Clinical trial NCT00148252: Lowering Total Immunosuppressive Load in Renal Transplant Recipients More Than 12 Months Posttransplant
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®)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Renal Transplantation
Keywords: Calcineurin
reduction
immunosuppression
cyclosporine A
mycophenolate mofetil
Lead sponsor: University of Oslo School of Pharmacy
Sponsor class: OTHER
First posted: 2005-09-07
Enrollment: 298
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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

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 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.

Primary outcomes:
measure: 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 outcomes:
measure: Graft and patient survival at 12 months and 5 years posttransplant.
measure: Proportion of patients with biopsy-proven acute rejection or acute rejection (biopsy proven + presumptive) episodes within 12 months.
measure: Incidence of HB, WBC, platelet abnormal values requiring clinical intervention within 12 months.
measure: Incidence of need for additional immunosuppressive therapy at 12 months.
measure: Absolute difference in renal function between treatment groups at 12 months, evaluated by Nankivell's formula (B).
measure: Renal function (Nankivell's formula B) development over time (3 monthly) between treatment groups within 12 months.
measure: Change in dyslipidemia frequency from drug withdrawal to 12 months.
measure: Change in hypertension frequency from drug withdrawal to 12 months.
measure: Change in glucose tolerance from drug withdrawal to 12 months.
measure: Cumulative incidence of clinical infections resulting in hospitalization within 12 months.
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland sykehus
city: Lillehammer
country: Norway
facility: Lillehammer hospital
city: Nordbyhagen
country: Norway
facility: Akershus Hospital
city: Oslo
country: Norway
facility: Rikshospitalet, Section of Nephrology
city: Oslo
country: Norway
facility: Ullevål hospital
city: Skien
country: Norway
facility: Hospital Telemark
city: Stavanger
country: Norway
facility: Sentralsykehuset i Rogaland
city: Tromsø
country: Norway
facility: Tromsø hospital
city: Trondheim
country: Norway
facility: St. Olavs hospital
Study officials:
affiliation: University of Oslo
name: Anders Åsberg, MSc
role: STUDY_DIRECTOR
References:
citation: Asberg A, Apeland T, Reisaeter AV, Foss A, Leivestad T, Heldal K, Thorud LO, Eriksen BO, Hartmann A; NILS Study Group. Long-term outcomes after cyclosporine or mycophenolate withdrawal in kidney transplantation - results from an aborted trial. Clin Transplant. 2013 Mar-Apr;27(2):E151-6. doi: 10.1111/ctr.12076. Epub 2013 Jan 27.