The Effect and Safety Profile of Thymoglobulin® in Primary Cardiac Transplant Recipients
- Conditions
- Heart Transplantation
- Interventions
- Registration Number
- NCT03292861
- Lead Sponsor
- Cedars-Sinai Medical Center
- Brief Summary
This is a randomized, controlled, single center study to evaluate the efficacy of Thymoglobulin induction therapy in combination with Mycophenolate Mofetil, tacrolimus, and steroids in the prevention of CAV. Approximately half of the patients will be randomized to receive a total of 5 doses of Thymoglobulin during the study. The first dose of Thymoglobulin will be administered at 1.5 mg/kg via intravenous infusion over 6 hours immediately upon arrival to the ICU post-operation (day 1). Subsequent doses of 1.5 mg/kg will be administered on days 2, 3, 4, and 5 via IV infusion over 4 hours.
Mechanistic assays (T-reg cells, Lym subsets, B cell subsets, IL-1b, cytokines, TGFb, IL-21 to be drawn at Pre-transplant, 3, 6, 12 months post-transplant) will also be performed.
All patients will be followed and monitored according to standard of care protocols for heart transplant recipients at our center.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Thymoglobulin® Corticosteroids Thymoglobulin® (Genzyme) \[rabbit anti-thymocyte globulin (ATG)\] is a purified pasteurized, gamma immune globulin, obtained by immunization of rabbits with human thymocytes. This immunosuppressive product contains polyclonal cytotoxic antibodies directed against antigens expressed on human T-lymphocytes. Approximately half of the patients will be randomized to receive a total of 5 doses of Thymoglobulin during the study. The first dose of Thymoglobulin will be administered at 1.5 mg/kg via intravenous infusion over 6 hours immediately upon arrival to the ICU post-operation (day 1). Subsequent doses of 1.5 mg/kg will be administered on days 2, 3, 4, and 5 via IV infusion over 4 hours. In addition, there will be maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and cumulative dose of corticosteroids at 12 months post-transplantation Thymoglobulin® Thymoglobulin Thymoglobulin® (Genzyme) \[rabbit anti-thymocyte globulin (ATG)\] is a purified pasteurized, gamma immune globulin, obtained by immunization of rabbits with human thymocytes. This immunosuppressive product contains polyclonal cytotoxic antibodies directed against antigens expressed on human T-lymphocytes. Approximately half of the patients will be randomized to receive a total of 5 doses of Thymoglobulin during the study. The first dose of Thymoglobulin will be administered at 1.5 mg/kg via intravenous infusion over 6 hours immediately upon arrival to the ICU post-operation (day 1). Subsequent doses of 1.5 mg/kg will be administered on days 2, 3, 4, and 5 via IV infusion over 4 hours. In addition, there will be maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and cumulative dose of corticosteroids at 12 months post-transplantation Thymoglobulin® Mycophenolate Mofetil Thymoglobulin® (Genzyme) \[rabbit anti-thymocyte globulin (ATG)\] is a purified pasteurized, gamma immune globulin, obtained by immunization of rabbits with human thymocytes. This immunosuppressive product contains polyclonal cytotoxic antibodies directed against antigens expressed on human T-lymphocytes. Approximately half of the patients will be randomized to receive a total of 5 doses of Thymoglobulin during the study. The first dose of Thymoglobulin will be administered at 1.5 mg/kg via intravenous infusion over 6 hours immediately upon arrival to the ICU post-operation (day 1). Subsequent doses of 1.5 mg/kg will be administered on days 2, 3, 4, and 5 via IV infusion over 4 hours. In addition, there will be maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and cumulative dose of corticosteroids at 12 months post-transplantation Thymoglobulin® Tacrolimus Thymoglobulin® (Genzyme) \[rabbit anti-thymocyte globulin (ATG)\] is a purified pasteurized, gamma immune globulin, obtained by immunization of rabbits with human thymocytes. This immunosuppressive product contains polyclonal cytotoxic antibodies directed against antigens expressed on human T-lymphocytes. Approximately half of the patients will be randomized to receive a total of 5 doses of Thymoglobulin during the study. The first dose of Thymoglobulin will be administered at 1.5 mg/kg via intravenous infusion over 6 hours immediately upon arrival to the ICU post-operation (day 1). Subsequent doses of 1.5 mg/kg will be administered on days 2, 3, 4, and 5 via IV infusion over 4 hours. In addition, there will be maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and cumulative dose of corticosteroids at 12 months post-transplantation Thymoglobulin® Sirolimus Thymoglobulin® (Genzyme) \[rabbit anti-thymocyte globulin (ATG)\] is a purified pasteurized, gamma immune globulin, obtained by immunization of rabbits with human thymocytes. This immunosuppressive product contains polyclonal cytotoxic antibodies directed against antigens expressed on human T-lymphocytes. Approximately half of the patients will be randomized to receive a total of 5 doses of Thymoglobulin during the study. The first dose of Thymoglobulin will be administered at 1.5 mg/kg via intravenous infusion over 6 hours immediately upon arrival to the ICU post-operation (day 1). Subsequent doses of 1.5 mg/kg will be administered on days 2, 3, 4, and 5 via IV infusion over 4 hours. In addition, there will be maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and cumulative dose of corticosteroids at 12 months post-transplantation
- Primary Outcome Measures
Name Time Method Percentage of Participants With Composite Efficacy Failure at 12 Months 12 Months Composite efficacy failure is defined as development of de novo donor specific antibodies (measured by standardized alloantibody testing by Luminex and control sera, characterizing kinetics, specificities and relative binding strength) and ischemia on endomyocardial biopsy (characterized on biopsy by myocyte necrosis and/or regions of myocyte dropout) at 12 months post-transplant.
