Reevaluation Of Systemic Early Neuromuscular Blockade

NCT ID: NCT02509078

Last Updated: 2019-08-13

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1008 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-04

Study Completion Date

2019-04-04

Brief Summary

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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

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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.

Conditions

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Acute Respiratory Distress Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Early Neuromuscular Blockade (NMB)

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

Group Type ACTIVE_COMPARATOR

Cisatracurium Besylate

Intervention Type DRUG

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.

Control: No Routine Early NMB

Use of non-study NMB will be discouraged.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Nimbex

Eligibility Criteria

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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.

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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Boyd Taylor Thompson

Prinicipal Investigator PETAL CCC

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David A. Schoenfeld, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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UCSF Fresno

Fresno, California, United States

Site Status

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Site Status

UC Davis Medical Center

Sacramento, California, United States

Site Status

UCSF Medical Center

San Francisco, California, United States

Site Status

Stanford University Hospital

Stanford, California, United States

Site Status

Medical Center of Aurora

Aurora, Colorado, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Denver Health Medical Center

Denver, Colorado, United States

Site Status

Swedish Medical Center

Englewood, Colorado, United States

Site Status

Indiana University Methodist Hospital

Indianapolis, Indiana, United States

Site Status

University Medical Center

New Orleans, Louisiana, United States

Site Status

Maine Medical Center

Portland, Maine, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Baystate Medical Center

Springfield, Massachusetts, United States

Site Status

St. Vincent's Hospital

Worcester, Massachusetts, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Henry Ford Medical Center

Detroit, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Mt. Sinai Hospital

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Wesley Long Hospital

Greensboro, North Carolina, United States

Site Status

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Summa Akron City Hospital

Akron, Ohio, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

UPMC Presbyterian/Mercy/Shadyside

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

McKay-Dee Hospital

Ogden, Utah, United States

Site Status

Utah Valley Regional Medical Center

Provo, Utah, United States

Site Status

University Hospital

Salt Lake City, Utah, United States

Site Status

LDS Hospital

Salt Lake City, Utah, United States

Site Status

University or Virginia Health System

Charlottesville, Virginia, United States

Site Status

VCU Medical Center

Richmond, Virginia, United States

Site Status

Harborview Medical Center

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Swedish Hospital Cherry Hill

Seattle, Washington, United States

Site Status

Swedish Hospital First Hill

Seattle, Washington, United States

Site Status

Countries

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United States

References

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National Heart, Lung, and Blood Institute PETAL Clinical Trials Network; Moss M, Huang DT, Brower RG, Ferguson ND, Ginde AA, Gong MN, Grissom CK, Gundel S, Hayden D, Hite RD, Hou PC, Hough CL, Iwashyna TJ, Khan A, Liu KD, Talmor D, Thompson BT, Ulysse CA, Yealy DM, Angus DC. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med. 2019 May 23;380(21):1997-2008. doi: 10.1056/NEJMoa1901686. Epub 2019 May 19.

Reference Type DERIVED
PMID: 31112383 (View on PubMed)

Sjoding MW, Schoenfeld DA, Brown SM, Hough CL, Yealy DM, Moss M, Angus DC, Iwashyna TJ; NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. Power Calculations to Select Instruments for Clinical Trial Secondary Endpoints. A Case Study of Instrument Selection for Post-Traumatic Stress Symptoms in Subjects with Acute Respiratory Distress Syndrome. Ann Am Thorac Soc. 2017 Jan;14(1):110-117. doi: 10.1513/AnnalsATS.201608-585OC.

Reference Type DERIVED
PMID: 27788018 (View on PubMed)

Huang DT, Angus DC, Moss M, Thompson BT, Ferguson ND, Ginde A, Gong MN, Gundel S, Hayden DL, Hite RD, Hou PC, Hough CL, Iwashyna TJ, Liu KD, Talmor DS, Yealy DM; Reevaluation of Systemic Early Neuromuscular Blockade Protocol Committee and the National Institutes of Health National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network Investigators. Design and Rationale of the Reevaluation of Systemic Early Neuromuscular Blockade Trial for Acute Respiratory Distress Syndrome. Ann Am Thorac Soc. 2017 Jan;14(1):124-133. doi: 10.1513/AnnalsATS.201608-629OT.

Reference Type DERIVED
PMID: 27779896 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://petalnet.org

Website for the PETAL Network

Other Identifiers

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1U01HL123009-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PETAL01ROSE

Identifier Type: -

Identifier Source: org_study_id

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