Clinical trial NCT00157014: Canadian Cardiology de Novo Study: A Comparison Between Tacrolimus- and Cyclosporine- Based Immunoprophylactic Regimens
Official title: Clinical and Laboratory Evaluation of Acute Rejection, Myocyte Growth, Repair, and Oxidative Stress Following de Novo Cardiac Transplant: A Comparison Between Tacrolimus- and Cyclosporine- Based Immunoprophylactic Regimens With MPA TDM
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Diseases
Heart Transplantation
Keywords: Antirejection
Treatment Outcome
Immunosuppression
Treatment Effectiveness
Anti-rejection therapy
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Canada, Inc.
First posted: 2005-09-12
Enrollment: 111
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies
timeFrame: 2 Weeks and 52 Weeks
measure: The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population)
timeFrame: 2 Weeks and 52 Weeks
Secondary outcomes:
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: MCP-1
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: s-ICAM
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: E-selectin
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Homocysteine
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: hsCRP
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: F2 Isoprostanes
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: T-bars
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Nitrotyrosine
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: GSH/GSSG
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: BNP
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Troponin T
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Osteopontin
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Fibrinogen
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-6
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-18
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Cystatin-C
timeFrame: Pre-Transplant and 52 Weeks
measure: Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria
timeFrame: 52 Weeks
measure: Time to First Acute Rejection Episode Following de Novo Cardiac Transplant
timeFrame: 52 Weeks
measure: Number of Patients Requiring Antilymphocyte Antibodies or Steroids for Treatment of Severe Acute Rejection
timeFrame: 52 Weeks
measure: Number of Cardiac Rejection Episodes Requiring Treatment
timeFrame: 52 Weeks
measure: Mean Cases of Acute Rejection (MCAR) Per Patient
timeFrame: 52 Weeks
measure: Number of Patients With Successful Steroid Taper or Withdrawal at Weeks 26 and 52
timeFrame: 26 Weeks and 52 Weeks
measure: Number of Patients With Treatment Failure and Crossover for Treatment Failure
timeFrame: 52 Weeks
measure: Changes in Circulating Markers of Inflammation and Oxidation: F2 Isoprostanes (Pediatric Population)
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation and Oxidation: Nitrotyrosine (Pediatric Population)
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation and Oxidation: hsCRP (Pediatric Population)
timeFrame: Pre-Transplant and 52 Weeks
measure: Changes in Circulating Markers of Inflammation and Oxidation: Cystatin-C (Pediatric Population)
timeFrame: Pre-Transplant and 52 Weeks
measure: Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria (Pediatric Population)
timeFrame: 52 Weeks
measure: Time to First Acute Rejection Episode Following de Novo Cardiac Transplant (Pediatric Population)
timeFrame: 52 Weeks
measure: Number of Patients Requiring Antilymphocyte Antibodies or Steroids for Treatment of Severe Acute Rejection (Pediatric Population)
timeFrame: 52 Weeks
measure: Number of Cardiac Rejection Episodes Requiring Treatment (Pediatric Population)
timeFrame: 52 Weeks
measure: Mean Cases of Acute Rejection (MCAR) Per Patient (Pediatric Population)
timeFrame: 52 Weeks
measure: Number of Patients With Successful Steroid Taper or Withdrawal at Weeks 26 and 52 (Pediatric Population)
timeFrame: 26 Weeks and 52 Weeks
measure: Number of Patients With Treatment Failure and Crossover for Treatment Failure (Pediatric Population)
timeFrame: 52 Weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Halifax
country: Canada
state: Nova Scotia
city: London
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Sainte-Foy
country: Canada
state: Quebec
Study officials:
affiliation: Astellas Pharma Canada, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: