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Trial of Therapeutic Hypothermia in Patients With ARDS

ConditionRespiratory Distress Syndrome, Adult
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-85
SponsorUniversity of Maryland, Baltimore

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

SpO2 values are 80-96%

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

Treatment groups

340 Participants
are divided into 2 treatment groups
Group A: Hypothermia + Neuromuscular blockadeExperimental treatment 2 interventions
Group B: Usual Temperature ManagementActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

28-day ventilator-free days (VFDs)

Total number of days alive and not on a ventilator in the first 28 days after enrollment

Time frame
Calculated at study day 28 or death (whichever occurs first)

Secondary outcomes

1

28-day ICU-free days

Total number of days alive and not admitted to the ICU in the first 28 days after

Time frame
Calculated at study day 28 or death (whichever occurs first)
2

Survival

28-day, 60-day, and 90-day mortality

Time frame
calculated at 28, 60, and 90 days
3

non neurologic Sequential Organ Failure (SOFA) scores

SOFA score excluding neurologic component - based on PaO2/FiO2 (0-4), BP and pressor requirement (0-4), bilirubin level (0-4), platelet count (0-4), and creatinine (0-14) with total composite score 0-20

Time frame
At enrollment and study days 1, 2, 3, 4, 7, and 28
4

Oxygen saturation (SpO2)

Pulse ox reading

Time frame
Measured at enrollment, every 2 hours on enrollment day, then once on day 2, 3, 4, 7 and 28

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Maryland, Baltimore

Lead sponsor

US Department of Veterans Affairs Cooperative Studies Program

Collaborator

KAI Research

Collaborator

United States Department of Defense

Collaborator

Source ClinicalTrials.gov
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