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

NCT00709293 | Withdrawn

• 1 other identifier: Thymoglobulin - Alejos
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Keywords

Ischemia Reperfusion Injury; Pediatric Heart Transplant; ATG; Induction Therapy

Study Arms (2)

1

PLACEBO COMPARATOR

Drug: Normal Saline

2

ACTIVE COMPARATOR

Drug: Anti-Thymocyte Globulin

Interventions

Anti-Thymocyte Globulin 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.

Also known as: ATG

2

Normal Saline 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.

1

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Mattel Children's Hospital at UCLA

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Reperfusion Injury

Interventions

Antilymphocyte Serum; Saline Solution

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Juan C Alejos, MD

  Department of Pediatrics, University of California Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: July 1, 2008
• First Posted: July 3, 2008
• Study Start: July 1, 2008
• Primary Completion: May 1, 2009
• Last Updated: June 18, 2013

Record last verified: 2013-06

Locations

US (1)