A Study of CellCept (Mycophenolate Mofetil) in Combination Therapy in Heart Transplant Patients.

Study Overview
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Brief Summary
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This study will investigate the efficacy and safety of CellCept (1.5-2g/day po), in combination with a standard care regimen of cyclosporine A (trough level 150-200ng/mL) and steroids, in patients receiving a heart transplant. The anticipated time on study treatment is 24 weeks.

Official Title
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An Open Label Study to Evaluate the Effect of CellCept in Combination With Cyclosporine A and Steroids on Renal Function and the Prevention of Acute Rejection in Heart Transplant Patients.

Conditions
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Heart Transplantation

Intervention / Treatment
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* Drug: mycophenolate mofetil (MMF)
* Drug: cyclosporine A (CsA)
* Drug: corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; patients receiving their first heart transplant (single organ transplant). Exclusion Criteria: patients with a positive donor-specific cross-match at the time of transplantation; patients with any antibody-treated acute rejection; known contraindications to treatment with sirolimus; history of malignancy, other than excised non-melanoma skin cancer which has not recurred for 2 years.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MMF, CsA, Corticosteroids<br>Participants received mycophenolate mofetil (MMF) 1.0 grams (g), orally (PO), twice daily (BID) from within 24 hours of transplantation through Week 24. Participants also received an initial loading dose of cyclosporine A (CsA) 4 to 6 milligrams per kilogram (mg/kg) within 48 hours of transplantation, adjusted thereafter to a blood trough concentration of 150 to 300 nanograms per milliliter (ng/mL) through Week 24. Participants also received corticosteroids as per the practice of each participating center. | Drug: mycophenolate mofetil (MMF)<br>* 1.0 g PO BID<br>* Other names: CellCept;Drug: cyclosporine A (CsA)<br>* Initial loading dose of 4 to 6 mg/kg within 48 hours of transplantation, adjusted thereafter to a blood trough concentration of 150 to 300 ng/mL<br>Drug: corticosteroids<br>* As per the practice of each participating center<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Biopsy Proven Acute Rejection (BPAR) by Week | Percentage of participants with BPAR of greater than or equal to (≥) International Society of Heart and Lung Transplant (ISHLT) Grade III. The ISHLT graded symptoms on a scale of Grade 0 through VI. Grade 0 equals (=) no rejection. Grade IA = regional (perivascular or interstitial) infiltration and no necrosis, and grade IB = dissemination but little infiltration and no necrosis. Grade II = 1 focus of invasive infiltration with or without (+/-) associated cardiomyocyte necrosis. Grade IIIA = 2 or more foci of invasive infiltration +/- associated cardiomyocyte necrosis, and grade IIIB = diffuse inflammatory pathological changes associated with cardiomyocyte necrosis. Grade IV = diffuse, infiltrative multi-foci +/- edema; +/- hemorrhage; and +/-vasculitis. | Day 1, Weeks 1, 2, 4, 8, 12, 16, 20 and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Graft Loss Within 24 Weeks of Transplantation |  | Day 1, Weeks 1, 2, 4, 8, 12, 16, 20 and 24 | 
| Percentage of Participants Requiring Use of Additional Immunosuppressants Not Specified in the Protocol Within 24 Weeks of Transplantation |  | Day 1, Weeks 1, 2, 4, 8, 12, 16, 20 and 24 | 
| Percentage of Participants Discontinuing Immunosuppressants (MMF) for More Than 14 Consecutive Days or 30 Cumulative Days Within 24 Weeks of Transplantation |  | Day 1, Weeks 1, 2, 4, 8, 12, 16, 20 and 24 | 
| Percentage of Participants Lost To Follow Up Within 24 Weeks of Transplantation |  | Day 1, Weeks 1, 2, 4, 8, 12, 16, 20 and 24 | 
| Percentage of Participants With Normal Serum Creatinine and Blood Urea Nitrogen (BUN) Values At Baseline (BL) And During Treatment |  | Day 1, Weeks 1, 2, 4, 8, 12, 16, 20 and 24 | 
| Percentage of Participants With Normal Serum Creatinine and BUN Values at Baseline and Abnormal Values During Treatment |  | Day 1, Weeks 1, 2, 4, 8, 12, 16, 20 and 24 | 
| Percentage of Participants With Abnormal Serum Creatinine and BUN Values at Baseline and Normal Values During Treatment |  | Day 1, Weeks 1, 2, 4, 8, 12, 16, 20 and 24 | 
| Percentage of Participants With Abnormal Serum Creatinine and BUN Values at Baseline and During Treatment |  | Day 1, Weeks 1, 2, 4, 8, 12, 16, 20 and 24 |