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)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2010 by Cedars-Sinai Medical Center.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by:
Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT01157949
First received: July 7, 2010
Last updated: NA
Last verified: May 2010
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Cardiac Allograft Vasculopathy
Drug: Thymoglobulin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Cedars-Sinai Medical Center:

Estimated Enrollment: 116
Study Start Date: November 2010
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Thymoglobulin
    Study patients will receive 1.5 mg/kg/day intravenously for 5 days.
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01157949

Locations
United States, California
Cedars-Sinai Medical Center Not yet recruiting
Beverly Hills, California, United States, 90211
Contact: Matt Kawano       matt.kawano@cshs.org   
Principal Investigator: Jon Kobashigawa, MD         
Sponsors and Collaborators
Cedars-Sinai Medical Center
Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Jon A. Kobashigawa, MD, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT01157949     History of Changes
Other Study ID Numbers: MA-1007-1
Study First Received: July 7, 2010
Last Updated: July 7, 2010
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 28, 2014