Trial of Therapeutic Hypothermia in Patients With ARDS

• Status: Recruiting
• Trial end date: 2024-06-30
• 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 CHILL trial is designed to evaluate whether TH combined with NMBA is beneficial in patients with ARDS. This Phase IIb randomized clinical trial is funded by the Department of Defense to compare TH (core temperature 34-35°C) + NMBA for 48h vs. usual temperature management in patients in 14 clinical centers with the Clinical Coordination Center and Data Coordinating Center at University of Maryland Baltimore. Planned enrollment is 340 over ~3.5 years of the 4-year contract. Since COVID-19 is currently the most common cause of ARDS, randomization will be stratified on COVID-19 status and patients with COVID-19 limited to no more than one-third of budgeted enrollment per year. Primary outcome is 28-day ventilator-free days. Secondary outcomes include safety, physiologic measures, mortality, hospital and ICU length of stay, and serum biomarkers collected at baseline and on days 1, 2, 3, 4, and 7.

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

Details

• Lead Sponsor: University of Maryland, Baltimore
• Collaborators: KAI Research; United States Department of Defense; US Department of Veterans Affairs Cooperative Studies Program
• Treatments: Neuromuscular Blocking Agents

Criteria

Inclusion Criteria:

1. endotracheal tube or tracheostomy in place and mechanically ventilated for ≤7 days;

2. admitted to a participating ICU

3. radiologic evidence of bilateral pulmonary infiltrates not fully explained by pleural effusions, atelectasis, or hydrostatic pulmonary edema

4. P/F ratio <200 with PEEP ≥8 cm H2O; If ABG values are not available, the P/F ratio may be inferred from SpO2 values based on Table 3 from Brown et al as long as following conditions are met:

1. SpO2 values are 80-96%

2. SpO2 is measured ≥10 min after any change in FIO2

3. PEEP is ≥ 8 cm H2O

4. the pulse oximeter waveform tracing is adequate

5. the qualifying inferred P/F ratio is confirmed 1-6h after initial determination.

5. access to an LAR to provide consent.

6. Criteria 3 AND 4 must be met within 48h of enrollment and randomization, not be fully explained by hydrostatic pulmonary edema, and must have occurred within 7 days onset of a condition associated with ARDS.

• Patients may be enrolled and decision about randomization delayed if all criteria other than P/F ratio < 200 are met and then randomized if and when the P/F ratio < 200 (as long as this occurs within 48h of randomization).

Exclusion Criteria:

1. Missed ARDS window (>48hrs)

2. Missed NMB window: (>12 hrs)

3. Missed mechanical ventilation window (>7 days)

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

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

6. Patient is unable to give consent and no Legally authorized representative is available

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

8. Platelets <10K/mm3 (uncorrected)

9. Active hematologic malignancy

10. Skin process that precludes cooling device

11. Moribund, not likely to survive 72h

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

13. Do Not Resuscitate status

14. Not likely to remain intubated for ≥48h

15. Physician of record unwilling to participate

16. Severe underlying lung disease

1. On home O2

2. On BIPAP (except for OSA)

3. Prior lung transplantation

17. Pregnant

18. BMI >50 kg/m2

19. Known NYHA class IV heart disease

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

21. Cardiac arrest within 30 days of enrollment

22. Burns over >20% of the body surface

23. Severe chronic liver disease (Child-Pugh score 12-15)

24. Previously randomized in CHILL study