Trial of Therapeutic Hypothermia in Patients With ARDS (CHILL)
Respiratory Distress Syndrome, Adult
About this trial
This is an interventional treatment trial for Respiratory Distress Syndrome, Adult focused on measuring ards, targeted temperature management
Eligibility Criteria
Inclusion Criteria:
- 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 and FiO2≥0.6; 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.
Exclusion Criteria:
- 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 oxygen with well-fitting nasal cannula with flow ≥ 65 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 >0.2 mcg/kg/min of norepinephrine or equivalent dose of other pressors for >6 continuous hours prior to randomization)
- Core temperature <35.5°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
- 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
- Not likely to remain intubated for ≥48h
- Physician of record unwilling to participate
Severe underlying lung disease
- Needs ≥ 2 LPM home O2
- 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
- Burns over >20% of the body surface
- Severe chronic liver disease (Child-Pugh score 12-15)
- Previously randomized in CHILL study
- Simultaneous enrollment in another interventional trial
Sites / Locations
- Emory University
- Rush University Medical Center
- University of Illinois at ChicagoRecruiting
- Loyola University ChicagoRecruiting
- University of Maryland Medical CenterRecruiting
- Johns Hopkins HospitalRecruiting
- Cooper Health System
- Cleveland ClincRecruiting
- University of PennsylaviaRecruiting
- Thomas Jefferson UniversityRecruiting
- Temple UniversityRecruiting
- Brooke Army Medical CenterRecruiting
- Intermountain Healthcare (Utah)Recruiting
- University of WisconsinRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Hypothermia + Neuromuscular blockade
Usual Temperature Management
Deep sedation and Neuromuscular blockade (NMB) and surface temperature management to maintain core temperature between 34 and 35°C for 48h, then rewarm to 36°C at 0.33°C per h and NMB discontinued when core temp reaches 35.5°C.
Acetaminophen and surface temperature management to maintain core temperature between 37°C and 38°C. Rewarming to 37°C for hypothermia ≤36°C with continuous renal replacement therapy.