Mild Hypothermia and Acute Kidney Injury in Liver Transplantation

Hepatocellular Carcinoma Clinical Trial

— MHALT  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03534141
• Other study ID #: 17-22384
• Status: Terminated
• Phase: N/A
• Start date: July 7, 2018
• Est. completion date: September 14, 2023

Study information

• Verified date: December 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 171
• Est. completion date: September 14, 2023
• Est. primary completion date: August 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Alcoholic Cirrhosis
• Chronic Kidney Diseases
• Cirrhosis
• End Stage Liver Disease
• Fatty Liver
• Fibrosis
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis c
• Hepatocellular Carcinoma
• Hypothermia
• Kidney Diseases
• Liver Cirrhosis
• Liver Cirrhosis, Alcoholic
• Liver Diseases
• Liver Transplant; Complications
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease
• Renal Insufficiency, Chronic
• Wounds and Injuries

Intervention

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

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Houston Methodist Hospital	Houston	Texas
United States	University of California, San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	The Methodist Hospital Research Institute, University of Colorado, Denver

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood product transfusions	The number of units of packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate transfused during the perioperative period.	72 hours from the end of surgery
Primary	Incidence of Acute Kidney Injury (AKI)	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.	72 hours from the end of surgery
Secondary	Distribution of the Stages of Acute Kidney Injury (AKI)	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.	72 hours from the end of surgery
Secondary	Duration of intensive care unit (ICU) stay	Time after liver transplantation until patient is discharged from the ICU to a regular hospital bed.	up to 1 year
Secondary	Duration of hospital stay	From the date of liver transplantation until the date patient is discharged from the hospital.	up to 1 year
Secondary	Patient survival	From the date of liver transplantation until the date of death from any cause.	up to 1 year
Secondary	Need for renal replacement therapy	Patient is receiving continuous renal replacement therapy or dialysis at the time of follow-up.	7 days, 30 days, and 1 year
Secondary	Persistent renal dysfunction	Presence of a reduction in GFR by = 25 mL/min or = 50% from baseline at the time of follow-up.	90 days and 1 year
Secondary	Serum neutrophil gelatinase-associated lipocalin (NGAL)	Change in serum NGAL levels from baseline to 2 hours after reperfusion of the portal vein.	Baseline (start of surgery) and 2 hours after reperfusion of the portal vein
Secondary	Urine neutrophil gelatinase-associated lipocalin (NGAL)	Change in urine NGAL levels from baseline to 2 hours after reperfusion of the portal vein.	Baseline (start of surgery) and 2 hours after reperfusion of the portal vein