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

NCT00157014 | Completed Phase 3 Results DMC

• 1 other identifier: FKC-009
• Study Type: interventional
• Target: 111
• Locations: 2 countries
• Sites: 13

Brief Summary

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

Conditions

Heart Diseases; Heart Transplantation

Keywords

Antirejection; Treatment Outcome; Immunosuppression; Treatment Effectiveness; Anti-rejection therapy

Outcome Measures

Primary Outcomes (2)

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

  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 Weeks and 52 Weeks

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

  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.

  2 Weeks and 52 Weeks

Secondary Outcomes (34)

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

  Pre-Transplant and 52 Weeks

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

  Pre-Transplant and 52 Weeks

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

  Pre-Transplant and 52 Weeks

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

  Pre-Transplant and 52 Weeks

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

  Pre-Transplant and 52 Weeks

Study Arms (4)

Tacrolimus - Adult

EXPERIMENTAL

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

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

Cyclosporine - Adult

ACTIVE COMPARATOR

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

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

Tacrolimus - Pediatric

EXPERIMENTAL

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

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

Cyclosporine - Pediatric

ACTIVE COMPARATOR

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

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

Interventions

Tacrolimus DRUG

Oral

Also known as: Prograf, FK506

Tacrolimus - Adult; Tacrolimus - Pediatric

Cyclosporine DRUG

Oral

Cyclosporine - Adult; Cyclosporine - Pediatric

Mycophenolate mofetil DRUG

Intravenous and Oral

Also known as: CellCept

Cyclosporine - Adult; Cyclosporine - Pediatric; Tacrolimus - Adult; Tacrolimus - Pediatric

Methylprednisolone DRUG

Intravenous

Cyclosporine - Adult; Cyclosporine - Pediatric; Tacrolimus - Adult; Tacrolimus - Pediatric

Prednisone DRUG

Oral

Cyclosporine - Adult; Cyclosporine - Pediatric; Tacrolimus - Adult; Tacrolimus - Pediatric

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Inc: lead
• Astellas Pharma Canada, Inc.: collaborator

Study Sites (13)

Unknown Facility

Los Angeles, California, 90095, United States

Location

Unknown Facility

Calgary, Alberta, T2N 2T9, Canada

Location

Unknown Facility

Edmonton, Alberta, T6G 2B7, Canada

Location

Unknown Facility

Edmonton, Alberta, T6G 2E1, Canada

Location

Unknown Facility

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Unknown Facility

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Unknown Facility

London, Ontario, N6A 5A5, Canada

Location

Unknown Facility

Ottawa, Ontario, K1Y 4W7, Canada

Location

Unknown Facility

Toronto, Ontario, M5G 1X8, Canada

Location

Unknown Facility

Toronto, Ontario, M5G 2N2, Canada

Location

Unknown Facility

Montreal, Quebec, H1T 1C8, Canada

Location

Unknown Facility

Montreal, Quebec, H3A 1A1, Canada

Location

Unknown Facility

Sainte-Foy, Quebec, G1V 4G5, Canada

Location

Related Links

• Link to Prescribing Information

MeSH Terms

Conditions

Heart Diseases

Interventions

Tacrolimus; Cyclosporine; Mycophenolic Acid; Methylprednisolone; Prednisone

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols

Limitations and Caveats

Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.

Results Point of Contact

• Title: Associate Director, Scientific Affairs
• Organization: Astellas Pharma Canada, Inc

clinicaltrials@us.astellas.com

Study Officials

• Medical Monitor

  Astellas Pharma Canada, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: May 10, 2004
• Primary Completion: July 18, 2008
• Study Completion: July 18, 2008
• Last Updated: June 5, 2017
• Results First Posted: February 21, 2011

Record last verified: 2017-04

Locations

CA (12); US (1)