Heart Transplantation Clinical Trial
Official title:
A Pilot Randomized Study to Assess the Effect and Safety Profile of Thymoglobulin® 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
Verified date | November 2023 |
Source | Cedars-Sinai Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Enrolling by invitation |
Enrollment | 60 |
Est. completion date | October 31, 2025 |
Est. primary completion date | October 31, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria for Study Entry: 1. Subjects must be undergoing their first allograft transplant 2. Men and non-pregnant women must be 18 to 70 years old 3. 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) 4. Men with a female partner of child bearing age and 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. 5. Subjects must be willing and capable of understanding the purpose and risks of the study, and must sign a statement of informed consent 6. Subjects with a Creatinine < 2.0 mg/dl at time of transplant Exclusion Criteria for Study Entry: 1. Allergy to Thymoglobulin-Thymoglobulin is contraindicated in patients with history of allergy or anaphylaxis to rabbit proteins or to any product excipients, or who have active acute or chronic infections which contraindicate any additional immunosuppression 2. Previous organ transplants 3. Patients receiving multiple organs 4. Patients with a BMI higher than 35 5. Patients with PRA = 25% 6. Patients requiring VAD upon completion of transplantation surgery. 7. HIV-1, HTLV-1, chronic Hepatitis B, or chronic Hepatitis C infection 8. Documented or strong suspicion for pre-operative active infection that has not yet been adequately treated with the recommended course of antimicrobial therapy 9. Presence of any chronic myelosuppressive disease or agent that has resulted in either chronic leucopenia or chronic thrombocytopenia 10. Active peptic ulcer disease and active GI bleeding 11. 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") 12. Patients with a history of AL amyloidosis (TTR amyloids) are permitted |
Country | Name | City | State |
---|---|---|---|
United States | Cedars-Sinai Medical Center | Los Angeles | California |
United States | Kaiser Permanente Los Angeles Medical Center | Los Angeles | California |
Lead Sponsor | Collaborator |
---|---|
Cedars-Sinai Medical Center | Genzyme, a Sanofi Company |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percentage of Participants With Composite Efficacy Failure at 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. | 12 Months | |
Secondary | Changes in immune cell profiles | Correlations between significant changes in immune cell profiles and biomarkers, and their relation to any significant differences in clinical outcomes | 12 months | |
Secondary | Changes in biomarkers | Correlations between significant changes in biomarkers and their relation to any significant differences in clinical outcomes | 12 months | |
Secondary | Number of patients who experience rejection | Number of patients who experience acute cellular, antibody-mediated, hemodynamic compromise, and any-treated rejection within first 12 months after transplantation/ | 12 months | |
Secondary | Number of episodes per patient | Number of acute cellular, antibody-mediated, hemodynamic compromise and any-treated rejection episodes per patient within the first 12 months post-transplantation | 12 months | |
Secondary | First rejection by ISHLT biopsy grading scale | First acute cellular, antibody-mediated, hemodynamic compromise, and any-treated rejection by the ISHLT biopsy grading scale in the first 12 months post-transplantation | 12 months | |
Secondary | Time to first rejection | Time to first acute cellular, antibody-mediated, hemodynamic compromise, and any-treated rejection within the first 12 months | 12 months | |
Secondary | Incidence of primary graft dysfunction (PGD) | The incidence of Primary Graft Dysfunction(PGD) in the first 24 hours post-transplant | first 24 hours post-transplant | |
Secondary | Patient and graft survival | Patient and graft survival at 12 months post-transplantation | 12 months | |
Secondary | Types of patients with fatal infectious complications | The types of patients with fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation | 12 months | |
Secondary | Number of patients with fatal infectious complications | The number of patients with fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation | 12 months | |
Secondary | Types of patients with non-fatal infectious complications | Types of patients with non-fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation | 12 months | |
Secondary | Number of patients with non-fatal infectious complications | Number of patients with non-fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation | 12 months | |
Secondary | Freedom from development of circulating antibodies | 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 | 12 months | |
Secondary | Change in coronary maximal intimal thickness | Change in coronary maximal intimal thickness at matched sites by intravascular ultrasound at 12 months | 12 months | |
Secondary | Change in coronary intimal area | Change in coronary intimal area at matched sites by intravascular ultrasound at 12 months | 12 months | |
Secondary | Change in coronary intimal volume | Change in coronary intimal volume at matched sites by intravascular ultrasound at 12 months | 12 months | |
Secondary | Change in coronary vessel area | Change in coronary vessel area at matched sites by intravascular ultrasound at 12 months | 12 months | |
Secondary | Change in coronary intimal index | Change in coronary intimal index at matched sites by intravascular ultrasound at 12 months | 12 months | |
Secondary | Change in coronary percent atheroma volume | Change in coronary percent atheroma volume at matched sites by intravascular ultrasound at 12 months | 12 months | |
Secondary | Maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and dose of corticosteroids | Maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and cumulative dose of corticosteroids at 12 months post-transplantation | 12 months | |
Secondary | Number of hospital days per patient | 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 | 3 months, 6 months, 12 months | |
Secondary | Number of patients requiring hospitalization | Number of patients requiring hospitalization by 3 months, by 6 months, or by 1 year post-transplantation | 3 months, 6 months, 12 months | |
Secondary | Death/Re-transplant | To describe between treatment groups the incidence of the composite primary endpoint of death/re-transplant at 12 months post-transplantation | 12 months | |
Secondary | Hemodynamic compromise rejection | 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 | 12 months | |
Secondary | Graft dysfunction | 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 | 12 months | |
Secondary | Cellular rejection | To describe between treatment groups the incidence of the composite primary endpoint of biopsy proven cellular rejection =2R at 12 months post-transplantation | 12 months | |
Secondary | Antibody mediated rejected | To describe between treatment groups the incidence of the composite primary endpoint of biopsy proven antibody mediated rejection =AMR1 at 12 months post-transplantation | 12 months | |
Secondary | Cardiac Allograft Vasculopathy (CAV) | 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) | 12 months | |
Secondary | Any treated rejection | To describe between treatment groups any treated rejection at 12 months | 12 months |
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