Reevaluation Of Systemic Early Neuromuscular Blockade

Acute Respiratory Distress Syndrome Clinical Trial

— ROSE  

Official title:

Reevaluation Of Systemic Early Neuromuscular Blockade

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02509078
• Other study ID #: PETAL01ROSE
• Secondary ID: 1U01HL123009-01
• Status: Completed
• Phase: Phase 3
• Start date: January 4, 2016
• Est. completion date: April 4, 2019

Study information

• Verified date: July 2019
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1008
• Est. completion date: April 4, 2019
• Est. primary completion date: July 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

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.

Locations

Country	Name	City	State
United States	Summa Akron City Hospital	Akron	Ohio
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Medical Center of Aurora	Aurora	Colorado
United States	University of Colorado Hospital	Aurora	Colorado
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	University or Virginia Health System	Charlottesville	Virginia
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Denver Health Medical Center	Denver	Colorado
United States	Henry Ford Medical Center	Detroit	Michigan
United States	Swedish Medical Center	Englewood	Colorado
United States	UCSF Fresno	Fresno	California
United States	Wesley Long Hospital	Greensboro	North Carolina
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Indiana University Methodist Hospital	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	Intermountain Medical Center	Murray	Utah
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University Medical Center	New Orleans	Louisiana
United States	Mt. Sinai Hospital	New York	New York
United States	McKay-Dee Hospital	Ogden	Utah
United States	UPMC Presbyterian/Mercy/Shadyside	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Oregon Health and Science University	Portland	Oregon
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	VCU Medical Center	Richmond	Virginia
United States	UC Davis Medical Center	Sacramento	California
United States	LDS Hospital	Salt Lake City	Utah
United States	University Hospital	Salt Lake City	Utah
United States	UCSF Medical Center	San Francisco	California
United States	Harborview Medical Center	Seattle	Washington
United States	Swedish Hospital Cherry Hill	Seattle	Washington
United States	Swedish Hospital First Hill	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Stanford University Hospital	Stanford	California
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina
United States	St. Vincent's Hospital	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hospital Mortality to Day 90	The percentage of subjects alive at study day 90. Those subjects discharged home prior to day 90 were counted as alive at day 90.	90 days after randomization
Secondary	Mean Ventilator Free Days to Day 28	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.	28 days after randomization
Secondary	Mean Organ Failure Free Days to Day 28	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.	28 days after randomization
Secondary	ICU Free Days to Day 28	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).	28 days after randomization
Secondary	Mean Hospital Free Days to Days 28	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.	28 days after randomization
Secondary	Katz Activities of Daily Living (ADL)/Lawton Instrumental Activities Of Daily Living Scale (IADL)	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.	3 months after randomization
Secondary	EuroQol (EQ-5D-5L): Health Related Quality of Life	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	3 months after randomization
Secondary	PTSS-14: Post-traumatic Stress-like Symptoms Scores >/= 45	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.	6 months after randomization
Secondary	MoCA-Blind: Montreal Cognitive Assessment	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.	3 months after randomization
Secondary	Katz Activities of Daily Living (ADL)/Lawton Instrumental Activities Of Daily Living Scale (IADL)	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 months after randomization
Secondary	Katz Activities of Daily Living (ADL)/Lawton Instrumental Activities Of Daily Living Scale (IADL)	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.	12 months after randomization
Secondary	EuroQol (EQ-5D-5L): Health Related Quality of Life	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	6 months after randomization
Secondary	EuroQol (EQ-5D-5L): Health Related Quality of Life	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 months after randomization
Secondary	MoCA-Blind: Montreal Cognitive Assessment	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.	6 months after randomization
Secondary	MoCA-Blind: Montreal Cognitive Assessment	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.	12 months after randomization
Secondary	PTSS-14: Post-traumatic Stress-like Symptoms Scores >/= 45	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.	12 months after randomization

External Links

•   Website for the PETAL Network