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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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.
• Препарат 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
• Препарат 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.
• Препарат Sirolimus
  Maintenance doses of sirolimus at 12 months post-transplantation
• Препарат 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 1

Первичные конечные точки

• Percentage of Participants With Composite Efficacy Failure at 12 Months [Срок оценки: 12 Months]

Вторичные конечные точки (12)

• Changes in immune cell profiles [Срок оценки: 12 months]
• Changes in biomarkers [Срок оценки: 12 months]
• Number of patients who experience rejection [Срок оценки: 12 months]
• Number of episodes per patient [Срок оценки: 12 months]
• First rejection by ISHLT biopsy grading scale [Срок оценки: 12 months]
• Time to first rejection [Срок оценки: 12 months]
• Incidence of primary graft dysfunction (PGD) [Срок оценки: first 24 hours post-transplant]
• Patient and graft survival [Срок оценки: 12 months]
• Types of patients with fatal infectious complications [Срок оценки: 12 months]
• Number of patients with fatal infectious complications [Срок оценки: 12 months]
• Types of patients with non-fatal infectious complications [Срок оценки: 12 months]
• Number of patients with non-fatal infectious complications [Срок оценки: 12 months]

Критерии участия

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Kaiser Permanente Los Angeles Medical Center — Los Angeles
• Cedars-Sinai Medical Center — Los Angeles

Идентификаторы

NCT: NCT03292861 · ATG Pilot Study

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