A Study to Compare the Effectiveness of a Drug That Suppresses the Immune System Called Thymoglobulin® in Preventing the Development of a Disease That Affects the Majority of Heart Transplant Recipients Called Cardiac Allograft Vasculopathy (CAV)

A Randomized Study to Assess the Effect and Safety Profile of Thymoglobulin® for the Prevention of Cardiac Allograft Vasculopathy in Primary Cardiac Transplant Recipients: A 12-month, Single Center, Randomized, Open-label Study of Efficacy Comparing Immediate Treatment With and Without Thymoglobulin® 1.5 mg/kg/d for 5 Consecutive Days in Heart Transplant Recipients.

The purpose of this study is to test the hypothesis that administering Thymoglobulin® induction therapy early after transplant prevents the development of cardiac allograft vasculopathy (CAV). CAV accounts for a significant number of deaths in cardiac recipients after the first year of transplant. At 5 years post-transplant 30% of the deaths are due to CAV. With the exception of re-transplantation the available treatments for CAV are only effective at inhibiting its progression.

CAV involves only the allograft and spares the native arteries, suggesting an immunologic basis for the disease. However, both immunological and non-immunological factors contribute to the development of CAV. The established immunological risk factors are recurrent rejection and humoral/antibody-mediated rejection (AMR). Non-immunological risk factors identified include preservation injury, the cause of donor death, donor graft ischemic time, and cytomegalovirus infection1. It is hypothesized that these factors increase the risk of developing CAV by causing early endothelial damage to the graft, which then could promote increased lymphocyte-endothelial interactions and the production of anti-endothelial antibodies2. The investigators hypothesized that Thymoglobulin induction therapy would prevent the development of CAV because its polyclonal nature allows Thymoglobulin to target all the potential mechanisms that contribute to the development of CAV-T-cell activation, B-cell activation, antibody formation, induction of tolerance, and modulation of lymphocyte-endothelium interactions3. Because the mechanism by which Thymoglobulin affects the immune system are still poorly understood, the investigators will also study how Thymoglobulin changes the immune system over time in the heart transplant recipient as a secondary objective.

Study Overview

• Status: Withdrawn
• Conditions: Cardiac Allograft Vasculopathy
• Intervention / Treatment: Drug: Thymoglobulin

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must be undergoing their first allograft transplant
• Men and non-pregnant women must be 18 to 70 years old
• Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to transplantation. The sensitivity must be equal to at least 50 mIU/mL. (Urine test is allowed in addition to serum test in patients where serum results are delayed).
• Women of childbearing potential must use two reliable forms of contraception simultaneously. Effective contraception must be used before beginning study drug therapy, and for 4 months following discontinuation of study drug therapy.
• Subjects must be willing and be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

Exclusion Criteria:

• Previous organ transplants
• Patients receiving multiple organs
• Patients > 250 lbs or 114 kgs
• Patients requiring VAD upon completion of transplantation surgery. [Patients who require LVADs prior to surgery may be enrolled as long as no presurgery immunosuppressives (see list in Appendix B) were administered.]
• Women lactating, pregnant, or of childbearing potential, not using, or who are unwilling to use two reliable forms of contraception simultaneously during the study.
• Men who are not using a reliable contraceptive method
• History of a psychological illness or condition which would interfere with the patient's ability to understand the requirements of the study
• White blood cell count ≤ 2500/mm3, or platelets ≤ 50,000/mm3, or hemoglobin ≤ 6g/dL
• HIV-1, HTLV-1, chronic Hepatitis B, or chronic Hepatitis C infection
• Documented or strong suspicion for pre-operative active infection that has not yet been adequately treated with the recommended course of antimicrobial therapy
• Presence of any chronic myelosuppressive disease or agent that has resulted in either chronic leucopenia or chronic thrombocytopenia
• Active peptic ulcer disease
• Patients who have received within the past 30 days or require concomitant treatment with other investigational drugs (except for those listed in section 8.6 "Concomitant treatment") or immunosuppressive medications that are prohibited for this study (Appendix B)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Study withdrawn	Drug: Thymoglobulin; Study patients will receive 1.5 mg/kg/day intravenously for 5 days.
Placebo Comparator: Withdrawn; Study withdrawn	Drug: Thymoglobulin; Study patients will receive 1.5 mg/kg/day intravenously for 5 days.

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Collaborators: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Anticipated): November 1, 2013
• Study Completion (Actual): January 10, 2018

Study Registration Dates

• First Submitted: July 7, 2010
• First Submitted That Met QC Criteria: July 7, 2010
• First Posted (Estimate): July 8, 2010

Study Record Updates

• Last Update Posted (Actual): March 14, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Thymoglobulin
• Other Study ID Numbers: MA-1007-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No