Clinical trial NCT02635347: Remote Ischemic Conditioning (RIC) in Recipients of Brain Death Donor Livers - A Feasibility and Safety Study
Official title: Remote Ischemic Conditioning (RIC) in Recipients of Brain Death Donor Livers - A Feasibility and Safety Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Failure
Carcinoma, Hepatocellular
Keywords: Remote ischemic preconditioning
Remote ischemic perconditioning
Remote ischemic postconditioning
Remote ischemic conditioning
Orthotopic liver transplant
Brain Death Organ Donor
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2015-12-18
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will assess the feasibility of lower limb-ischemia induced Remote Ischemic Conditioning (RIC) in the perioperative period before, during, and after Orthotopic Liver Transplantation (OLT). Remote ischemic conditioning will consist of 3 cycles of 5 minutes of lower limb ischemia induced via a mid-thigh pneumatic tourniquet, followed by 5 minutes of reperfusion. Interventions will take place after anesthesia induction but before surgery, at the completion of the procedure, and on the mornings of post-operative days 1-4.

Detailed description: Orthotopic liver transplantation (OLT) is associated with a very high risk of complications. In a recent multi-center study of 450 patients, 79% had at least one complication and 63% had severe (Clavien-Dindo grade III or higher) complications. The number and severity of complications are associated with death within 30 days, hospital length of stay, graft and patient survival. Infections are the most common group of complications, followed by pulmonary, renal and liver graft dysfunction. Interventions that decrease these complications after OLT are likely to improve clinical outcomes.

Remote ischemic conditioning is an innate biological phenomenon wherein a brief single or repetitive ischemic stimulus in an organ or tissue such as skeletal muscle induce protection in remote/distant organs against ischemia and other noxious stimuli. This effect can be induced by inflating a pneumatic tourniquet on a leg or arm for a few minutes (usually 5-10) and subsequently deflating to allow reperfusion. This process is usually repeated 3-4 times to ensure an adequate dose of the conditioning stimulus. The conditioning stimulus could be applied before (Preconditioning), concurrent with (Perconditioning), or soon after the index noxious/ischemic insult (Postconditioning).

The goal of this study is to assess the feasibility, patient acceptance, and safety of RIC in liver recipients. In addition, the investigators will obtain data on posttransplant complications. Information obtained from this study will help guide the design of a future randomized, controlled trial to test the benefit of RIC in liver recipients.

Eligibility criteria: Inclusion Criteria:

* Adults (\> 18 years of age) with acute and chronic liver failure requiring liver transplants or patients undergoing transplantation for hepatocellular carcinoma.
* Both sexes
* Written consent to participate in the study

Exclusion Criteria:

* \< 18 years of age
* Recipients of split livers
* Retransplantation
* Recipients of livers combined with other organs
* Recipients of livers from cardiac death donors
* Lower extremity amputees
* History of peripheral vascular disease
* Patients taking sulfonylurea anti-diabetic agents at the time of transplant
* Patients taking nitrates at the time of transplant
* Body mass index \> 45
* Pregnant patients
* Patients in whom complete lower extremity ischemia is not achieved despite maximum tourniquet inflation to 250 mmHg during the first intervention
* Patients with lower extremity paralysis

Primary outcomes:
measure: Percentage of Participants Completing Entire Intervention Protocol
timeFrame: Pre-op - Post-op day 4
Secondary outcomes:
measure: Intervention-related Pain Score
timeFrame: Post-op days 1-4
measure: Withdrawal of Consent Due to Pain
timeFrame: Pre-op - Post-op day 7
measure: Percentage of Participants Who Developed Early Allograft Dysfunction (EAD)
timeFrame: Post-op days 0-7
measure: Percentage of Participants Who Developed Prolonged Respiratory Insufficiency (PRI)
timeFrame: Post-op days 0-7
measure: Percentage of Participants Who Developed Acute Kidney Injury (AKI) Stages 2 or 3
timeFrame: Post-op days 0-7
measure: Time to Dialysis Discontinuation
timeFrame: Post-op days 0-90
measure: Presence of Clavien-Dindo Grade IIIb or Higher Complications
timeFrame: Post-op days 0-30
measure: Clavien-Dindo Grade IIIb or Higher - Number of Complications
timeFrame: Post-op days 0-30
measure: Intensive Care Unit (ICU) Length of Stay (LOS)
timeFrame: Post-op days 0 up to 90 days
measure: Hospital LOS
timeFrame: Post-op days 0 up to 90 days
measure: Liver Allograft Survival
timeFrame: Post-op day 90
measure: Patient Survival
timeFrame: Post-op day 90
measure: Number of Subjects Not Completing Intervention Protocol
timeFrame: Pre-op - Post-op day 4
Other outcomes:
Locations:
city: Newark
country: United States
facility: Rutgers University - University Hospital
state: New Jersey
Study officials:
affiliation: Rutgers University
name: Baburao Koneru, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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