Clinical trial NCT03292861: The Effect and Safety Profile of Thymoglobulin® in Primary Cardiac Transplant Recipients
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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Heart Transplantation
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2017-09-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants With Composite Efficacy Failure at 12 Months
timeFrame: 12 Months
Secondary outcomes:
measure: Changes in immune cell profiles
timeFrame: 12 months
measure: Changes in biomarkers
timeFrame: 12 months
measure: Number of patients who experience rejection
timeFrame: 12 months
measure: Number of episodes per patient
timeFrame: 12 months
measure: First rejection by ISHLT biopsy grading scale
timeFrame: 12 months
measure: Time to first rejection
timeFrame: 12 months
measure: Incidence of primary graft dysfunction (PGD)
timeFrame: first 24 hours post-transplant
measure: Patient and graft survival
timeFrame: 12 months
measure: Types of patients with fatal infectious complications
timeFrame: 12 months
measure: Number of patients with fatal infectious complications
timeFrame: 12 months
measure: Types of patients with non-fatal infectious complications
timeFrame: 12 months
measure: Number of patients with non-fatal infectious complications
timeFrame: 12 months
measure: Freedom from development of circulating antibodies
timeFrame: 12 months
measure: Change in coronary maximal intimal thickness
timeFrame: 12 months
measure: Change in coronary intimal area
timeFrame: 12 months
measure: Change in coronary intimal volume
timeFrame: 12 months
measure: Change in coronary vessel area
timeFrame: 12 months
measure: Change in coronary intimal index
timeFrame: 12 months
measure: Change in coronary percent atheroma volume
timeFrame: 12 months
measure: Maintenance doses of mycophenolate mofetil, tacrolimus, sirolimus, and dose of corticosteroids
timeFrame: 12 months
measure: Number of hospital days per patient
timeFrame: 3 months, 6 months, 12 months
measure: Number of patients requiring hospitalization
timeFrame: 3 months, 6 months, 12 months
measure: Death/Re-transplant
timeFrame: 12 months
measure: Hemodynamic compromise rejection
timeFrame: 12 months
measure: Graft dysfunction
timeFrame: 12 months
measure: Cellular rejection
timeFrame: 12 months
measure: Antibody mediated rejected
timeFrame: 12 months
measure: Cardiac Allograft Vasculopathy (CAV)
timeFrame: 12 months
measure: Any treated rejection
timeFrame: 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
affiliation: Director
name: Jon Kobashigawa, MD
role: PRINCIPAL_INVESTIGATOR
References: