Mild Hypothermia and Acute Kidney Injury in Liver Transplantation

Not Applicable

Terminated

• Conditions: NASH - Nonalcoholic Steatohepatitis; Cirrhosis; Liver Transplant; Complications; Hepatitis B; End Stage Liver Disease; Acute Kidney Injury; Chronic Kidney Diseases; Hepatitis c; Alcoholic Cirrhosis; Hepatocellular Carcinoma
• Interventions: Device: Esophageal cooling/warming device; Other: Normothermia; Other: Mild hypothermia

• Registration Number: NCT03534141
• Lead Sponsor: University of California, San Francisco

Brief Summary

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.

Detailed Description

This study is a single-blinded, 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 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 Timeline

• Study First Submitted: 2018-04-27
• Study First Submitted QC: 2018-05-11
• Study First Posted: 2018-05-23
• Study Start: 2018-07-07
• Primary Completion: 2023-08-17
• Study Completion: 2023-09-14
• Disposition First Submitted: 2024-07-26
• Results First Submitted: 2024-12-11
• Status Verified: 2025-05
• Results First Submitted QC: 2025-05-15
• Last Update Submitted: 2025-05-15
• Results First Posted: 2025-05-16
• Disposition First Posted: 2025-05-16
• Last Update Posted: 2025-05-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 171

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normothermia & Esophageal cooling/warming device	Esophageal cooling/warming device	The target core temperature is 36.5-37.5 °C.
Normothermia & Esophageal cooling/warming device	Normothermia	The target core temperature is 36.5-37.5 °C.
Mild hypothermia & Esophageal cooling/warming device	Esophageal cooling/warming device	The target core temperature is 34-35 °C.
Mild hypothermia & Esophageal cooling/warming device	Mild hypothermia	The target core temperature is 34-35 °C.

Primary Outcome Measures

Name	Time	Method
Acute Kidney Injury (AKI)	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.

Secondary Outcome Measures

Name	Time	Method
Distribution of the Stages of Acute Kidney Injury (AKI)	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.
Duration of Intensive Care Unit (ICU) Stay	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.
Duration of Hospital Stay	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.
Patient Survival	up to 1 year	From the date of liver transplantation until the date of death from any cause.
Persistent Renal Dysfunction	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).
Serum Neutrophil Gelatinase-associated Lipocalin (NGAL)	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).
Need for 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.	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).
Urine Neutrophil Gelatinase-associated Lipocalin (NGAL)	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).

Trial Locations

Locations (3)

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States