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

NCT ID: NCT03292861

Last Updated: 2024-12-16

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-13
• Study Completion Date: 2025-10-31

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.

Conditions

Heart Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Thymoglobulin

Intervention Type: DRUG

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 8 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 4-8 hours.

Mycophenolate Mofetil

Intervention Type: DRUG

3.0 grams divided bid begun post-transplant, either IV or po as tolerated by patient. Initial dose must be given within 24 hours post-transplant. Dosing will be titrated based on recipient's body size and any adverse side effects

Tacrolimus

Intervention Type: DRUG

Doses of 1-4 mg bid either IV or po will be prescribed to achieve a target trough level of 10-15 ng/mL before post-operative day number 5. Target trough levels are 10-15 ng/mL for post-operative days #1-30, 8-12ng/mL days#31-60 and 5-10 ng/mL thereafter.

Sirolimus

Intervention Type: DRUG

Maintenance doses of sirolimus at 12 months post-transplantation

Corticosteroids

Intervention Type: DRUG

125 mg IV methylprednisolone immediately post-operatively x 3 doses q12hrs, then switching to oral prednisone at 1.0 mg/kg/day po divided into bid doses that are rounded off to the next higher 5 mg increment. For example, a 76 kg person would should be dosed at 38 mg po bid, which rounded off to the next 5 mg increment would be 40 mg po bid. (Equivalent dosing via an alternative route may be used if pos not tolerated or contraindicated). Prednisone will be tapered by 10 mg qd until the dose of 10 mg po bid is reached.

No induction therapy

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Thymoglobulin

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 8 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 4-8 hours.

Intervention Type: DRUG

Mycophenolate Mofetil

3.0 grams divided bid begun post-transplant, either IV or po as tolerated by patient. Initial dose must be given within 24 hours post-transplant. Dosing will be titrated based on recipient's body size and any adverse side effects

Intervention Type: DRUG

Tacrolimus

Doses of 1-4 mg bid either IV or po will be prescribed to achieve a target trough level of 10-15 ng/mL before post-operative day number 5. Target trough levels are 10-15 ng/mL for post-operative days #1-30, 8-12ng/mL days#31-60 and 5-10 ng/mL thereafter.

Intervention Type: DRUG

Sirolimus

Maintenance doses of sirolimus at 12 months post-transplantation

Intervention Type: DRUG

Corticosteroids

125 mg IV methylprednisolone immediately post-operatively x 3 doses q12hrs, then switching to oral prednisone at 1.0 mg/kg/day po divided into bid doses that are rounded off to the next higher 5 mg increment. For example, a 76 kg person would should be dosed at 38 mg po bid, which rounded off to the next 5 mg increment would be 40 mg po bid. (Equivalent dosing via an alternative route may be used if pos not tolerated or contraindicated). Prednisone will be tapered by 10 mg qd until the dose of 10 mg po bid is reached.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Jon Kobashigawa

Director of Advanced Heart Disease Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jon Kobashigawa, MD

Role: PRINCIPAL_INVESTIGATOR

Director

Locations

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

ATG Pilot Study

Identifier Type: -

Identifier Source: org_study_id