Skip to main content
OpenTrials
Completed

NCT Number: NCT00157014

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

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

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Heart Diseases Cardiovascular Diseases Heart Transplantation

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Calgary, Alberta, Canada

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • 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).
  • Leukopenia (white cell count < 2500/cu mm).
  • Anemia (hemoglobin < 80 g/L).
  • Positive test for hepatitis B surface antigen and/or hepatitis C.
  • Historical positive test for human immunodeficiency virus (HIV).
  • Serum creatinine > 230 umol/l.
  • Continual elevation of AST and/or ALT to >= 3X the upper limit of normal.
  • 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.

Treatment and study plan

Tacrolimus

Drug

Oral

Other names: Prograf, FK506

cyclosporine

Drug

Oral

Mycophenolate mofetil

Drug

Intravenous and Oral

Other names: CellCept

methylprednisolone

Drug

Intravenous

Prednisone

Drug

Oral

Primary outcomes

  1. The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies

    Time frame: 2 Weeks and 52 Weeks

    The markers assessed were p-ERK ½ (phosphorylated extracellular signal-regulated kinase), p-JNK (phosphorylated jun N-terminal kinase) and p-p38 MAPK (phosphorylated mitogen-activated protein kinase).

    The data for each biopsy marker were expressed as a ratio of its densitometry / densitometry of glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

    Change is defined as Week 52 assessment- Week 2 assessment.

  2. The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population)

    Time frame: 2 Weeks and 52 Weeks

    The markers assessed were p-ERK ½, p-JNK and p-p38 MAPK.

    The data for each biopsy marker were expressed as a ratio of its densitometry / densitometry of glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

    Change is defined as Week 52 assessment- Week 2 assessment.

Secondary outcomes

  1. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: MCP-1

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

    MCP-1= monocyte chemoattractant protein-1

  2. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: s-ICAM

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

    s-ICAM= soluble-intracellular adhesion molecule

  3. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: E-selectin

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

  4. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Homocysteine

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

  5. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: hsCRP

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

    hsCRP= high-sensitivity C Reactive Protein

  6. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: F2 Isoprostanes

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

  7. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: T-bars

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

    T-bars = thiobarbituric acid reactive substances

  8. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Nitrotyrosine

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

  9. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: GSH/GSSG

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

    GSH/GSSG= ratio of reduced to oxidised glutathione

  10. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: BNP

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

    BNP= Brain Natriuretic Peptide

  11. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Troponin T

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

  12. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Osteopontin

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

  13. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Fibrinogen

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

  14. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-6

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

    IL= Interleukin

  15. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-18

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

  16. Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Cystatin-C

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment.

  17. Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria

    Time frame: 52 Weeks

    Acute rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

    ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

    Patients may report more than one acute rejection.

  18. Time to First Acute Rejection Episode Following de Novo Cardiac Transplant

    Time frame: 52 Weeks

    Acute Rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

    ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

    Time to first acute rejection is defined as: date of onset - date of transplant.

  19. Number of Patients Requiring Antilymphocyte Antibodies or Steroids for Treatment of Severe Acute Rejection

    Time frame: 52 Weeks

    Severe Acute Rejection is defined as rejection with ISHLT Grade 4.

  20. Number of Cardiac Rejection Episodes Requiring Treatment

    Time frame: 52 Weeks

    The number of rejection episodes requiring treatment (medications started/ stopped, non-medication treatment, or both) regardless of biopsy grade or presence of hemodynamic compromise.

  21. Mean Cases of Acute Rejection (MCAR) Per Patient

    Time frame: 52 Weeks

    MCAR represents the average number of acute rejections among all patients in each treatment group. Results were based on rejection episodes with endomyocardial biopsies.

    Acute rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

    ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

  22. Number of Patients With Successful Steroid Taper or Withdrawal at Weeks 26 and 52

    Time frame: 26 Weeks and 52 Weeks

    A successful steroid taper or withdrawal was defined as steroids (prednisone) being discontinued or tapered to the suggested dose level after week 26.

  23. Number of Patients With Treatment Failure and Crossover for Treatment Failure

    Time frame: 52 Weeks

    Treatment failure was defined as death, re-transplantation, withdrawal due to an Adverse Event, or a switch of main immunosuppressant medication, whichever came first.

    Crossover was defined as a switch from originally administered primary immunosuppressant (tacrolimus or cyclosporine) to the alternate primary immunosuppressant.

  24. Changes in Circulating Markers of Inflammation and Oxidation: F2 Isoprostanes (Pediatric Population)

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment

  25. Changes in Circulating Markers of Inflammation and Oxidation: Nitrotyrosine (Pediatric Population)

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment

  26. Changes in Circulating Markers of Inflammation and Oxidation: hsCRP (Pediatric Population)

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment

  27. Changes in Circulating Markers of Inflammation and Oxidation: Cystatin-C (Pediatric Population)

    Time frame: Pre-Transplant and 52 Weeks

    Change is defined as Week 52 assessment - Pre-Transplant assessment

  28. Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria (Pediatric Population)

    Time frame: 52 Weeks

    Acute rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

    ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

    Patients may report more than one rejection episode.

  29. Time to First Acute Rejection Episode Following de Novo Cardiac Transplant (Pediatric Population)

    Time frame: 52 Weeks

    Acute Rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

    ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

    Time to first acute rejection is defined as: date of onset - date of transplant.

  30. Number of Patients Requiring Antilymphocyte Antibodies or Steroids for Treatment of Severe Acute Rejection (Pediatric Population)

    Time frame: 52 Weeks

    Severe Acute Rejection was defined as rejection with ISHLT Grade 4.

  31. Number of Cardiac Rejection Episodes Requiring Treatment (Pediatric Population)

    Time frame: 52 Weeks

    A summary of rejection episodes requiring treatment regardless of biopsy grade or presence of hemodynamic compromise.

  32. Mean Cases of Acute Rejection (MCAR) Per Patient (Pediatric Population)

    Time frame: 52 Weeks

    MCAR represents the average number of acute rejections among all patients in each treatment group. Results were based on rejection episodes with endomyocardial biopsies.

    Acute rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

    ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

  33. Number of Patients With Successful Steroid Taper or Withdrawal at Weeks 26 and 52 (Pediatric Population)

    Time frame: 26 Weeks and 52 Weeks

    A successful steroid taper or withdrawal was defined as steroids (prednisone) being discontinued or tapered to the suggested dose level after week 26.

  34. Number of Patients With Treatment Failure and Crossover for Treatment Failure (Pediatric Population)

    Time frame: 52 Weeks

    Treatment failure was defined as death, re-transplantation, withdrawal due to an Adverse Event, or a switch of main immunosuppressant medication, whichever came first.

    Crossover was defined as a switch from originally administered primary immunosuppressant (tacrolimus or cyclosporine) to the alternate primary immunosuppressant.

Sponsors and collaborators

Lead sponsor

Astellas Pharma Inc

Industry

Collaborators

  • Astellas Pharma Canada, Inc.

Registry information

Official study 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

Important dates

Study start
2004
Primary completion
2008
Study completion
2008
First posted
Sep 12, 2005
Registry last updated
Jun 5, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.