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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Phase
- Phase 3
Contacts et emplacements
Lieux d'étude
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California
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Beverly Hills, California, États-Unis, 90211
- Cedars-Sinai Medical Center
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La 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)
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Comparateur actif: Study withdrawn
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Study patients will receive 1.5 mg/kg/day intravenously for 5 days.
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Comparateur placebo: Withdrawn
Study withdrawn
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Study patients will receive 1.5 mg/kg/day intravenously for 5 days.
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Anticipé)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- MA-1007-1
Informations sur les médicaments et les dispositifs, documents d'étude
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Essais cliniques sur Thymoglobulin
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Genzyme, a Sanofi CompanyRésiliéSyndrome myélodysplasique (SMD)Allemagne, Royaume-Uni, France, Pays-Bas
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National Institute of Allergy and Infectious Diseases...National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Clinical...ComplétéDiabète sucré, type ISuède, Norvège