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Minocycline Administration During Human Liver Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02712775
Recruitment Status : Withdrawn (Study logistics)
First Posted : March 18, 2016
Last Update Posted : June 18, 2018
Sponsor:
Information provided by (Responsible Party):
Medical University of South Carolina

Brief Summary:
Liver transplantation is the sole therapy for end-stage liver diseases and acute liver failure in children and adults. However, use of this life-saving technique is limited due to a severe shortage of donor livers. The number of transplants currently performed is approximately one-third of the number needed to accommodate the more than 16,000 patients awaiting an organ in the US. Over 20% of patients on the liver transplant waiting list die prior to transplantation due to organ shortages. The median waiting time in 2011 was over 300 days. Poor immediate graft function and primary non function (PNF) are clinically significant events, especially in recipients of marginal livers (elderly donors, extended cold storage time, or steatosis). PNF has dramatic effects on patient morbidity and mortality, necessitating prolonged and expensive stays in intensive care units, and re-transplantation is the only life-saving therapy in patients with failing liver grafts due to PNF. This further exerts greater burden on the already scarce donor organ pool. Furthermore, biliary strictures and ischemic cholangiopathy, as a result of severe ischemia reperfusion injury, cause prolonged hospital stay, long-term complications, and increased costs. Targeted treatments, such as the one proposed in this application, will reduce the need for re-transplantation, reduce biliary injury, and potentially increase the number of donor organs available.

Condition or disease Intervention/treatment Phase
Liver Disease Drug: Minocycline (yes/no) Drug: Placebo Phase 4

Detailed Description:
Liver transplantation is the sole therapy for end-stage liver diseases in children and adults. However, use of this life-saving technique is limited due to a severe shortage of donor livers and, consequently, over 1500 patients/year on waiting lists die prior to transplantation due to organ shortages. Also, poor immediate graft function remains a persistent problem especially in recipients of marginal livers, and biliary strictures evolving from reperfusion injury cause prolonged hospital stay, increased health care costs, and increased mortality. Furthermore, hepatic cold storage and reperfusion in transplantation settings cause mitochondrial dysfunction in liver cells, which constitutes a great risk for primary nonfunction and initial poor function after liver transplantation. The tetracycline derivative minocycline is a safe and widely used antibiotic that possesses cytoprotective effects through prevention of mitochondrial dysfunction in a variety of disease models. Recently, we showed that minocycline also protects against graft dysfunction and failure after orthotopic rat liver transplantation and against cell death after ischemia-reperfusion to cultured rat hepatocytes. Minocycline treatment specifically prevented mitochondrial dysfunction and increased graft and animal survival by blocking necrotic and apoptotic death pathways. Clinical studies indicating severe deterioration of mitochondrial function in livers during preservation provide a strong impetus to investigate minocycline as an effective agent to decrease injury and improve graft function after human clinical transplantation.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Minocycline Administration During Human Liver Transplantation
Study Start Date : March 2016
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Minocycline
Experimental group will receive an infusion of minocycline, the investigational drug, through a needle in a vein in the arm at the dose of 200 mg at 1 h prior to transplantation and 100 mg 12 h and 24 h after transplantation. In addition, the donated liver will be flushed with 200 mg minocycline 1 h prior to transplantation.
Drug: Minocycline (yes/no)
Placebo Comparator: Saline
Placebo group will receive an infusion of saline, a placebo, through a needle in a vein in the arm according to the same schedule. In addition, the donated liver will be flushed with saline 1 h prior to transplantation.
Drug: Placebo
Saline




Primary Outcome Measures :
  1. AST [ Time Frame: 6 month ]
    AST is the primary endpoint our study is powered to detect. Peak AST >1500 IU/L is associated with clinical sequel of IRI such as severe graft dysfunction and complications.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All adult primary transplant recipients of solitary orthotopic liver transplants are considered for this study

Exclusion Criteria:

  • Pediatric patients, fulminant hepatic failures, split livers, living donor liver transplants, multiple organs, known tetracycline hypersensitivity, and re-transplant patients are excluded.

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): NCT02712775


Locations
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United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29401
Sponsors and Collaborators
Medical University of South Carolina
Investigators
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Principal Investigator: Kenneth Chavin, MD, PhD Medical University of South Carolina

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Responsible Party: Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT02712775    
Other Study ID Numbers: MCL-001
First Posted: March 18, 2016    Key Record Dates
Last Update Posted: June 18, 2018
Last Verified: March 2016
Additional relevant MeSH terms:
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Liver Diseases
Digestive System Diseases
Minocycline
Anti-Bacterial Agents
Anti-Infective Agents