
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Wesley Long Hospital
🇺🇸Greensboro, North Carolina, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
UCSF Fresno
🇺🇸Fresno, California, United States
University or Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
VCU Medical Center
🇺🇸Richmond, Virginia, United States
UPMC Presbyterian/Mercy/Shadyside
🇺🇸Pittsburgh, Pennsylvania, United States
Indiana University Methodist Hospital
🇺🇸Indianapolis, Indiana, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Swedish Hospital First Hill
🇺🇸Seattle, Washington, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Medical Center of Aurora
🇺🇸Aurora, Colorado, United States
Denver Health Medical Center
🇺🇸Denver, Colorado, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
Stanford University Hospital
🇺🇸Stanford, California, United States
Summa Akron City Hospital
🇺🇸Akron, Ohio, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Utah Valley Regional Medical Center
🇺🇸Provo, Utah, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
University Medical Center
🇺🇸New Orleans, Louisiana, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
St. Vincent's Hospital
🇺🇸Worcester, Massachusetts, United States
Henry Ford Medical Center
🇺🇸Detroit, Michigan, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
McKay-Dee Hospital
🇺🇸Ogden, Utah, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
University Hospital
🇺🇸Salt Lake City, Utah, United States
Mt. Sinai Hospital
🇺🇸New York, New York, United States
Swedish Hospital Cherry Hill
🇺🇸Seattle, Washington, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States