Pilot RCT of Therapeutic Hypothermia Plus Neuromuscular Blockade in COVID-19 Patients With ARDS

• Status: Withdrawn
• Trial end date: 2021-04-27
• Target enrollment: 0
• Participant gender: All

Summary

Acute Respiratory Distress Syndrome (ARDS) is a serious condition that occurs as a complication of medical and surgical diseases, has a mortality of ~40%, and has no known treatment other than optimization of support. Data from basic research, animal models, and retrospective studies, case series, and small prospective studies suggest that therapeutic hypothermia (TH) similar to that used for cardiac arrest may be lung protective in patients with ARDS; however, shivering is a major complication of TH, often requiring paralysis with neuromuscular blocking agents (NMBA) to control. Since the recently completed NHLBI PETAL ROSE trial showed that NMBA had no effect (good or bad) in patients with moderate to severe ARDS, the investigators sought to evaluate whether TH combined with NMBA is beneficial in patients with ARDS. The investigators are scheduled to begin enrolling in a Department of Defense-funded Phase IIb multicenter RCT of TH (core temperature 34-35°C) + NMBA for 48h vs. usual temperature management in patients with ARDS with time on ventilator as the primary outcome. Since COVID-19 is now the most common cause of ARDS, we are conducting a pilot study to examine the safety and feasibility of including patients with COVID-19-associated ARDS in our upcoming trial. In this pilot, we will randomize 20 patients with COVID-19 and ARDS to either TH+NMBA for 48h or usual temperature management. The primary outcome is achieving and maintaining the target temperature. Secondary outcomes include safety, physiologic measures, mortality, hospital and ICU length of stay, and serum biomarkers collected on days 0, 1, 2, 3, 4, and 7.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Maryland; University of Maryland, Baltimore
• Treatments: Neuromuscular Blocking Agents

Criteria

Inclusion Criteria for Enrollment

1. COVID-19 diagnosed by PCR within 3 weeks

2. men and women

3. any race/ethnicity

4. 18-65 years of age

5. endotracheal tube or tracheostomy in place and mechanically ventilated for < 7 days;

6. radiologic evidence of bilateral pulmonary infiltrates not fully explained by hydrostatic pulmonary edema

7. access to an LAR to provide consent (remote consent is permissible).

Additional inclusion criteria required for randomization:

1. meet all inclusion/exclusion criteria for enrollment

2. have a P/F ratio <200 with PEEP ≥8 cm H2O either from ABG or imputed from SpO2 as described by Brown et al (Chest 2016; 150:307).

Exclusion Criteria:

1. Missed ARDS window (>48hrs)

2. Missed mechanical ventilation window (>7 days)

3. Refractory hypotension (> 0.2 mcg/kg/min of norepinephrine or equivalent dose for minimum of 6 h)

4. Core temperature <35.5°C while not receiving CRRT

5. Patient is unable to give consent and no legally authorized representative is available;

6. Significant, active bleeding (>3u blood products and/or surgical/IR intervention)

7. Platelets <10K/mm3 (uncorrected)

8. Active hematologic malignancy

9. Skin process precludes cooling device

10. Moribund, not likely to survive 72h

11. Pre-morbid condition makes it unlikely that patient will survive 28 days

12. Do Not Resuscitate status

13. Not likely to remain intubated for ≥48h

14. Physician unwilling to participate

15. Severe underlying lung disease

1. On home O2

2. On BIPAP (except for OSA)

3. Prior lung transplantation

16. BMI >45 kg/m2

17. Known NYHA class IV heart disease

18. Acute Coronary Syndrome past 30 days (MI, unstable angina)

19. Cardiac arrest within 30 days of enrollment

20. burns over >20% of the body surface

21. severe chronic liver disease (Child-Pugh of 12-15)

22. Previously randomized in CHILL study