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NCT03534141: MHALT

Mild Hypothermia and Acute Kidney Injury in Liver Transplantation

Terminated NA Results posted Last updated 16 May 2025
What this trial tests

NA trial testing Esophageal cooling/warming device in Cirrhosis in 175 participants. Terminated before completion.

Timeline
7 July 2018
Primary endpoint
17 August 2023
14 September 2023

Quick facts

Lead sponsorUniversity of California, San Francisco
PhaseNA
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposeprevention
Enrollment175
Start date7 July 2018
Primary completion17 August 2023
Estimated completion14 September 2023
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of California, San Francisco

Who can join

18 and older, any sex, with Cirrhosis or End Stage Liver Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Acute Kidney Injury (AKI) Primary · 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.

GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device56
Normothermia & Esophageal Cooling/Warming Device47
Distribution of the Stages of Acute Kidney Injury (AKI) Secondary · 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: increas

GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device30
Normothermia & Esophageal Cooling/Warming Device38
Mild Hypothermia & Esophageal Cooling/Warming Device32
Normothermia & Esophageal Cooling/Warming Device20
Mild Hypothermia & Esophageal Cooling/Warming Device13
Normothermia & Esophageal Cooling/Warming Device9
Mild Hypothermia & Esophageal Cooling/Warming Device11
Normothermia & Esophageal Cooling/Warming Device18
Duration of Intensive Care Unit (ICU) Stay Secondary · 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.

GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device360 – 70
Normothermia & Esophageal Cooling/Warming Device3719 – 68
Duration of Hospital Stay Secondary · 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.

GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device75 – 9
Normothermia & Esophageal Cooling/Warming Device75 – 10
Patient Survival Secondary · up to 1 year

From the date of liver transplantation until the date of death from any cause.

GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device81
Normothermia & Esophageal Cooling/Warming Device78
Need for Renal Replacement Therapy Secondary · 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).

Renal replacement therapy within 72 hours after liver transplant.
GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device8
Normothermia & Esophageal Cooling/Warming Device13
Renal replacement therapy at 30 days after liver transplant.
GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device8
Normothermia & Esophageal Cooling/Warming Device5
Renal replacement therapy at 1 year after liver transplant.
GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device7
Normothermia & Esophageal Cooling/Warming Device9
Persistent Renal Dysfunction Secondary · 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).

Persistent renal dysfunction at 90 days after liver transplant.
GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device24
Normothermia & Esophageal Cooling/Warming Device25
Persistent renal dysfunction at 1 year after liver transplant.
GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device28
Normothermia & Esophageal Cooling/Warming Device32
Serum Neutrophil Gelatinase-associated Lipocalin (NGAL) Secondary · 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).

GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device20.81.8 – 61.4
Normothermia & Esophageal Cooling/Warming Device26.157.0 – 44.9
Urine Neutrophil Gelatinase-associated Lipocalin (NGAL) Secondary · 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).

GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device156.38.2 – 491.7
Normothermia & Esophageal Cooling/Warming Device81.855.8 – 250.2
Blood Product Transfusions Secondary · During surgery

The number of units of packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate transfused during surgery. We had originally proposed to measure up until 72 hours after surgery, but we were not able to collect this data at all centers. Therefore, only blood product transfusions during surgery are reported.

Packed red blood cells
GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device41 – 7
Normothermia & Esophageal Cooling/Warming Device51 – 8
Fresh frozen plasma
GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device8.53 – 14
Normothermia & Esophageal Cooling/Warming Device93 – 18
Platelets
GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device20 – 2
Normothermia & Esophageal Cooling/Warming Device20 – 3
Cryoprecipitate
GroupValue95% CI
Mild Hypothermia & Esophageal Cooling/Warming Device00 – 1
Normothermia & Esophageal Cooling/Warming Device00 – 1

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were assessed from the time of enrollment until the end of liver transplantation surgery, with the exception of surgical site infection which was assessed until 2 weeks after surgery. Serious adverse events were assessed until 2 weeks after surgery. Deaths were assessed for up to 1 year (see Outcome Measures: Patient survival).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Mild Hypothermia & Esophageal Cooling/Warming Device
Serious: 5/86 (6%)
Deaths: 5/86
Normothermia & Esophageal Cooling/Warming Device
Serious: 3/85 (4%)
Deaths: 7/85

Serious adverse events (4 terms)

ReactionSystemMild Hypothermia & Esophag…Normothermia & Esophageal …
Intraoperative cardiac arrestCardiac disorders
Primary non-function of the liverHepatobiliary disorders
Inferior vena cava thrombusBlood and lymphatic system disorders
Disseminated fungal infection leading to deathInfections and infestations
Other adverse events (16 terms — click to expand)

ReactionSystemMild Hypothermia & Esophag…Normothermia & Esophageal …
Bleeding (significant) with refractory severe coagulopathyBlood and lymphatic system disorders
Surgical bleeding, severeInjury, poisoning and procedural complications
Oropharyngeal, dental, or esophageal traumaInjury, poisoning and procedural complications
Cardiac arrhythmiaCardiac disorders
Postreperfusion syndromeHepatobiliary disorders
Esophageal temperature management device problemProduct Issues
Surgical site infectionInfections and infestations
Hypothermia, severeGeneral disorders
Myocardial ischemiaCardiac disorders
Electrolytes, overcorrection of hyponatremiaRenal and urinary disorders
Portal vein thrombusBlood and lymphatic system disorders
Drug errorInjury, poisoning and procedural complications
Traumatic central line insertionInjury, poisoning and procedural complications
Cardiovascular event, non-seriousCardiac disorders
Bleeding, upper gastrointestinal with esophageal temperature management device insertionGastrointestinal disorders
Perforation or damage to esophageal temperature management deviceProduct Issues

Most-reported serious reactions: Intraoperative cardiac arrest, Primary non-function of the liver, Inferior vena cava thrombus, Disseminated fungal infection leading to death.

Data from ClinicalTrials.gov NCT03534141 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Perioperative Acute Kidney Injury.
    Gumbert SD, Kork F, Jackson ML, Vanga N, et al · · 2020 · cited 209× · PMID 31687986 · DOI 10.1097/aln.0000000000002968
  2. Lipocalin 2-not only a biomarker: a study of current literature and systematic findings of ongoing clinical trials.
    Asaf S, Maqsood F, Jalil J, Sarfraz Z, et al · · 2023 · cited 38× · PMID 36529828 · DOI 10.1007/s12026-022-09352-2
  3. Vasopressin Is Not Associated With Severe Kidney Injury in Liver Transplantation: A Propensity Score-adjusted Analysis.
    Antonucci E, Bokoch MP, Adelmann D, Kolodzie K, et al · · 2025 · PMID 40406183 · DOI 10.1097/txd.0000000000001814

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Other recruiting trials for Cirrhosis

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing