RECRUITING

Trial of Therapeutic Hypothermia in Patients With ARDS

Conditions

Respiratory Distress Syndrome, Adult ards targeted temperature management

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-06-29

Study Completion:2026-09-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04545424

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 85 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	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.

Inclusion Criteria

Exclusion 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.

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.

Contacts and Locations

Study Contact

Carl B Shanholtz, MD

CONTACT

410-328-8141

cshanhol@som.umaryland.edu

Michael L Terrin, MD/MPH

CONTACT

410-706-6139

mterrin@som.umaryland.edu

Principal Investigator

Jeffrey D Hasday, MD

PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Study Locations (Sites)

Yale University

New Haven, Connecticut, 06520

United States

Emory University

Atlanta, Georgia, 30322

United States

Rush University Medical Center

Chicago, Illinois, 60612

United States

Loyola University Chicago

Chicago, Illinois, 60660

United States

University of Maryland Medical Center

Baltimore, Maryland, 21201

United States

Johns Hopkins Hospital

Baltimore, Maryland, 21205

United States

Cooper Health System

Camden, New Jersey, 08103

United States

Cleveland Clinc

Cleveland, Ohio, 44195

United States

Oregon Health & Science University

Portland, Oregon, 97239

United States

University of Pennsylavia

Philadelphia, Pennsylvania, 19104

United States

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107

United States

Temple University

Philadelphia, Pennsylvania, 19140

United States

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234

United States

Intermountain Healthcare (Utah)

Salt Lake City, Utah, 84132

United States

University of Wisconsin

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: University of Maryland, Baltimore

Jeffrey D Hasday, MD, PRINCIPAL_INVESTIGATOR, University of Maryland, Baltimore

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-06-29

Study Completion Date2026-09-30

Study Record Updates

Study Start Date2021-06-29

Study Completion Date2026-09-30

Terms related to this study

Keywords Provided by Researchers

ards
targeted temperature management

Additional Relevant MeSH Terms

Respiratory Distress Syndrome, Adult