Intraoperative Versus Postoperative Thymoglobulin in Lung Transplantation

A Prospective Single Center Randomized Trial of Intraoperative Versus Postoperative Thymoglobulin in Lung Transplantation.

The purpose of this study is to take a population of lung transplant recipients who meet UCLA criteria for induction chemotherapy with thymoglobulin and prospectively study weather giving the first dose intraoperatively versus postoperatively makes a difference with how patients do during and after lung transplantation.

Study Overview

• Status: Withdrawn
• Conditions: Lung Transplant
• Intervention / Treatment: Drug: thymoglobulin (intraoperative); Drug: thymoglobulin (postoperative)

Detailed Description

The purpose of this study is to take a population of lung transplant recipients who meet UCLA criteria for induction chemotherapy with thymoglobulin and prospectively study weather giving the first dose intraoperatively versus postoperatively makes a difference with how patients do during and after lung transplantation. In addition, these cohorts will be compared to patients who do not qualify for thymoglobulin and receive either an alternative agent or no agent. The primary endpoint is primary graft dysfunction. We will also evaluate several other early and late end points such as ventilator days, ICU/hospital days, acute/chronic rejection, infection, CT chest abnormalities, and survival.

We will also collect donor lung tissue and lavage fluid for measurement of various proteins and receptor expression at two time points: (1) prior to implementation and dosing of induction chemotherapy and (2) after transplantation (following a course of induction chemotherapy). This will allow us to possibly make a connection between the profiles of the various proteins and receptors and the clinical outcomes, depending on weather the patient has received induction chemotherapy, starting intraoperatively or postoperatively.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1690
      • Departments of Pulmonary and Critical Care, Cardiothoracic Surgery and Infectious Diseases at David Geffen School of Medicine at UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• On a voluntary basis, all patients eligible for bilateral lung transplantation between the ages of 18-65 years (inclusive)

Exclusion Criteria:

• Have any known allergy to horse or rabbit antithymocyte polyclonal agents
• Have a preoperative platelet count less then 100,000/mm3
• Are recipients of multiple organ transplants (either simultaneous or sequential)
• Are recipients of a single lung transplantation
• Have a contraindication to rabbit antithymocyte globulin based on judgement of the investigators (i.e. bleeding diathesis or overwhelming risk of intense immunosuppression) including the following patients: greater than 65 years of age, prior diagnosis of malignancy (with the exception skin malignancies), underlying suppurative lung disease (i.e. bronchiectasis, cystic fibrosis, etc.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: thymoglobulin (intraoperative); we plan to blindly randomize these 25 lung transplant patients to intraoperative dosing of thymoglobulin followed by 3 additional postoperative doses (the first of these 3 postoperative doses will be placebo)	Drug: thymoglobulin (intraoperative); All patients (Arm I and Arm II) will receive 3 doses of thymoglobulin at 1.5mg/kg IV over 6 hours; only the timing of the medication is being altered. Each arm will also receive a single placebo dose. Arm I will receive thymoglobulin intraoperatively followed by a postoperative placebo dose and two subsequent thymoglobulin doses.; Other Names: thymoglobulin
Placebo Comparator: thymoglobulin (postoperative dosing); We plan to blindly randomize these 25 lung transplant patients to 3 postoperative doses of thymoglobulin (the intraoperative dose will be placebo)	Drug: thymoglobulin (postoperative); All patients (Arm I and Arm II) will receive 3 doses of thymoglobulin at 1.5mg/kg IV over 6 hours; only the timing of the medication is being altered. Each arm will also receive a single placebo dose. Arm II will receive placebo intraoperatively followed by 3 postoperative doses of thymoglobulin.; Other Names: thymoglobulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Graft Dysfunction	the definition for primary graft dysfunction is established and will be used to determine the grade of primary graft dysfunction at 4 time points after lung transplantation	paO2/FiO2 ratio at post transplant, 24 hr, 48 hr, and 72 hr time points

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Genzyme, a Sanofi Company
• Investigators: Principal Investigator: Rajan Saggar, MD, Pulmonology & Critical Care at UCLA

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2006
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: December 28, 2007
• First Submitted That Met QC Criteria: December 28, 2007
• First Posted (Estimate): January 14, 2008

Study Record Updates

• Last Update Posted (Actual): September 10, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: lung transplantation; ATG; rabbit thymoglobulin; reperfusion lung injury; primary graft dysfunction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Thymoglobulin; Antilymphocyte Serum
• Other Study ID Numbers: ATG in Lung Transplantation