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

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ClinicalTrials.gov Identifier: NCT03534141
Recruitment Status : Recruiting
First Posted : May 23, 2018
Last Update Posted : April 10, 2019
Sponsor:
Collaborator:
University of Colorado, Denver
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
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 Device: Esophageal cooling/warming device Other: Mild hypothermia Other: Normothermia Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Mild Hypothermia and Acute Kidney Injury in Liver Transplantation (MHALT) Trial
Actual Study Start Date : July 7, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
Experimental: Mild hypothermia & Esophageal cooling/warming device
The target core temperature is 34-35 °C.
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 Names:
  • EnsoETM
  • ECD - Esophageal Cooling Device

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.

Active Comparator: Normothermia & Esophageal cooling/warming device
The target core temperature is 36.5-37.5 °C.
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 Names:
  • EnsoETM
  • ECD - Esophageal Cooling Device

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




Primary Outcome Measures :
  1. Incidence of Acute Kidney Injury (AKI) [ Time Frame: 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 :
  1. Distribution of the Stages of Acute Kidney Injury (AKI) [ Time Frame: 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.


  2. Duration of intensive care unit (ICU) stay [ Time Frame: up to 1 year ]
    Time after liver transplantation until patient is discharged from the ICU to a regular hospital bed.

  3. Duration of hospital stay [ Time Frame: up to 1 year ]
    From the date of liver transplantation until the date patient is discharged from the hospital.

  4. Patient survival [ Time Frame: up to 1 year ]
    From the date of liver transplantation until the date of death from any cause.

  5. Need for renal replacement therapy [ Time Frame: 7 days, 30 days, and 1 year ]
    Patient is receiving continuous renal replacement therapy or dialysis at the time of follow-up.

  6. Persistent renal dysfunction [ Time Frame: 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.

  7. Serum neutrophil gelatinase-associated lipocalin (NGAL) [ Time Frame: 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.

  8. Urine neutrophil gelatinase-associated lipocalin (NGAL) [ Time Frame: 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.


Other Outcome Measures:
  1. Blood product transfusions [ Time Frame: 72 hours from the end of surgery ]
    The number of units of packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate transfused during the perioperative period.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Pulmonary hypertension
  • Subject unable to read, speak, or understand English (at UCSF only per IRB preference)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03534141


Contacts
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Contact: Michael P Bokoch, MD, PhD (650) 387-4314 Michael.Bokoch@ucsf.edu
Contact: Claus U Niemann, MD (415) 502-2162 Claus.Niemann@ucsf.edu

Locations
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United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Michael P Bokoch, MD, PhD    415-476-8389    Michael.Bokoch@ucsf.edu   
Contact: Claus U Niemann, MD    (415) 502-2162    Claus.Niemann@ucsf.edu   
United States, Colorado
University of Colorado Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Trevor L Nydam, MD    720-848-0833    Trevor.Nydam@ucdenver.edu   
Contact: Ivan Rodriguez, MD    (303) 724-2481    Ivan.2.Rodriguez@ucdenver.edu   
Principal Investigator: Trevor L Nydam, MD         
Sub-Investigator: Ana Fernandez-Bustamante, MD PhD         
Sponsors and Collaborators
University of California, San Francisco
University of Colorado, Denver
Investigators
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Principal Investigator: Michael P Bokoch, MD, PhD University of California, San Francisco

Publications:

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03534141     History of Changes
Other Study ID Numbers: 17-22384
First Posted: May 23, 2018    Key Record Dates
Last Update Posted: April 10, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of California, San Francisco:
Hypothermia
NGAL - Neutrophil Gelatinase-associated Lipocalin

Additional relevant MeSH terms:
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Wounds and Injuries
Hepatitis
Hepatitis A
Hepatitis C
Kidney Diseases
Carcinoma, Hepatocellular
Renal Insufficiency, Chronic
Hepatitis B
Fibrosis
Liver Cirrhosis
Liver Diseases
Acute Kidney Injury
Hypothermia
Fatty Liver
Non-alcoholic Fatty Liver Disease
End Stage Liver Disease
Liver Cirrhosis, Alcoholic
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Urologic Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms