Reevaluation Of Systemic Early Neuromuscular Blockade (ROSE)

Mass General Brigham

Status and phase: Completed; Phase 3

Conditions: Acute Respiratory Distress Syndrome

Treatments: Drug: Cisatracurium Besylate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02509078

1U01HL123009-01 (U.S. NIH Grant/Contract)

PETAL01ROSE

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,008 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,008 participants in 2 patient groups

Early Neuromuscular Blockade (NMB)

Active Comparator group

Description:

Patients will receive cisatracurium besylate for the first 48 hours of the trial.

Treatment:

Drug: Cisatracurium Besylate

Control: No Routine Early NMB

No Intervention group

Description:

Use of non-study NMB will be discouraged.