Pilot RCT of Therapeutic Hypothermia Plus Neuromuscular Blockade in COVID-19 Patients With ARDS (CHILL-pilot)
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|ClinicalTrials.gov Identifier: NCT03376854|
Recruitment Status : Recruiting
First Posted : December 19, 2017
Last Update Posted : June 16, 2020
|Condition or disease||Intervention/treatment||Phase|
|Respiratory Distress Syndrome, Adult Sars-CoV2||Device: Hypothermia Drug: Neuromuscular Blocking Agents Device: Standard of Care||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Randomized (1:1) control (non-blinded) trial|
|Masking:||None (Open Label)|
|Masking Description:||Since it will be obvious to observers of the subjects whether they are in the treatment (TH+NMB) or control groups, the study is not masked but all treatments that determine outcome are protocolized.|
|Official Title:||Pilot Randomized Clinical Trial of Therapeutic Hypothermia Plus Neuromuscular Blockade vs. Standard of Care in COVID-19 Patients With Moderate to Severe ARDS - the Cooling to Help Injured Lungs (CHILL) Pilot Study|
|Actual Study Start Date :||May 1, 2018|
|Estimated Primary Completion Date :||November 30, 2020|
|Estimated Study Completion Date :||December 31, 2020|
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.
Subjects will be cooled using either cooling blankets or gel-pad systems to maintain core temperature 34-35°C.
Other Name: Targeted temperature Management
Drug: Neuromuscular Blocking Agents
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.
Other Name: Paralytics
Active Comparator: Standard of care
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.
Device: Standard of Care
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.
Other Name: Usual temperature management
- Targeted temperature compliance [ Time Frame: Randomization through day 3 ]The total time in hours from beginning of cooling to beginning of rewarming during which the patient's core temperature was within the target range of 34-35°C.
- Adverse event [ Time Frame: Randomization through study day 3 ]Adverse events expected during cooling, including hemorrhage, bradycardia, and hypotension.
- 28-day ICU-free days [ Time Frame: Calculated at study day 28 or death (whichever occurs first) ]Total number of days alive and not admitted to the ICU in the first 28 days after
- Survival [ Time Frame: calculated at 28, 60, and 90 days ]28-day, 60-day, and 90-day mortality
- non neurologic Sequential Organ Failure (SOFA) scores [ Time Frame: At enrollment and study days 1, 2, 3, 4, 7, and 28 ]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
- Oxygen saturation (SpO2) [ Time Frame: Measured at enrollment, every 4 hours on enrollment day, then once on day 2, 3, 4, 7 and 28 ]Pulse ox reading
- Plateau airway pressure [ Time Frame: Measured at enrollment, every 4 hours on enrollment day, then once on day 2, 3, 4, and 7 or until extubation whichever occurs first ]On machine initiated breath
- Mean airway pressure [ Time Frame: Measured at enrollment, every 4 hours on enrollment day, then once on day 2, 3, 4, and 7 or until extubation whichever occurs first ]Direct ventilator measurement on machine initiated breath
- Airway driving pressure [ Time Frame: Measured at enrollment, every 4 hours on enrollment day, then once on day 2, 3, 4, and 7 or until extubation whichever occurs first ]Plateau pressure - PEEP (machine initiated breath)
- Oxygen saturation index [ Time Frame: Measured at enrollment, every 4 hours on enrollment day, then once on day 2, 3, 4, and 7 or until extubation whichever occurs first ]Mean airway pressure x 100 x FiO2/SpO2
- Core temperature [ Time Frame: Measured continuously and recorded at enrollment, every 2 hours on the day of enrollment, and mornings on study day 2, 3, 4, and 7 ]Measured continuously from iv catheter, urinary catheter, or esophageal probe.
- Urine output [ Time Frame: Daily on study day 1, 2, 3, 4, and 7 ]24 hour urine volume
- comprehensive metabolic panel [ Time Frame: Daily on study day 1, 2, 3, 4, and 7 ]performed in clinical lab
- Complete blood count with differential count and platelet count [ Time Frame: Daily on study day 1, 2, 3, 4, and 7 ]preformed in clinical lab
- Biomarkers [ Time Frame: Daily on study day 1, 2, 3, 4, and 7 ]10 ml blood draw
- Serum electrolytes [ Time Frame: Every 8 hours until study hour 60 ]performed in clinical lab
- Blood glucose [ Time Frame: Every 4 hours until study hour 60 ]Beside blood glucose testing
- 28-day ventilator-free days [ Time Frame: Calculated at study day 28 or death (whichever occurs first) ]Total number of days alive and not on a ventilator in the first 28 days after enrollment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03376854
|Contact: Jeffrey D Hasday, MDemail@example.com|
|Contact: Carl B Shanholtz, MDfirstname.lastname@example.org|
|Principal Investigator:||Jeffrey D Hasday, MD||University of Maryland, Baltimore|