Working Toward the Advancement of Recovery Using Modulated Therapeutic Hyperthermia (WARMTH) in Sepsis - Pilot (WARMTH)

The purpose of this pilot study is to demonstrate the ability to warm critically ill patients with sepsis to a target temperature of 39°C

Study Overview

• Status: Withdrawn
• Conditions: Sepsis
• Intervention / Treatment: Other: Multimodal therapeutic warming w/ esophageal d/c; Other: Multimodal therapeutic warming w/ conductive d/c

Detailed Description

Participants with sepsis and without fever will be warmed with surface (forced air and conductive wraps) and core (esophageal) warming, and will have the warming devices placed in the ICU. The warming devices will remain in place until the study is completed (36 hours). The heat exchangers will be set to attain a patient target temperature of 39°C as rapidly as possible, after which the forced-air (non-servo) system will be removed, and the conductive system heat exchanger (powering the water blankets and esophageal device, both of which are servo-controlled) will be set to maintain patient temperature at 39°C for the duration of the study period.

Once goal temperature has been achieved for 2 consecutive hours, the forced air warming device will be discontinued. Patients will be randomized at this point to Group 1, in which esophageal warming will be discontinued first or to Group 2, in which external conductive warming will be discontinued first.

All patients will have usual standard of care labs, vital signs, and imaging for patients undergoing mechanical ventilation in the ICU. For the duration of the 36-hour intervention, patient vital signs, including blood pressure, heart rate, respiratory rate, and vasopressor requirements will be monitored and recorded every 6 hours. Core temperature will be measured and recorded hourly.

Patient's clinical status and outcome will be reviewed in the medical chart 7 days after study completion.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients above the age of 18 years old.
• Patients with sepsis diagnosed within 48 hours of enrollment. For the purpose of this protocol, sepsis onset is defined as administration of intravenous antibiotics in a patient that the treating critical care physician feels is ill from sepsis.
• All qualifying patients must have a sequential organ failure assessment (SOFA) score of 2 or greater at the time of enrollment.
• Patients requiring mechanical ventilation with an expected duration of mechanical ventilation of >= 2 days.
• Patient maximum baseline documented temperature (within previous 24 hours) < 38.3°C.

Exclusion Criteria:

• Patients without legally authorized representative able to provide informed consent.
• Patients with contraindication to core warming using an esophageal core warming device, surface warming using conductive heat transfer, and forced air warmer.
• Patients known to be pregnant.
• Patients with <40 kg of body mass.
• Patients with comfort care only status.
• Patients with contraindications to hyperthermia treatment (acute stroke, acute traumatic brain injury, acute spinal cord injury, post-cardiac arrest, multiple sclerosis, or sickle cell disease).
• Expected continuous dialysis within 48 hours after enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conductive Wrap Warming; Esophageal warming will be discontinued first	Other: Multimodal therapeutic warming w/ esophageal d/c; In order to evaluate the ability to reliably raise patient temperature to a target of 39.0°C, patients will be warmed with forced air warming, surface conductive warming, and esophageal core warming. After 4 hours at target temperature, esophageal warming will be discontinued.
Experimental: Esophageal Warming; Conductive wraps will be discontinued first	Other: Multimodal therapeutic warming w/ conductive d/c; In order to evaluate the ability to reliably raise patient temperature to a target of 39.0°C, patients will be warmed with forced air warming, surface conductive warming, and esophageal core warming. After 4 hours at target temperature, conductive warming will be discontinued.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of warming critically ill patients with sepsis using a multimodal sepsis warming protocol.	Our primary outcome is the proportion of patients who achieve goal temperature within 6 hours of starting warming. After discontinuing devices, we will monitor the proportion of participants who remain at the goal temperature. Warming will be performed using standard technique per instructions for use for the surface warming wraps, esophageal heat transfer device, and forced air warming device. The heat exchanger will be set to a target patient temperature of 39°C, with patient temperature measured via temperature sensing Foley catheter or rectal temperature sensor. Feedback (servo) control is provided by the heat exchanger (Blanketrol III, Gentherm Medical, Cincinnati, OH), such that the water temperature flow through the warming devices is adjusted automatically to enable attainment of the target temperature. Forced air warming will be used until goal temperature is reached for at least 2 hours, then other devices will be used to maintain temperature.	36 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the rate of temperature change of patients undergoing a sepsis warming protocol.	Participants will be initiated on a warming protocol with forced air warming, surface conductive, and esophageal core warming with the target temperature of 39°C. Patient temperature measurement will be collected hourly during the study period (36 hours).	36 hours
Determine the ability of conductive heat wraps vs. conductive esophageal device to maintain therapeutic hyperthermia	Once goal temperature has been achieved for 2 consecutive hours, the forced air warming device will be discontinued. Participants will be randomized at this point to Group 1, in which esophageal warming will be discontinued first or to Group 2, in which external conductive warming will be discontinued first. Once goal temperature has been achieved for 4 consecutive hours after discontinuation of the forced air warming device, the second device will be discontinued. If patient body temperature drops below goal temperature, the second warming device will be restarted to maintain temperature.	36 hours

Collaborators and Investigators

• Sponsor: Nicholas M Mohr
• Collaborators: Washington University School of Medicine; Hennepin County Medical Center, Minneapolis
• Investigators: Principal Investigator: Nicholas Mohr, MD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2021
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: June 25, 2021
• First Submitted That Met QC Criteria: July 2, 2021
• First Posted (Actual): July 14, 2021

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 8, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: fever; sepsis; hyperthermia
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Sepsis; Toxemia; Hyperthermia; Fever
• Other Study ID Numbers: H202104263

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No