A Study to Evaluate the Efficacy and Safety of Zenapax in Combination With CellCept, Cyclosporine, and Corticosteroids in Patients Undergoing Cardiac Transplantation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00048165
First received: October 24, 2002
Last updated: March 21, 2016
Last verified: March 2016
  Purpose
The purpose of the study is to compare the number of randomized participants in each treatment group who experience an acute rejection episode in the first 6 months after undergoing cardiac transplantation.

Condition Intervention Phase
Heart Transplantation
Drug: Daclizumab
Drug: Methylprednisolone
Drug: Mycophenolate mofetil
Drug: Placebo
Drug: cyclosporine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo -Controlled, Randomized Study to Assess the Efficacy and Safety of Zenapax in Combination With CellCept, Cyclosporine, and Corticosteroids in Patients Undergoing Cardiac Transplatation.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Number of participants who developed acute rejection episode within the first 6 months following transplantation [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants with marked laboratory abnormalities [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Number of participants who developed acute rejection episode within the 12 months following transplantation [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Number of acute rejection episodes per participant within the first 6 months and within the first 12 months post-transplantation [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Participant and graft survival at 6 months, at 12 months, and at 3 years post transplantation [ Time Frame: At 6 months, 12 months, and 3 years ] [ Designated as safety issue: No ]
  • Participants With Worst International Society of Heart and Lung Transplant (ISHLT) biopsy grade in the first 6 months and within the first 12 months post-transplantation [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Time to first acute rejection episode within the first 6 months and within the first 12 months [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Use of Monomunab CD3, Orthoclone (OKT3) or Antithymocyte globulin (ATGAM) in the first 6 months post-transplantation [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • Maintenance doses of CellCept and cyclosporine, and cumulative dose of corticosteroids at 6 and 12 months post-transplantation [ Time Frame: At 6 and 12 months ] [ Designated as safety issue: No ]
  • Change from baseline for lipid profile [ Time Frame: Baseline (Day 1), 3 months, and 6 months ] [ Designated as safety issue: No ]
  • Number of participants with adverse events, malignancies, opportunistic infections, and premature withdrawal due to adverse events [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

Enrollment: 434
Study Start Date: August 1999
Study Completion Date: August 2002
Primary Completion Date: August 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daclizumab
Daclizumab will be administered as a intravenous dose of 1 milligrams per kilogram [mg/kg] on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg, and 500-1000 mg IV methylprednisolone peri operative switch to oral at 0.5-1 mg/kg/day followed by tapering.
Drug: Daclizumab
Daclizumab will be administered as 1 mg/kg IV within 12 hours post-op (Day 1), and Days 8, 22, 36 and 50.
Other Name: Zenapax
Drug: Methylprednisolone
Methylprednisolone will be administered as 500-1000 mg IV and peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering till 0.0-0.15 mg/kg/day (up to 365 days).
Drug: Mycophenolate mofetil
Mycophenolate mofetil will be administered as 1.5 grams bid begun post-op, either IV or orally as required up to 365 days.
Drug: cyclosporine
Cyclosporine will be administered as 1-4 mg/kg IV or 2-6 mg/kg orally up to 365 days.
Placebo Comparator: Placebo
Matching placebo will be administered on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg orally, and 500-1000 mg IV methylprednisolone peri-op switch to oral at 0.5-1 mg/kg/day followed by tapering.
Drug: Methylprednisolone
Methylprednisolone will be administered as 500-1000 mg IV and peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering till 0.0-0.15 mg/kg/day (up to 365 days).
Drug: Mycophenolate mofetil
Mycophenolate mofetil will be administered as 1.5 grams bid begun post-op, either IV or orally as required up to 365 days.
Drug: Placebo
Matching placebo will be administered on Days 1, 8, 22, 36, and 50.
Drug: cyclosporine
Cyclosporine will be administered as 1-4 mg/kg IV or 2-6 mg/kg orally up to 365 days.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must be undergoing their first cardiac allograft transplant
  • Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to transplantation
  • Women of childbearing potential must use two reliable forms of contraception simultaneously. Effective contraception must be used before beginning study drug therapy, and for 4 months following discontinuation of study drug therapy
  • Participants and/or their guardians must be willing and be capable of understanding risks and comply with the purpose of the study

Exclusion Criteria:

  • Previous organ transplants
  • Participants receiving multiple organs
  • Participants requiring ventricular assist device (VAD) upon completion of transplantation surgery
  • Women lactating, pregnant or of childbearing potential not using, or who are unwilling to use two reliable forms of contraception simultaneously during the study
  • History of a psychological illness or condition which would interfere with the participant's ability to understand the requirements of the study
  • White blood count =<2500/mm^3, platelets =<50,000/mm^3 or hemoglobin =<6 g/dL
  • HIV-1, the presence of positive HBsAg, or chronic active hepatitis C
  • Active peptic ulcer disease
  • Severe diarrhea or other gastrointestinal disorders which might interfere with their ability to absorb oral medication
  • Malignancies within the past 5 years, excluding skin carcinoma that have been adequately treated
  • Participants who have received within the past 30 days or require concomitant treatment with other investigational drugs or immunosuppressive medications that are prohibited for this study
  • Inability to start microemulsion form of cyclosporine within 72 hours
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00048165

  Show 32 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00048165     History of Changes
Other Study ID Numbers: NR15880 
Study First Received: October 24, 2002
Last Updated: March 21, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cyclosporine
Cyclosporins
Daclizumab
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Mycophenolate mofetil
Mycophenolic Acid
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents
Dermatologic Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on May 04, 2016