Scandinavian Heart Transplant de Novo Study With Early Calcineurin Inhibitor (CNI) Avoidance (SCHEDULE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01266148
First received: August 9, 2010
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

The study population will consist of a representative group 100 de novo heart transplant patients who fulfills the requirements of entering period 2 of the study (patients will continue into period 2 of the study after the completion of period 1 (7-11 weeks after transplantation -TX-), The patients will be randomized at transplantation to receive a standard immunosuppressive protocol of cyclosporine, mycophenolate mofetil (MMF) and corticosteroids (CS)- Group A, or a combination of reduced dose cyclosporine, low dose everolimus, reduced dose MMF and CS- Group B. After 7-11 weeks patients fulfilling the inclusion/exclusion criteria for period 2 will continue in the study for a total of 12 months. In Group A patients will continue with unchanged medication. In Group B cyclosporine will be abruptly withdrawn and the everolimus dose increased. Enrollment will continue until the required sample size (N=100) has entered period 2. An anticipated withdrawal rate in period 1 of about 15% means that about 120 patients need to be randomized. The patients will be recruited from all 5 Scandinavian centers for heart transplantation in Oslo, Gothenburg, Lund, Copenhagen and Aarhus


Condition Intervention Phase
Renal Function
Drug: Everolimus
Drug: Cyclosporine A
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Controlled Randomized Open-label Study Evaluating if Early Initiation of Everolimus (Certican®) and Early Elimination of Cyclosporine (Sandimmun Neoral®) in de Novo Heart Transplant Recipients Can Improve Long-term Renal Function and Slow Down the Progression of Chronic Allograft Vasculopathy (CAV)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • measured glomerular filtration rate (GFR) [ Time Frame: Prior to Day 5 ] [ Designated as safety issue: No ]
    Beginning of study, Prior to transplantation

  • measured glomerular filtration rate (GFR) [ Time Frame: Week 7 ] [ Designated as safety issue: No ]
  • measured glomerular filtration rate (GFR) [ Time Frame: Month 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression of chronic allograft vasculopathy assessed by intravascular ultrasound [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    At Month 12

  • Biopsy proven rejections [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    The occurrence of a biopsy-proven acute rejection is diagnosed from per-protocol biopsies or from biopsies performed for suspected rejection episodes

  • Quality of Life assessments [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    At Month 12

  • Renal function, serum creatinine and creatinine clearance; rate of patients who withdraw prematurely from medication or in whom medication had to be converted to another immunosuppressive regimen due to abnormal lab results, adverse events, or toxicity. [ Time Frame: Up to Month 12 ] [ Designated as safety issue: Yes ]

    Safety parameter are renal function, measurement of serum creatinine and calculated creatinine clearance.

    Tolerability is measured by percentage of patients requiring dose reduction or discontinuation of study drug.

    Safety assessments will consist of monitoring and recording all infections, any malignancies, AEs and SAEs, the regular monitoring of hematology, blood chemistry, and regular measurement of vital signs.


  • Progression of chronic allograft vasculopathy assessed by intravascular ultrasound [ Time Frame: Week 7 ] [ Designated as safety issue: No ]
    At Week 7

  • Quality of Life assessments [ Time Frame: Prior to transplantation ] [ Designated as safety issue: No ]
    Beginning of study

  • Biopsy proven rejections [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    The occurrence of a biopsy-proven acute rejection is diagnosed from per-protocol biopsies or from biopsies performed for suspected rejection episodes

  • Biopsy proven rejections [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    The occurrence of a biopsy-proven acute rejection is diagnosed from per-protocol biopsies or from biopsies performed for suspected rejection episodes

  • Biopsy proven rejections [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    The occurrence of a biopsy-proven acute rejection is diagnosed from per-protocol biopsies or from biopsies performed for suspected rejection episodes

  • Biopsy proven rejections [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    The occurrence of a biopsy-proven acute rejection is diagnosed from per-protocol biopsies or from biopsies performed for suspected rejection episodes

  • Biopsy proven rejections [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
    The occurrence of a biopsy-proven acute rejection is diagnosed from per-protocol biopsies or from biopsies performed for suspected rejection episodes

  • Biopsy proven rejections [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    The occurrence of a biopsy-proven acute rejection is diagnosed from per-protocol biopsies or from biopsies performed for suspected rejection episodes


Estimated Enrollment: 100
Study Start Date: November 2009
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard CsA treatment
Control (Standard cyclosporine treatment)
Drug: Cyclosporine A
CycloA
Experimental: Everolimus
Everolimus
Drug: Everolimus
Everolimus 1.5 mg tablet, b.i.d.
Other Names:
  • Certican
  • Zortress

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female cardiac recipients 18-70 years of age undergoing primary heart transplantation. The graft must be functional at the time of randomization.
  2. Patient willing and capable of giving written informed consent for study participation and anticipated to be able to participate in the study for 12 months
  3. Patients received induction therapy with ATG (Thymoglobulin)

Exclusion Criteria:

  1. Recipient of multi-organ transplants or previously transplanted organs
  2. Patients with donor greater than 70 years
  3. Donor heart cold ischemic time > 6 hours.
  4. Patients who are recipients of ABO incompatible transplants
  5. Patients with platelet count < 50,000/mm3 at the evaluation before transplantation
  6. Patient who have received an unlicensed drug or therapy within one month prior to study entry or if such therapy is to be instituted post-transplantation
  7. Patient with a known hypersensitivity to cyclosporine
  8. Patient with a current severe systemic infection
  9. Patient unable to participate in the study for the full 12-month period
  10. Presence of severe hypercholesterolemia (≥ 350 mg/dL; ≥ 9 mmol/L) or hypertriglyceridemia (≥ 750 mg/dL; ≥ 8.5 mmol/L)
  11. Patients with any past (within the past 5 years) or present malignancy (other than excised basal cell carcinoma)
  12. Females capable of becoming pregnant must have a negative pregnancy test prior to randomization and are required to practice a medically approved method of birth control for the duration of the study and a period of 8 weeks following discontinuation of study medication, even where there has been a history of infertility.
  13. Patients with HIV, hepatitis B or C.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01266148

Locations
Denmark
Skejby University Hospital
Aarhus, Denmark
University Hospital Rigshospitalet
Copenhagen, Denmark
Norway
Oslo University Hospital Rikshospitalet
Oslo, Norway
Sweden
Sahlgrenska University Hospital
Gothenburg, Sweden
Linköping University Hospital
Linköping, Sweden
Lund University Hospital
Lund, Sweden
Sponsors and Collaborators
Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01266148     History of Changes
Other Study ID Numbers: CRAD001ANO02
Study First Received: August 9, 2010
Last Updated: March 6, 2014
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by Novartis:
CNI withdrawal
everolimus
de novo heart transplantation
Study impact of early everolimus treatment and early CNI withdrawal on renal function

Additional relevant MeSH terms:
Cyclosporins
Cyclosporine
Everolimus
Sirolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 17, 2014