Role of Intraoperative Thymoglobulin in Decreasing Ischemia-Reperfusion Injury in Pediatric Heart Transplant Recipients

NCT ID: NCT00709293

Last Updated: 2013-06-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31

Brief Summary

The restoration of normal blood flow following a period of ischemia may result in ischemia / reperfusion injury (I/RI), which is characterized by inflammation and oxidative damage to tissues. Varying degrees of I/RI occur upon reperfusion of a donor heart after cold storage. Medications containing antibodies against immune cells have been used for many years as powerful immunosuppressants. These medications, called polyclonal antibody preparations, are generally only used immediately following transplantation and/or to treat rejection. At our institution, one such antibody preparation (Thymoglobulin) is used in most pediatric heart transplant recipients for 3-5 days immediately after transplantation. Because standard immunosuppressive medications (called calcineurin inhibitors) are toxic to the kidneys, the use of Thymoglobulin allows us to delay the initiation of calcineurin inhibitors until the kidneys of completely recovered from the shock of the transplant surgery.

We hypothesize that Thymoglobulin may be beneficial in reducing the damage caused by I/RI. Thus, the present study seeks to evaluate the effectiveness of an intra-operative dose of Thymoglobulin (in addition to the standard doses post-operatively) at reducing the effects of I/RI. The study will be a double-bind placebo-controlled trial involving 20 subjects. Biologic markers for I/RI will be assessed at periodic intervals for six months post-transplantation. Subjects receiving intra-operative doses of Thymoglobulin will be compared to the controls in order to assess the effectiveness of intra-operative Thymoglobulin in ameliorating the effects of I/RI.

Conditions

Ischemia Reperfusion Injury; Heart Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

1

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: DRUG

Normal saline will be utilized as a placebo comparator. It will be infused in the same fashion as the Thymoglobulin in the intervention arm.

2

Group Type: ACTIVE_COMPARATOR

Anti-Thymocyte Globulin

Intervention Type: DRUG

Thymoglobulin (1.5 mg/kg body weight) will be infused through a peripheral intravenous line over a minimum of 6 hours. The infusion will be started at the time of donor visualization (once it is confirmed the transplant is proceeding). The peri-operative nurse or anesthesiologist will be responsible for drug infusion.

Interventions

Anti-Thymocyte Globulin

Thymoglobulin (1.5 mg/kg body weight) will be infused through a peripheral intravenous line over a minimum of 6 hours. The infusion will be started at the time of donor visualization (once it is confirmed the transplant is proceeding). The peri-operative nurse or anesthesiologist will be responsible for drug infusion.

Intervention Type: DRUG

Normal Saline

Normal saline will be utilized as a placebo comparator. It will be infused in the same fashion as the Thymoglobulin in the intervention arm.

Intervention Type: DRUG

Other Intervention Names

ATG

Eligibility Criteria

Inclusion Criteria

• Pediatric population (ages 0-21 years)
• End-stage cardiac disease requiring heart transplantation
• Approval for listing by the UCLA Heart Transplant Committee

Exclusion Criteria

• Prior documented Thymoglobulin allergy/adverse reaction
• History of or current diagnosis of lymphoma
• Documented lymphopenia
• Documented Thrombocytopenia
• Pregnancy

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Juan Alejos

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juan C Alejos, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Pediatrics, University of California Los Angeles

Locations

Mattel Children's Hospital at UCLA

Los Angeles, California, United States

Countries

United States

Other Identifiers

Thymoglobulin - Alejos

Identifier Type: -

Identifier Source: org_study_id