Mild Hypothermia and Acute Kidney Injury in Liver Transplantation

NCT03534141 | Terminated Results DMC FDA Device

• 1 other identifier: 17-22384
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 3

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.

Conditions

Cirrhosis; End Stage Liver Disease; Acute Kidney Injury; Liver Transplant; Complications; Chronic Kidney Diseases; Hepatitis c; Hepatitis B; NASH - Nonalcoholic Steatohepatitis; Alcoholic Cirrhosis; Hepatocellular Carcinoma

Keywords

Hypothermia; NGAL - Neutrophil Gelatinase-associated Lipocalin

Outcome Measures

Primary Outcomes (1)

• Acute Kidney Injury (AKI)

  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 Outcomes (8)

• Distribution of the Stages of Acute Kidney Injury (AKI)

  72 hours from the end of surgery

• Duration of Intensive Care Unit (ICU) Stay

  Time from end of liver transplant to ICU discharge, approximately 1 to 3 days

• Duration of Hospital Stay

  Time from liver transplant to hospital discharge, approximately 1-2 weeks.

• Patient Survival

  up to 1 year

• 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.

Other Outcomes (1)

• Blood Product Transfusions

  During surgery

Study Arms (2)

Mild hypothermia & Esophageal cooling/warming device

EXPERIMENTAL

The target core temperature is 34-35 °C.

Device: Esophageal cooling/warming device; Other: Mild hypothermia

Normothermia & Esophageal cooling/warming device

ACTIVE COMPARATOR

The target core temperature is 36.5-37.5 °C.

Device: Esophageal cooling/warming device; Other: Normothermia

Interventions

Esophageal cooling/warming device 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.

Also known as: EnsoETM, ECD - Esophageal Cooling Device

Mild hypothermia & Esophageal cooling/warming device; Normothermia & Esophageal cooling/warming device

Mild hypothermia OTHER

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.

Mild hypothermia & Esophageal cooling/warming device

Normothermia OTHER

After induction of anesthesia, the esophageal cooling/warming device and standard warming measures will be used to maintain normothermia throughout the operation.

Normothermia & Esophageal cooling/warming device

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Liver transplantation from a donor after neurologic determination of death

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• University of Colorado, Denver: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (3)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Related Publications (6)

• Niemann CU, Feiner J, Swain S, Bunting S, Friedman M, Crutchfield M, Broglio K, Hirose R, Roberts JP, Malinoski D. Therapeutic Hypothermia in Deceased Organ Donors and Kidney-Graft Function. N Engl J Med. 2015 Jul 30;373(5):405-14. doi: 10.1056/NEJMoa1501969.

  PMID: 26222557 BACKGROUND

• Angeli P, Gines P, Wong F, Bernardi M, Boyer TD, Gerbes A, Moreau R, Jalan R, Sarin SK, Piano S, Moore K, Lee SS, Durand F, Salerno F, Caraceni P, Kim WR, Arroyo V, Garcia-Tsao G; International Club of Ascites. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut. 2015 Apr;64(4):531-7. doi: 10.1136/gutjnl-2014-308874. Epub 2015 Jan 28. No abstract available.

  PMID: 25631669 BACKGROUND

• Niemann CU, Walia A, Waldman J, Davio M, Roberts JP, Hirose R, Feiner J. Acute kidney injury during liver transplantation as determined by neutrophil gelatinase-associated lipocalin. Liver Transpl. 2009 Dec;15(12):1852-60. doi: 10.1002/lt.21938.

  PMID: 19938135 BACKGROUND

• Kalasbail P, Makarova N, Garrett F, Sessler DI. Heating and Cooling Rates With an Esophageal Heat Exchange System. Anesth Analg. 2018 Apr;126(4):1190-1195. doi: 10.1213/ANE.0000000000002691.

  PMID: 29283916 BACKGROUND

• Karapanagiotou A, Dimitriadis C, Papadopoulos S, Kydona C, Kefsenidis S, Papanikolaou V, Gritsi-Gerogianni N. Comparison of RIFLE and AKIN criteria in the evaluation of the frequency of acute kidney injury in post-liver transplantation patients. Transplant Proc. 2014 Nov;46(9):3222-7. doi: 10.1016/j.transproceed.2014.09.161.

  PMID: 25420865 BACKGROUND

• Kellum JA, Zarbock A, Nadim MK. What endpoints should be used for clinical studies in acute kidney injury? Intensive Care Med. 2017 Jun;43(6):901-903. doi: 10.1007/s00134-017-4732-1. Epub 2017 Mar 2. No abstract available.

  PMID: 28255614 BACKGROUND

MeSH Terms

Conditions

Fibrosis; End Stage Liver Disease; Acute Kidney Injury; Renal Insufficiency, Chronic; Hepatitis C; Hepatitis B; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis, Alcoholic; Carcinoma, Hepatocellular; Hypothermia

Interventions

Hypothermia, Induced

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Hepadnaviridae Infections; DNA Virus Infections; Fatty Liver; Liver Cirrhosis; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Body Temperature Changes; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cryotherapy; Therapeutics

Results Point of Contact

• Title: Dr. Michael P. Bokoch, Principal Investigator
• Organization: University of California, San Francisco

Michael.Bokoch@ucsf.edu

415-476-8389

Study Officials

• Michael P Bokoch, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2018
• First Posted: May 23, 2018
• Study Start: July 7, 2018
• Primary Completion: August 17, 2023
• Study Completion: September 14, 2023
• Last Updated: May 16, 2025
• Results First Posted: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)