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Reevaluation Of Systemic Early Neuromuscular Blockade (ROSE)

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ClinicalTrials.gov Identifier: NCT02509078
Recruitment Status : Completed
First Posted : July 27, 2015
Results First Posted : August 13, 2019
Last Update Posted : August 13, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Boyd Taylor Thompson, Massachusetts General Hospital

Study Description
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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.

Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Drug: Cisatracurium Besylate Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1008 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reevaluation Of Systemic Early Neuromuscular Blockade
Actual Study Start Date : January 4, 2016
Actual Primary Completion Date : July 3, 2018
Actual Study Completion Date : April 4, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Early Neuromuscular Blockade (NMB)
Patients will receive cisatracurium besylate for the first 48 hours of the trial.
 Drug: Cisatracurium Besylate
Patients randomized to the early neuromuscular blockade arm will receive a cisatracurium besylate bolus of 15 mg, followed by a continuous infusion of 37.5 mg/hour for 48 hours. Patients randomized to the control arm will receive no protocol specified neuromuscular blockade.
Other Name: Nimbex
No Intervention: Control: No Routine Early NMB
Use of non-study NMB will be discouraged.


Outcome Measures
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Primary Outcome Measures :
  1. Hospital Mortality to Day 90 [ Time Frame: 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 :
  1. Mean Ventilator Free Days to Day 28 [ Time Frame: 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.

  2. Mean Organ Failure Free Days to Day 28 [ Time Frame: 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.


  3. ICU Free Days to Day 28 [ Time Frame: 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).

  4. Mean Hospital Free Days to Days 28 [ Time Frame: 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.

  5. Katz Activities of Daily Living (ADL)/Lawton Instrumental Activities Of Daily Living Scale (IADL) [ Time Frame: 3 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.

  6. EuroQol (EQ-5D-5L): Health Related Quality of Life [ Time Frame: 3 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

  7. PTSS-14: Post-traumatic Stress-like Symptoms Scores >/= 45 [ Time Frame: 6 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.

  8. MoCA-Blind: Montreal Cognitive Assessment [ Time Frame: 3 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.

  9. Katz Activities of Daily Living (ADL)/Lawton Instrumental Activities Of Daily Living Scale (IADL) [ Time Frame: 6 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.

  10. Katz Activities of Daily Living (ADL)/Lawton Instrumental Activities Of Daily Living Scale (IADL) [ Time Frame: 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.

  11. EuroQol (EQ-5D-5L): Health Related Quality of Life [ Time Frame: 6 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

  12. EuroQol (EQ-5D-5L): Health Related Quality of Life [ Time Frame: 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

  13. MoCA-Blind: Montreal Cognitive Assessment [ Time Frame: 6 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.


  14. MoCA-Blind: Montreal Cognitive Assessment [ Time Frame: 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.


  15. PTSS-14: Post-traumatic Stress-like Symptoms Scores >/= 45 [ Time Frame: 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Age > 18 years

  2. Presence of all of the following conditions for < 48 hours:

    i. PaO2/FiO2 < 150 with PEEP >/= 8 cm H2O OR, if ABG not available, SaO2/FiO2 ratio that is equivalent to a PaO2/FiO2 < 150 with PEEP >/= 8 cm H2O , and a confirmatory SaO2/FiO2 ratio that is again equivalent 1-6 hours later

ii. Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules.

iii. Respiratory failure not fully explained by cardiac failure or fluid overload; need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present.

Patients must be enrolled within 48 hours of meeting inclusion criteria.

Exclusion Criteria:

  1. Lack of informed consent
  2. Continuous neuromuscular blockade at enrollment
  3. Known pregnancy
  4. Currently receiving ECMO therapy
  5. Chronic respiratory failure defined as PaCO2 > 60 mm Hg in the outpatient setting
  6. Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing
  7. Actual body weight exceeding 1 kg per centimeter of height
  8. Severe chronic liver disease defined as a Child-Pugh score of 12-15 (Appendix A2)
  9. Bone marrow transplantation within the last 1 year
  10. Expected duration of mechanical ventilation of < 48 hours
  11. Decision to withhold life-sustaining treatment; except in those patients committed to full support except cardiopulmonary resuscitation if an actual cardiac arrest occurs
  12. Moribund patient not expected to survive 24 hours; if CPR provided, assess for moribund status greater than 6 from CPR conclusion
  13. Diffuse alveolar hemorrhage from vasculitis
  14. Burns > 70% total body surface
  15. Unwillingness to utilize the ARDS Network 6 ml/kg IBW ventilation protocol
  16. Previous hypersensitivity or anaphylactic reaction to cisatracurium
  17. Neuromuscular conditions that may potentiate neuromuscular blockade and/or impair spontaneous ventilation (Appendix A2)
  18. Neurologic conditions undergoing treatment for intracranial hypertension
  19. Enrollment in an interventional ARDS trial with direct impact on neuromuscular blockade and PEEP
  20. >120 hours of mechanical ventilation
  21. P/F < 200 mmHg at the time of randomization (if available)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02509078


Locations
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Sponsors and Collaborators
Massachusetts General Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: David A. Schoenfeld, PhD Massachusetts General Hospital
  Study Documents (Full-Text)

Documents provided by Boyd Taylor Thompson, Massachusetts General Hospital:
Study Protocol  [PDF] October 12, 2017
Statistical Analysis Plan  [PDF] April 12, 2018

More Information
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Additional Information:
Website for the PETAL Network  This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Boyd Taylor Thompson, Prinicipal Investigator PETAL CCC, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02509078    
Other Study ID Numbers: PETAL01ROSE
1U01HL123009-01 ( U.S. NIH Grant/Contract )
First Posted: July 27, 2015    Key Record Dates
Results First Posted: August 13, 2019
Last Update Posted: August 13, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be collected electronically and stored at the Clinical Coordinating Center at MGH. A de-identified database of all data will be available for use 3 years after the primary publication. Data can be accessed at that point via the NHLBI BioLINCC data repository.
Keywords provided by Boyd Taylor Thompson, Massachusetts General Hospital:
ARDS
neuromuscular blocker
cisatracurium
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
 Infant, Newborn, Diseases
Lung Injury
Cisatracurium
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs