Trial of Therapeutic Hypothermia in Patients With ARDS

Recruiting now · Phase 2

Conditions studied: Respiratory Distress Syndrome, Adult

In brief

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. COVID-19 is considered an ARDS risk-factor and patients with ARDS secondary to COVID-19 pneumonia will be eligible for enrollment. 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.

Key facts

Study ID: NCT04545424
Run by: University of Maryland, Baltimore
People needed: 340
Starts: 2021-06-29
Expected to finish: 2026-10-31
Last updated by the study team: 2025-11-10

Who can join

Age: 18 and older, up to 85. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

endotracheal tube or tracheostomy in place and mechanically ventilated for ≤7 days;
admitted to a participating ICU
radiologic evidence of bilateral pulmonary infiltrates not fully explained by pleural effusions, atelectasis, or hydrostatic pulmonary edema
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:
SpO2 values are 80-96%
SpO2 is measured ≥10 min after any change in FIO2
PEEP is ≥ 8 cm H2O
the pulse oximeter waveform tracing is adequate
the qualifying inferred P/F ratio is confirmed 1-6h after initial determination.
access to an LAR to provide consent.
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.

You may not qualify if…

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.
Missed NMB window: (>48 hrs)
Missed mechanical ventilation window (>7 days)
Refractory hypotension (continuous infusion of >0.3 mcg/kg/min of norepinephrine or equivalent dose of other vasopressors within 2 hours prior to randomization)
Core temperature <35°C for ≥6 hours while not receiving CRRT on day of randomization
Significant, active bleeding (>3u blood products and/or surgical/IR intervention) on day of randomization
Platelets <10K/mm3 (uncorrected) on day of randomization
Active hematologic malignancy and not expected to survive 6 months
Skin process that precludes cooling device
Moribund, not likely to survive 72h
Pre-morbid condition makes it unlikely that patient will survive 28 days
Do Not Resuscitate status at time of randomization (excluding patients receiving full support EXCEPT CPR for cardiac arrest)
Not likely to remain intubated for ≥48h
Physician of record unwilling to participate
Severe underlying lung disease
Needs > 2 LPM or >28% continuous home O2 (adjusted for altitude)
On BIPAP (except for OSA)
Prior lung transplantation
Pregnant at time of randomization
BMI consistently >50 kg/m2
Known NYHA class IV heart disease
Acute Coronary Syndrome (MI, unstable angina) within 30 days of randomization
Cardiac arrest within 30 days of randomization with sequelae likely to increase mortality and/or time to ventilator liberation.
Burns over >20% of the body surface
Severe chronic liver disease (Child-Pugh score 12-15)

Where it is running

Oregon Health & Science University — Portland, Oregon, United States (enrolling)
University of Pennsylavia — Philadelphia, Pennsylvania, United States (enrolling)
Thomas Jefferson University — Philadelphia, Pennsylvania, United States (enrolling)
Temple University — Philadelphia, Pennsylvania, United States (enrolling)
Rush University Medical Center — Chicago, Illinois, United States (enrolling)
Intermountain Healthcare (Utah) — Salt Lake City, Utah, United States (enrolling)
University of Maryland Medical Center — Baltimore, Maryland, United States (enrolling)
Emory University — Atlanta, Georgia, United States (enrolling)
Henry Ford Hospital — Detroit, Michigan, United States (enrolling)
Cooper Health System — Camden, New Jersey, United States (enrolling)
University of Cincinnati — Cincinnati, Ohio, United States (enrolling)
Cleveland Clinc — Cleveland, Ohio, United States (enrolling)
University of Wisconsin — Madison, Wisconsin, United States
Yale University — New Haven, Connecticut, United States
Loyola University Chicago — Chicago, Illinois, United States
University of Kentucky — Lexington, Kentucky, United States
Johns Hopkins Hospital — Baltimore, Maryland, United States
Brooke Army Medical Center — Fort Sam Houston, Texas, United States
Cedars-Sinai Medical Center — Los Angeles, California, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.