Trial of Therapeutic Hypothermia in Patients With ARDS

Conditions

• Respiratory Distress Syndrome, Adult

Eligibility Criteria

Sex

ALL

Age

18 Years - 85 Years

Healthy Volunteers

Not accepted

Interventions

• Hypothermia — DEVICE
  Subjects will be cooled using either cooling blankets or gel-pad systems to maintain core temperature 34-35°C.
• Neuromuscular Blocking Agents — DRUG
  Subjects in the TH + NMB arm will be deeply sedated using agents at the discretion of the primary ICU team, then start continuous iv infusion of either cisatracurium, atracurium, or vecuronium titrated to 2 twitches on train of four monitoring and further titrated to ablate visible shivering.
• Standard of care — DEVICE
  Subjects who are hypothermic (≤36°C) during CRRT will receive surface warming to restore core temperature to 37°C. Patients with core temperature \>38°C will receive 650 mg acetaminophen and, if temperature remains \>38°C, surface cooling will be initiated to return core temperature to 37-38°C.

Study Details

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 Dates

Start date

Jun 29, 2021

Status verified

May 2025

Primary completion

Aug 31, 2026

Completion

Oct 31, 2026

Study Design

Enrollment

340 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Hypothermia + Neuromuscular blockade
  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.
• Active Comparator: Usual Temperature Management
  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.

Primary Outcome Measure

28-day ventilator-free days (VFDs) [ Time Frame: Calculated at study day 28 or death (whichever occurs first) ]

Central Contacts

• Carl B Shanholtz, MD
  410-328-8141
  [email protected]
• Michael L Terrin, MD/MPH
  410-706-6139
  [email protected]

Locations (19)

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