A Randomized Controlled Clinical Trial of Thymoglobulin® After Liver Transplantation

NCT02544113 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 15-943
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 4

Brief Summary

This is a 24-month, Phase II, multi-center, two-arm, randomized controlled study of adult patients receiving a single organ liver transplant from a deceased donor; the purpose being to determine the efficacy of Thymoglobulin® induction and delayed initiation of CNI in the long-term preservation of renal function after liver transplantation. This study is based on the outcomes of an earlier phase 1 pilot study which was performed at the Cleveland Clinic. This study will be conducted at 3 centers, with 110 subjects randomized 1:1 into two groups: Group 1 will receive Thymoglobulin® induction, (4.5 mg/Kg, in 3 doses of 1.5 mg/Kg/dose) with delayed initiation of CNI to begin on Day 10 post LT. Group 2 will receive early CNI initiation (to be started no later than Day 2 post LT), and no Thymoglobulin® induction (or any other antibody). All subjects will also receive a maintenance immunosuppressive regimen consisting of corticosteroids and mycophenolate mofetil (MMF) according to standard of practice in orthotopic liver transplantation (OLT). Subjects will be consented pre-transplant. Participation may last up to 12 months post OLT. There are 15 study-related visits which will be completed during standard of care (SOC) visits.

Conditions

Liver Failure

Outcome Measures

Primary Outcomes (1)

• The Incidence of Acute Kidney Injury (AKI) as Assessed by Change in Serum Creatinine From Baseline to 30 Days Post-transplant

  Change in serum creatinine from baseline to 30 days post-transplant. Higher values are associated with worse outcomes, and values greater than 0.3 mg/dL are suggestive of acute kidney injury.

  30 days post-transplant

Secondary Outcomes (2)

• Number of Participants Experiencing Acute Cellular Rejection

  30 days post OLT

• Graft Survival

  6 months post OLT

Study Arms (2)

Thymo

EXPERIMENTAL

Subjects randomized to the (Delay CNI) group will be treated with Thymoglobulin® (total dose of 4.5 mg/kg) administered in three doses; (each dose being 1.5 mg/kg - administered Day 0 \[after transplant\], Day 2, and Day 4 post transplant), along with CNI delay for 10 days. CNI will be initiated on postoperative (post-transplant) Day 10. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center.

Drug: Thymoglobulin

Control

PLACEBO COMPARATOR

Subjects randomized to the (Early CNI) group (Control group) will receive no antibody therapy for induction and will start CNI therapy on postoperative (post-transplant) Day 2. Subjects will also receive a maintenance immunosuppression regimen of corticosteroids and MMF in accordance with the standard practice at each clinical center.

Drug: Placebo

Interventions

Thymoglobulin DRUG

Treatment with thymoglobulin and delayed CNI post OLT

Also known as: Anti-thymocyte Globulin

Thymo

Placebo DRUG

Normal transplant immunosuppression

Control

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing deceased donor solitary liver transplantation
• Age 18-75 years at the time of transplantation
• Willingness and ability to comply with the study procedures
• Signed informed consent form
• For patients with Hepatocellular carcinoma as indication for OLT, (must be within the Milan Criteria)
• Hepatitis C, positive or negative, patients

You may not qualify if:

• Prior kidney transplantation
• Congenital or iatrogenic absence of one kidney
• Subjects on renal replacement therapy at the time of OLT
• MELD score \>34
• HIV positive patient
• Patient with current severe systemic infection
• History of bacterial peritonitis within 30 days prior to OLT
• Active infection or recent infection within 30 days prior to OLT
• Use of a calcineurin inhibitor continuously for more than 90 days within the past 6 months
• History of hypersensitivity to Thymoglobulin®, rabbits or tacrolimus
• Pregnant and/or nursing (lactating) females.
• Women of childbearing age who are unwilling to use effective contraception during the duration of the study, and for 30 days after study participation and/or last dose of Study Drug.

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (4)

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

University of Cincinnati College of Medicine

Cincinnati, Ohio, United States

Location

Cleveland Clinic (Main Campus)

Cleveland, Ohio, 44195, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Nair A, Coromina Hernandez L, Shah S, Zervos X, Zimmerman M, Sasaki K, Diago T, Hashimoto K, Fujiki M, Aucejo F, Bollinger J, Kaiser TL, Miller CM, Quintini C, Fung JJ, Eghtesad B. Induction Therapy With Antithymocyte Globulin and Delayed Calcineurin Inhibitor Initiation for Renal Protection in Liver Transplantation: A Multicenter Randomized Controlled Phase II-B Trial. Transplantation. 2022 May 1;106(5):997-1003. doi: 10.1097/TP.0000000000003904. Epub 2021 Jul 27.

  PMID: 34319926 DERIVED

MeSH Terms

Conditions

Liver Failure

Interventions

thymoglobulin; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr. Bijan Eghtesad
• Organization: Cleveland Clinic

eghtesb@ccf.org

216 444-9898

Study Officials

• Bijan Eghtesad

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Surgeon

Study Record Dates

• First Submitted: September 1, 2015
• First Posted: September 9, 2015
• Study Start: December 1, 2015
• Primary Completion: June 26, 2018
• Study Completion: January 3, 2020
• Last Updated: May 6, 2021
• Results First Posted: May 6, 2021

Record last verified: 2021-05

Locations

US (4)