The Effect and Safety Profile of Thymoglobulin® in Primary Cardiac Transplant Recipients

Cedars-Sinai Medical Center

Status and phase: Invitation-only; Phase 2

Conditions: Heart Transplantation

Treatments: Drug: Sirolimus; Drug: Corticosteroids; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Drug: Thymoglobulin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03292861

ATG Pilot Study

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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60 participants in 2 patient groups

Thymoglobulin®

Active Comparator group

Description:

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

Treatment:

Drug: Thymoglobulin

Drug: Tacrolimus

Drug: Mycophenolate Mofetil

Drug: Corticosteroids

Drug: Sirolimus

No induction therapy

No Intervention group

Description:

Patients qualifying for the study will be randomized before the transplantation surgery in a 1:1 ratio to either Thymoglobulin® or no treatment.