Trial of Therapeutic Hypothermia in Patients With ARDS

Launched by UNIVERSITY OF MARYLAND, BALTIMORE · Sep 3, 2020

Keywords

ClinConnect Summary

The CHILL trial is a research study looking at a potential new treatment for patients with Acute Respiratory Distress Syndrome (ARDS), a serious lung condition that can occur after various illnesses or surgeries. This trial is testing whether a method called therapeutic hypothermia (cooling the body to a lower temperature) combined with medication that relaxes muscles can help improve lung function and outcomes for these patients. Researchers will compare this approach to standard care to see if it leads to more days off the ventilator (a machine that helps people breathe) within 28 days of treatment.

To be eligible for this trial, participants must be adults who are currently on a ventilator for ARDS and have specific lung measurements that indicate they are experiencing moderate to severe symptoms. They should also be enrolled in an Intensive Care Unit (ICU) and have a legal representative available to provide consent for participation. The trial aims to enroll about 340 patients over the next few years, and individuals with ARDS linked to COVID-19 can also take part. If enrolled, participants can expect to receive close monitoring and care, as well as regular assessments to gather important health data throughout the study.

Gender

ALL

Eligibility 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.