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Using therapeutic hypothermia to treat patients with ARDS

Cooling to Help Injured Lungs (CHILL) Phase IIB Randomized Control Trial of Therapeutic Hypothermia in Patients With ARDS

Phase 2 Interventional University of Maryland, Baltimore · NCT04545424

This study is testing if cooling the body temperature of patients with Acute Respiratory Distress Syndrome can help them breathe better and recover more quickly compared to regular care.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment340 (estimated)
Ages18 Years to 85 Years
SexAll
SponsorUniversity of Maryland, Baltimore Academic / other
Locations19 sites (Los Angeles, California and 18 other locations)
Trial IDNCT04545424 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of therapeutic hypothermia combined with neuromuscular blocking agents in patients suffering from Acute Respiratory Distress Syndrome (ARDS). The study aims to determine if lowering the body temperature to 34-35°C for 48 hours can improve outcomes compared to standard temperature management. It will enroll approximately 340 patients across 14 clinical centers over a period of 3.5 years. The primary outcome measure is the number of ventilator-free days at 28 days post-treatment, with secondary outcomes including safety and overall mortality rates.

Who should consider this trial

Good fit: Ideal candidates are adults who are mechanically ventilated for less than 7 days and have radiologic evidence of ARDS.

Not a fit: Patients with ARDS not caused by identifiable risk factors or those who have been ventilated for more than 7 days may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates and recovery times for patients with ARDS.

How similar studies have performed: Previous studies have suggested potential benefits of therapeutic hypothermia in similar conditions, but this specific combination approach is novel.

Eligibility criteria

Show full inclusion / exclusion 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 72h of enrollment and randomization, not be fully explained by hydrostatic pulmonary edema, and must have occurred within 7 days of exposure to an ARDS-risk factor (including continuous exposure to persistent processes (e.g. sepsis, pneumonia, COVID-19).

   * 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 72h of randomization). Patients on high flow nasal oxygen or non-invasive pressure ventilation may be consented if they meet criteria for starting the 72h ARDS window but may not be enrolled and randomized until they are intubated.

Exclusion Criteria:

1. Missed moderate-severe ARDS window (\>72hrs) - Window starts when patient is intubated with a qualifying P/F ratio of ≤ 200 with PEEP ≥ 8 cm H2O or on high flow nasal oxygen with well-fitting nasal cannula with flow ≥ 40 LPM and FiO2 ≥ 0.65 or on non-invasive pressure ventilation with PEEP ≥ 8 cm H2O and FiO2 ≥ 0.6.
2. Missed NMB window: (\>48 hrs)
3. Missed mechanical ventilation window (\>7 days)
4. Refractory hypotension (continuous infusion of \>0.3 mcg/kg/min of norepinephrine or equivalent dose of other vasopressors within 2 hours prior to randomization)
5. Core temperature \<35°C for ≥6 hours while not receiving CRRT on day of randomization
6. Significant, active bleeding (\>3u blood products and/or surgical/IR intervention) on day of randomization
7. Platelets \<10K/mm3 (uncorrected) on day of randomization
8. Active hematologic malignancy and not expected to survive 6 months
9. Skin process that 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 at time of randomization (excluding patients receiving full support EXCEPT CPR for cardiac arrest)
13. Not likely to remain intubated for ≥48h
14. Physician of record unwilling to participate
15. Severe underlying lung disease

    1. Needs \> 2 LPM or \>28% continuous home O2 (adjusted for altitude)
    2. On BIPAP (except for OSA)
    3. Prior lung transplantation
16. Pregnant at time of randomization
17. BMI consistently \>50 kg/m2
18. Known NYHA class IV heart disease
19. Acute Coronary Syndrome (MI, unstable angina) within 30 days of randomization
20. Cardiac arrest within 30 days of randomization with sequelae likely to increase mortality and/or time to ventilator liberation.
21. Burns over \>20% of the body surface
22. Severe chronic liver disease (Child-Pugh score 12-15)
23. Previously randomized in CHILL study
24. Simultaneous enrollment in another inpatient interventional trial started during the current hospitalization.
25. On ECMO during the current hospitalization.

Where this trial is running

Los Angeles, California and 18 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Respiratory Distress Syndrome, Adultardstargeted temperature management
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.