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
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-20
• Last Update Posted: 2023-12-27
• Disposition First Submitted: 2024-07-26

Recruitment & Eligibility

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

Inclusion Criteria

• Liver transplantation from a donor after neurologic determination of death

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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

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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
Incidence 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, will be used to define AKI.; A predefined subgroup analysis of this primary outcome will be performed in patients undergoing liver transplantation for hepatocellular carcinoma (HCC) with Model for End-stage Liver Disease exception points.

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, will be used to define the stage of AKI (Stage 1, 2, or 3).; A predefined subgroup analysis of this secondary outcome will be performed in patients undergoing liver transplantation for hepatocellular carcinoma (HCC) with Model for End-stage Liver Disease exception points.
Duration of intensive care unit (ICU) stay	up to 1 year	Time after liver transplantation until patient is discharged from the ICU to a regular hospital bed.
Need for renal replacement therapy	7 days, 30 days, and 1 year	Patient is receiving continuous renal replacement therapy or dialysis at the time of follow-up.
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.
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.
Duration of hospital stay	up to 1 year	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.

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