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Lowering Total Immunosuppressive Load in Renal Transplant Recipients More Than 12 Months Posttransplant

This study has been terminated.
(To high rejection rate in CsA withdrawal arm)
Sponsor:
Information provided by:
University of Oslo School of Pharmacy
ClinicalTrials.gov Identifier:
NCT00148252
First received: September 6, 2005
Last updated: June 6, 2012
Last verified: June 2012
History of Changes
  Purpose

To compare the change in renal function between CsA or MMF withdrawal from before to 12 months after drug withdrawal in renal transplant recipients on triple immunosuppressive therapy


Condition Intervention Phase
Renal Transplantation
 Drug: Mycophenolate mofetil withdrawal
Drug: Cyclosporione A withdrawal
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Lowering Total Immunosuppressive Load in Renal Transplant Recipients More Than 12 Months Posttransplant - Randomised Withdrawal of Mycophenolate Mofetil (CellCept®) or Cyclosporine A (Sandimmun Neoral®)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Oslo School of Pharmacy:

Primary Outcome Measures:
  • The primary efficacy endpoint is the absolute change in renal function from inclusion to 12 months post drug withdrawal, evaluated as GFR estimated from Nankivell's formula B and normalised for 1.73 m2 body-surface.

Secondary Outcome Measures:
  • Graft and patient survival at 12 months and 5 years posttransplant.
  • Proportion of patients with biopsy-proven acute rejection or acute rejection (biopsy proven + presumptive) episodes within 12 months.
  • Incidence of HB, WBC, platelet abnormal values requiring clinical intervention within 12 months.
  • Incidence of need for additional immunosuppressive therapy at 12 months.
  • Absolute difference in renal function between treatment groups at 12 months, evaluated by Nankivell`s formula (B).
  • Renal function (Nankivell`s formula B) development over time (3 monthly) between treatment groups within 12 months.
  • Change in dyslipidemia frequency from drug withdrawal to 12 months.
  • Change in hypertension frequency from drug withdrawal to 12 months.
  • Change in glucose tolerance from drug withdrawal to 12 months.
  • Cumulative incidence of clinical infections resulting in hospitalization within 12 months.

Estimated Enrollment: 298
Study Start Date: February 2003
Study Completion Date: February 2007
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Detailed Description:

To compare the change in renal function between CsA or MMF withdrawal from before to 12 months after drug withdrawal in renal transplant recipients on triple immunosuppressive therapy.

Secondly to examine safety following withdrawal of CsA or MMF, respectively, by the following parameters:

  • Biopsy verified acute rejection episodes, time to first rejection and number of steroid resistant rejection episodes within 12 months.
  • Hematology (Hb, WBC, platelets) abnormalities within 12 months.
  • Graft and patient survival at 12 months and 5 years. Absolute difference in renal function between withdrawal groups at 12 months. Three monthly changes in renal function from drug withdrawal to 12 months. Change in dyslipidemia frequency from drug withdrawal to 12 months. Change in hypertension frequency from drug withdrawal to 12 months. Change in glucose tolerance from drug withdrawal to 12 months. Cumulative incidence of clinical infections resulting in hospitalization within 12 months.

Sub protocols will also examine the following aspects:

Cardiovascular: Homocysteine. Lipid peroxidation. Microvascular function and vasoactive parameters Quality of life (QoL): ESRD SCL-TM, SF-36 (short version) and EQ-5D (GI-checklist extended) questionnaires will be used.

Pharmacoeconomical evaluation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Patients of either gender above 18 years of age at time of randomisation. 2. More than twelve months posttransplant. 3. Treated with an immunosuppressive protocol consisting of CsA, MMF and steroid from the time of discharge from the transplant clinic (e.g. 3 months posttransplant).

    4. Kidney (only) transplant recipients with stable renal function (S-creatinine < 300 umol/L and an average increase in S-creatinine < 20% the last 6 months prior to inclusion) and without treated clinically and/or biopsy proven acute rejection episodes the last 6 months prior to inclusion.

    5. No previous steroid resistant acute rejections (e.g. treated with ATG/OKT3). 6. Not more than two steroid sensitive acute rejections posttransplant. 7. Signed informed consent.

Exclusion Criteria:

- 1. PRA positivity > 20%. 2. Concomitant therapy with other investigational drugs or prohibited medication specified in the protocol.

3. Life expectancy less than one year. 4. Acute illness or acute fungal, bacterial or viral infection at screening. 5. Unable and/or unlikely to follow the study protocol.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00148252

Locations
Norway
Haukeland sykehus
Bergen, Norway, 5021
Lillehammer hospital
Lillehammer, Norway, 2609
Akershus Hospital
Nordbyhagen, Norway, 1474
Ullevål hospital
Oslo, Norway, 0450
Rikshospitalet, Section of Nephrology
Oslo, Norway, 0027
Hospital Telemark
Skien, Norway, 3710
Sentralsykehuset i Rogaland
Stavanger, Norway, 4068
Tromsø hospital
Tromsø, Norway, 9038
St. Olavs hospital
Trondheim, Norway, 7030
Sponsors and Collaborators
University of Oslo School of Pharmacy
Investigators
Study Director: Anders Åsberg, MSc University of Oslo
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00148252     History of Changes
Other Study ID Numbers: NILS 02-08144
Study First Received: September 6, 2005
Last Updated: June 6, 2012
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by University of Oslo School of Pharmacy:
Calcineurin
reduction
immunosuppression
cyclosporine A
mycophenolate mofetil

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

ClinicalTrials.gov processed this record on May 22, 2013