Mild Hypothermia and Acute Kidney Injury in Liver Transplantation (MHALT)

May 15, 2025 updated by: University of California, San Francisco

Mild Hypothermia and Acute Kidney Injury in Liver Transplantation (MHALT) Trial

Acute kidney injury (AKI), or worsening kidney function, is a common complication after liver transplantation (20-90% in published studies). Patients who experience AKI after liver transplantation have higher mortality, increased graft loss, longer hospital and intensive care unit stays, and more progression to chronic kidney disease compared with those who do not. In this study, half of the participants will have their body temperature cooled to slightly lower than normal (mild hypothermia) for a portion of the liver transplant operation, while the other half will have their body temperature maintained at normal. The study will evaluate if mild hypothermia protects from AKI during liver transplantation.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This study is a randomized controlled trial of mild hypothermia during liver transplantation to provide protection from AKI. Participants will be randomized to normothermia (36.5-37.5 °C) versus mild hypothermia (34-35 °C) during a portion of the liver transplant operation. The protocol is based on preliminary data from rodent models showing that hypothermia protects the kidneys from ischemia-reperfusion injury, as well as studies in deceased organ donors showing that cooling improves post-transplant organ function. Temperature will be maintained with standard techniques plus a minimally-invasive esophageal cooling device that is approved by the U.S. Food and Drug Administration. The investigators hypothesize that mild hypothermia will reduce the incidence and severity of AKI after liver transplantation(LTx). Standard surrogates (e.g., change in serum creatinine, need for initiation of dialysis) and biomarkers will be used to assess the severity of kidney injury.

Study Type

Interventional

Enrollment (Actual)

175

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Anschutz Medical Campus
    • Texas
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Liver transplantation from a donor after neurologic determination of death

Exclusion Criteria:

  • Liver transplantation from a donor after cardiac death
  • Acute liver failure
  • Living-donor liver transplantation
  • Simultaneous liver-kidney transplantation
  • Preoperative renal replacement therapy
  • Preoperative intubation
  • Portopulmonary hypertension
  • Machine perfusion of liver graft

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Mild hypothermia & Esophageal cooling/warming device
The target core temperature is 34-35 °C.
Device: Esophageal cooling/warming device
The EnsoETM (formerly known as Esophageal Cooling Device) is a non-sterile multilumen silicone tube placed in the esophagus for the purpose of cooling or warming a patient while allowing gastric decompression and drainage. It is placed in a manner identical to a standard orogastric tube, which is standard equipment for liver transplant surgery. It is removed at the end of surgery. Control of the patient's temperature is achieved by connecting the EnsoETM to an external heat exchanger (Gaymar Medi-Therm III or similar system). The Medi-Therm III is a standard device used in operating rooms for warming patients with a conductive table warming pad. The Medi-Therm III circulates temperature-controlled water through a closed-loop system via the two outer lumens of the EnsoETM. Water temperature ranges from 4°C - 42°C.
Other Names:
  • EnsoETM
  • ECD - Esophageal Cooling Device
Other: Mild hypothermia
Cooling will be initiated after induction of anesthesia and maintained throughout the anhepatic phase of liver transplantation. In all feasible cases the surgeon will cover the peritoneal surface over the right kidney, which is exposed during the operation, with ice-cold sponges to enhance cooling of the renal parenchyma. After blood flow is completely restored to the liver, the esophageal cooling device and other standard measures (forced-air, fluid, and table warmers, plus a heated anesthesia circuit) will be used to actively re-warm the patient (expected warming rate ≥ 1 deg C/hour). The goal is to achieve normothermia by case end.
Active Comparator: Normothermia & Esophageal cooling/warming device
The target core temperature is 36.5-37.5 °C.
Device: Esophageal cooling/warming device
The EnsoETM (formerly known as Esophageal Cooling Device) is a non-sterile multilumen silicone tube placed in the esophagus for the purpose of cooling or warming a patient while allowing gastric decompression and drainage. It is placed in a manner identical to a standard orogastric tube, which is standard equipment for liver transplant surgery. It is removed at the end of surgery. Control of the patient's temperature is achieved by connecting the EnsoETM to an external heat exchanger (Gaymar Medi-Therm III or similar system). The Medi-Therm III is a standard device used in operating rooms for warming patients with a conductive table warming pad. The Medi-Therm III circulates temperature-controlled water through a closed-loop system via the two outer lumens of the EnsoETM. Water temperature ranges from 4°C - 42°C.
Other Names:
  • EnsoETM
  • ECD - Esophageal Cooling Device
Other: Normothermia
After induction of anesthesia, the esophageal cooling/warming device and standard warming measures will be used to maintain normothermia throughout the operation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Kidney Injury (AKI)
Time Frame: 72 hours from the end of surgery
Acute Kidney Injury (AKI) is defined according to the International Club for Ascites (ICA) 2015 criteria, a revision of the Kidney Disease Improving Global Outcome (KDIGO) criteria for patients with cirrhosis (Angeli P, Ginès P, Wong F, Bernardi M, Boyer TD, Gerbes A, et al. Gut. 2015 Apr;64(4):531-7). AKI is defined as an increase in sCr ≥ 0.3 mg/dL within 48 hours, or a percentage increase ≥ 50% from baseline, or the initiation of renal replacement therapy. Baseline creatinine is defined as the most recent value obtained prior to liver transplantation.
72 hours from the end of surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Distribution of the Stages of Acute Kidney Injury (AKI)
Time Frame: 72 hours from the end of surgery

