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Enrolling by Invitation

NCT Number: NCT03292861

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

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.

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Key information

Conditions

Heart Transplantation

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Cedars-Sinai Medical Center, Los Angeles, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for Study Entry:

  • Subjects must be undergoing their first allograft transplant
  • Men and non-pregnant women must be 18 to 70 years old
  • 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)
  • 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.
  • Subjects must be willing and capable of understanding the purpose and risks of the study, and must sign a statement of informed consent
  • Subjects with a Creatinine < 2.0 mg/dl at time of transplant

Exclusion criteria

for Study Entry:

  • 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
  • Previous organ transplants
  • Patients receiving multiple organs
  • Patients with a BMI higher than 35
  • Patients with PRA ≥ 25%
  • Patients requiring VAD upon completion of transplantation surgery.
  • HIV-1, HTLV-1, chronic Hepatitis B, or chronic Hepatitis C infection
  • Documented or strong suspicion for pre-operative active infection that has not yet been adequately treated with the recommended course of antimicrobial therapy
  • Presence of any chronic myelosuppressive disease or agent that has resulted in either chronic leucopenia or chronic thrombocytopenia
  • Active peptic ulcer disease and active GI bleeding
  • 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")
  • Patients with a history of AL amyloidosis (TTR amyloids) are permitted

Treatment and study plan

Thymoglobulin

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

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

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

Drug

Maintenance doses of sirolimus at 12 months post-transplantation

Corticosteroids

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.

Primary outcomes

  1. Percentage of Participants With Composite Efficacy Failure at 12 Months

    Time frame: 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 outcomes

  1. Changes in immune cell profiles

    Time frame: 12 months

    Correlations between significant changes in immune cell profiles and biomarkers, and their relation to any significant differences in clinical outcomes

  2. Changes in biomarkers

    Time frame: 12 months

    Correlations between significant changes in biomarkers and their relation to any significant differences in clinical outcomes

  3. Number of patients who experience rejection

    Time frame: 12 months

    Number of patients who experience acute cellular, antibody-mediated, hemodynamic compromise, and any-treated rejection within first 12 months after transplantation/

  4. Number of episodes per patient

    Time frame: 12 months

    Number of acute cellular, antibody-mediated, hemodynamic compromise and any-treated rejection episodes per patient within the first 12 months post-transplantation

  5. First rejection by ISHLT biopsy grading scale

    Time frame: 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

  6. Time to first rejection

    Time frame: 12 months

    Time to first acute cellular, antibody-mediated, hemodynamic compromise, and any-treated rejection within the first 12 months

  7. Incidence of primary graft dysfunction (PGD)

    Time frame: first 24 hours post-transplant

    The incidence of Primary Graft Dysfunction(PGD) in the first 24 hours post-transplant

  8. Patient and graft survival

    Time frame: 12 months

    Patient and graft survival at 12 months post-transplantation

  9. Types of patients with fatal infectious complications

    Time frame: 12 months

    The types of patients with fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation

  10. Number of patients with fatal infectious complications

    Time frame: 12 months

    The number of patients with fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation

  11. Types of patients with non-fatal infectious complications

    Time frame: 12 months

    Types of patients with non-fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation

  12. Number of patients with non-fatal infectious complications

    Time frame: 12 months

    Number of patients with non-fatal infectious complications (especially CMV infection) within the first 12 months post-transplantation

  13. Freedom from development of circulating antibodies

    Time frame: 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

  14. Change in coronary maximal intimal thickness

    Time frame: 12 months

    Change in coronary maximal intimal thickness at matched sites by intravascular ultrasound at 12 months

  15. Change in coronary intimal area

    Time frame: 12 months

    Change in coronary intimal area at matched sites by intravascular ultrasound at 12 months

  16. Change in coronary intimal volume

    Time frame: 12 months

    Change in coronary intimal volume at matched sites by intravascular ultrasound at 12 months

  17. Change in coronary vessel area

    Time frame: 12 months

    Change in coronary vessel area at matched sites by intravascular ultrasound at 12 months

  18. Change in coronary intimal index

    Time frame: 12 months

    Change in coronary intimal index at matched sites by intravascular ultrasound at 12 months

  19. Change in coronary percent atheroma volume

    Time frame: 12 months

    Change in coronary percent atheroma volume at matched sites by intravascular ultrasound at 12 months

  20. Maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and dose of corticosteroids

    Time frame: 12 months

    Maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and cumulative dose of corticosteroids at 12 months post-transplantation

  21. Number of hospital days per patient

    Time frame: 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

  22. Number of patients requiring hospitalization

    Time frame: 3 months, 6 months, 12 months

    Number of patients requiring hospitalization by 3 months, by 6 months, or by 1 year post-transplantation

  23. Death/Re-transplant

    Time frame: 12 months

    To describe between treatment groups the incidence of the composite primary endpoint of death/re-transplant at 12 months post-transplantation

  24. Hemodynamic compromise rejection

    Time frame: 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

  25. Graft dysfunction

    Time frame: 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

  26. Cellular rejection

    Time frame: 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

  27. Antibody mediated rejected

    Time frame: 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

  28. Cardiac Allograft Vasculopathy (CAV)

    Time frame: 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)

  29. Any treated rejection

    Time frame: 12 months

    To describe between treatment groups any treated rejection at 12 months

Sponsors and collaborators

Lead sponsor

Cedars-Sinai Medical Center

Other

Collaborators

  • Genzyme, a Sanofi Company

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2026
Study completion
2026
First posted
Sep 26, 2017
Registry last updated
Jan 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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