Canadian Cardiology de Novo Study: A Comparison Between Tacrolimus- and Cyclosporine- Based Immunoprophylactic Regimens

Astellas

Status and phase: Completed; Phase 3

Conditions: Heart Diseases; Heart Transplantation

Treatments: Drug: Mycophenolate mofetil; Drug: Tacrolimus; Drug: Prednisone; Drug: Cyclosporine; Drug: Methylprednisolone

Study type: Interventional

Funder types: Industry

Identifiers

NCT00157014

FKC-009

Details and patient eligibility

About

The purpose of this study is to assess the safety and efficacy of tacrolimus in de novo heart transplantation.

Full description

Subcellular markers will be assessed in relationship to cellular acute rejection in de novo cardiac transplant recipients receiving either tacrolimus or cyclosporine as their primary immunosuppressant

Two parallel active arms.

Enrollment: 111 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients (or their legal guardians) who are capable of understanding, and who have been fully informed of the purpose of the study and the risks of participation.
• Patients (or their legal guardians) who have signed and dated the Informed Consent form and are willing and able to follow the study protocol.
• Patients who are primary cadaveric heart transplant recipients.
• Males or females from birth.
• Female patients of child-bearing potential who have a current negative pregnancy test and agree to practice effective birth control, as judged by the investigator, while participating in the study. Prepubescent pediatric patients will not require pregnancy testing.
• Patients able to tolerate oral medication and who do not have a gastrointestinal condition likely to affect the absorption kinetics or metabolism of the oral study medications.

Exclusion criteria

• Previous organ transplant recipients.

• Multi-organ transplant recipients.

• Recipients of a heart from a donor with incompatible ABO blood type.

• Patients with significant graft dysfunction and/or significant de novo infection(s) at time of randomization

• Patients with known hypersensitivity to tacrolimus, cyclosporine, mycophenolate mofetil (MMF), daclizumab, prednisone, cremophor, polysorbate 80 and/or polyoxyl 60 hydrogenated castor oil (HCO-60).

• Patients who are pregnant or lactating or planning to become pregnant prior to completion of the study.

• Patients who have consumed an investigational product in the 30 days prior to transplantation or at any time during post-transplantation follow-up.

• Patients receiving cholestyramine or colestipol.

• Patients having any one of the following at enrolment:

  1. History of malignancy, not chart-documented as cured or active malignancy (with exception of eradicable non-metastatic in-situ basal cell or squamous cell carcinoma).
  2. Leukopenia (white cell count < 2500/cu mm).
  3. Anemia (hemoglobin < 80 g/L).
  4. Positive test for hepatitis B surface antigen and/or hepatitis C.
  5. Historical positive test for human immunodeficiency virus (HIV).
  6. Serum creatinine > 230 umol/l.
  7. Continual elevation of AST and/or ALT to >= 3X the upper limit of normal.
  8. Body mass index (weight in kg/height in m2) > 30.

• Undiagnosed diabetes mellitus as determined by 2 hour (2h) oral glucose tolerance test (OGTT) or fasting glucose test or uncontrolled diabetes mellitus at screening. In either case, the patient may be declared as no longer excluded by this criterion upon establishment of control of the diabetes through appropriate medical management.

• Blood glucose >= 11.1 mmol/L at pre-operative assessment.

• Patients having a significant disease, substance dependency, or disability that may prevent adherence to, or understanding of, the protocol and/or the investigator's instructions.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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111 participants in 4 patient groups

Tacrolimus - Adult

Experimental group

Description:

Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant

Treatment:

Drug: Prednisone

Drug: Methylprednisolone

Drug: Mycophenolate mofetil

Drug: Tacrolimus

Cyclosporine - Adult

Active Comparator group

Description:

Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant

Treatment:

Drug: Prednisone

Drug: Methylprednisolone

Drug: Mycophenolate mofetil

Drug: Cyclosporine

Tacrolimus - Pediatric

Experimental group

Description:

Pediatrics: 0.05 - 0.30 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant

Treatment:

Drug: Prednisone

Drug: Methylprednisolone

Drug: Mycophenolate mofetil

Drug: Tacrolimus

Cyclosporine - Pediatric

Active Comparator group

Description:

Pediatrics: 6 - 10 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant

Treatment:

Drug: Prednisone

Drug: Methylprednisolone

Drug: Mycophenolate mofetil

Drug: Cyclosporine