- Secondary Outcome Measures
Name Time Method Changes in biomarkers 12 months Correlations between significant changes in biomarkers and their relation to any significant differences in clinical outcomes
Number of patients who experience rejection 12 months Number of patients who experience acute cellular, antibody-mediated, hemodynamic compromise, and any-treated rejection within first 12 months after transplantation/
First rejection by ISHLT biopsy grading scale 12 months First acute cellular, antibody-mediated, hemodynamic compromise, and any-treated rejection by the ISHLT biopsy grading scale in the first 12 months post-transplantation
Time to first rejection 12 months Time to first acute cellular, antibody-mediated, hemodynamic compromise, and any-treated rejection within the first 12 months
Incidence of primary graft dysfunction (PGD) first 24 hours post-transplant The incidence of Primary Graft Dysfunction(PGD) in the first 24 hours post-transplant
Patient and graft survival 12 months Patient and graft survival at 12 months post-transplantation
Types of patients with fatal infectious complications 12 months The types of patients with fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation
Number of patients with fatal infectious complications 12 months The number of patients with fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation
Types of patients with non-fatal infectious complications 12 months Types of patients with non-fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation
Number of patients with non-fatal infectious complications 12 months Number of patients with non-fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation
Freedom from development of circulating antibodies 12 months Freedom from the development of circulating antibodies within the first 12 months post transplantation, where circulating antibodies include donor specific antibodies (DSA), non-specific antibodies, and non-human leukocyte antigen antibodies
Change in coronary maximal intimal thickness 12 months Change in coronary maximal intimal thickness at matched sites by intravascular ultrasound at 12 months
Changes in immune cell profiles 12 months Correlations between significant changes in immune cell profiles and biomarkers, and their relation to any significant differences in clinical outcomes
Number of episodes per patient 12 months Number of acute cellular, antibody-mediated, hemodynamic compromise and any-treated rejection episodes per patient within the first 12 months post-transplantation
Change in coronary intimal area 12 months Change in coronary intimal area at matched sites by intravascular ultrasound at 12 months
Change in coronary intimal volume 12 months Change in coronary intimal volume at matched sites by intravascular ultrasound at 12 months
Change in coronary vessel area 12 months Change in coronary vessel area at matched sites by intravascular ultrasound at 12 months
Change in coronary intimal index 12 months Change in coronary intimal index at matched sites by intravascular ultrasound at 12 months
Change in coronary percent atheroma volume 12 months Change in coronary percent atheroma volume at matched sites by intravascular ultrasound at 12 months
Maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and dose of corticosteroids 12 months Maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and cumulative dose of corticosteroids at 12 months post-transplantation
Number of hospital days per patient 3 months, 6 months, 12 months Number of hospital days per patient, both during the transplant period and during the post-transplant period at 3 months, 6 months, and 1 year
Number of patients requiring hospitalization 3 months, 6 months, 12 months Number of patients requiring hospitalization by 3 months, by 6 months, or by 1 year post-transplantation
Death/Re-transplant 12 months To describe between treatment groups the incidence of the composite primary endpoint of death/re-transplant at 12 months post-transplantation
Hemodynamic compromise rejection 12 months To describe between treatment groups the incidence of the composite primary endpoint of hemodynamic compromise rejection at 12 months post-transplantation. This is an ejection fraction of ≤ 30% or a 0.20 absolute decrease from baseline, and the need for inotropic agents OR a fractional shortening ≤ 20% or a 25% decrease from baseline, and the need for inotropic agents PLUS need for inotropic agents due to a Cardiac Index (CI) \< 2.0 L/min/m2 or a 25% decrease from baseline
Graft dysfunction 12 months To describe between treatment groups the incidence of the composite primary endpoint of graft dysfunction (ejection fraction less than or equal to 40% by echocardiography)at 12 months post-transplantation
Cellular rejection 12 months To describe between treatment groups the incidence of the composite primary endpoint of biopsy proven cellular rejection ≥2R at 12 months post-transplantation
Antibody mediated rejected 12 months To describe between treatment groups the incidence of the composite primary endpoint of biopsy proven antibody mediated rejection ≥AMR1 at 12 months post-transplantation
Cardiac Allograft Vasculopathy (CAV) 12 months To describe between treatment groups the incidence of cardiac allograft vasculopathy (CAV) (defined as a change ≥0.5mm in maximal intimal thickness (MIT) of the coronary arteries by intravascular ultrasound at 12 months as compared to baseline)
Any treated rejection 12 months To describe between treatment groups any treated rejection at 12 months
Trial Locations
- Locations (2)
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States