Clinical trial NCT03534141: Mild Hypothermia and Acute Kidney Injury in Liver Transplantation
Official title: Mild Hypothermia and Acute Kidney Injury in Liver Transplantation (MHALT) Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
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
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University of Colorado, Denver
name: The Methodist Hospital Research Institute
First posted: 2018-05-23
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Acute Kidney Injury (AKI)
timeFrame: 72 hours from the end of surgery
Secondary outcomes:
measure: Distribution of the Stages of Acute Kidney Injury (AKI)
timeFrame: 72 hours from the end of surgery
measure: Duration of Intensive Care Unit (ICU) Stay
timeFrame: Time from end of liver transplant to ICU discharge, approximately 1 to 3 days
measure: Duration of Hospital Stay
timeFrame: Time from liver transplant to hospital discharge, approximately 1-2 weeks.
measure: Patient Survival
timeFrame: up to 1 year
measure: Need for Renal Replacement Therapy
timeFrame: 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.
measure: Persistent Renal Dysfunction
timeFrame: 90 days and 1 year
measure: Serum Neutrophil Gelatinase-associated Lipocalin (NGAL)
timeFrame: Baseline (start of surgery) and 2 hours after reperfusion of the portal vein
measure: Urine Neutrophil Gelatinase-associated Lipocalin (NGAL)
timeFrame: Baseline (start of surgery) and 2 hours after reperfusion of the portal vein
Other outcomes:
measure: Blood Product Transfusions
timeFrame: During surgery
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
affiliation: University of California, San Francisco
name: Michael P Bokoch, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.
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.
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.