The International Club for Ascites (ICA) 2015 criteria, a revision of the Kidney Disease Improving Global Outcome (KDIGO) criteria for patients with cirrhosis (Angeli P, Ginès P, Wong F, Bernardi M, Boyer TD, Gerbes A, et al. Gut. 2015 Apr;64(4):531-7), will be used to define the stage of AKI (Stage 1, 2, or 3). The distribution of the stages of AKI within 72 hours after liver transplantation. The stages of AKI are defined as follows based on the serum creatinine (sCr):

AKI Stage 1: increase in sCr ≥ 0.3 mg/dL, or an increase in sCr ≥ 1.5-fold and ≤ 2-fold from baseline.

AKI Stage 2: increase in sCr > 2-fold and ≤ 3-fold from baseline. AKI Stage 3: increase in sCr > 3-fold from baseline, or sCr ≥ 4.0 with an acute increase of ≥ 0.3 mg/dL, or initiation of renal replacement therapy.
72 hours from the end of surgery
Duration of Intensive Care Unit (ICU) Stay
Time Frame: Time from end of liver transplant to ICU discharge, approximately 1 to 3 days
Time after liver transplantation until patient is discharged from the ICU to a regular hospital bed.
Time from end of liver transplant to ICU discharge, approximately 1 to 3 days
Duration of Hospital Stay
Time Frame: Time from liver transplant to hospital discharge, approximately 1-2 weeks.
From the date of liver transplantation until the date patient is discharged from the hospital.
Time from liver transplant to hospital discharge, approximately 1-2 weeks.
Patient Survival
Time Frame: up to 1 year
From the date of liver transplantation until the date of death from any cause.
up to 1 year
Need for Renal Replacement Therapy
Time Frame: 72 hours, 30 days, and 1 year. The original protocol specified assessment at 1 week after surgery. However, this data was unable to be collected and we are only able to determine the outcome at 72 hours, 30 days, and 1 year.
Patient is receiving continuous renal replacement therapy or dialysis at the time of follow-up. If patient died before the indicated follow-up time, the outcome was counted as positive (patient was on renal replacement therapy).
72 hours, 30 days, and 1 year. The original protocol specified assessment at 1 week after surgery. However, this data was unable to be collected and we are only able to determine the outcome at 72 hours, 30 days, and 1 year.
Persistent Renal Dysfunction
Time Frame: 90 days and 1 year
Presence of a reduction in GFR by ≥ 25 mL/min or ≥ 50% from baseline at the time of follow-up. If patient died before the indicated follow-up time, the outcome was counted as positive (patient had persistent renal dysfunction).
90 days and 1 year
Serum Neutrophil Gelatinase-associated Lipocalin (NGAL)
Time Frame: Baseline (start of surgery) and 2 hours after reperfusion of the portal vein
Change in serum NGAL levels from baseline to 2 hours after reperfusion of the portal vein (final - initial).
Baseline (start of surgery) and 2 hours after reperfusion of the portal vein
Urine Neutrophil Gelatinase-associated Lipocalin (NGAL)
Time Frame: Baseline (start of surgery) and 2 hours after reperfusion of the portal vein
Change in urine NGAL levels from baseline to 2 hours after reperfusion of the portal vein (final - initial).
Baseline (start of surgery) and 2 hours after reperfusion of the portal vein

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Product Transfusions
Time Frame: During surgery
The number of units of packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate transfused during surgery. We had originally proposed to measure up until 72 hours after surgery, but we were not able to collect this data at all centers. Therefore, only blood product transfusions during surgery are reported.
During surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

University of Colorado, Denver
The Methodist Hospital Research Institute

Investigators

  • Principal Investigator: Michael P Bokoch, MD, PhD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 Major Dates

Study Start (Actual)

July 7, 2018

Primary Completion (Actual)

August 17, 2023

Study Completion (Actual)

September 14, 2023

Study Registration Dates

First Submitted

April 27, 2018

First Submitted That Met QC Criteria

May 11, 2018

First Posted (Actual)

May 23, 2018

Study Record Updates

Last Update Posted (Actual)

May 16, 2025

Last Update Submitted That Met QC Criteria

May 15, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-22384

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

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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