Randomized Study to Reduce Calcineurininhibitor Toxicity in Pediatric and Adolescent Kidney Transplant Recipients (Recaltox)

This study has been terminated.
(Recruitment goals were not achieved. Extension of the trial concept had to be abjected due to methodological reasons.)
Sponsor:
Information provided by:
University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier:
NCT00663455
First received: April 21, 2008
Last updated: November 9, 2010
Last verified: November 2010

April 21, 2008
November 9, 2010
December 2008
December 2012   (final data collection date for primary outcome measure)
Mean decline per month in glomerular filtration rate (calculated acc. to Schwartz' formula) during the clinical trial - comparison between the two study arms (CSA-dose reduction group and group with constant CSA-dosing) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00663455 on ClinicalTrials.gov Archive Site
  • Evaluation of the NFAT-regulated gene expression (nuclear factor of activated t-cells) of intracellular cytokines [Interleukin-2, TNF-alpha, Interferon-gamma and GMCSF) by quantitative PCR as measurement of CSA activity [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Health-related Quality of life evaluation using validated questionnaires (TACQoL) to determine differences between the two study arms [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Evaluation of the NFAT-regulated gene expression (nuclear factor of activated t-cells) of intracellular cytokines [Interleucin-2, TNF-alpha, Interferon-gamma and GMCSF)by quantitative PCR as measurement of CSA activity [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Health-related Quality of life evaluation using validated questionnaires (TACQoL)to determine differences between the two nstudy arms [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Randomized Study to Reduce Calcineurininhibitor Toxicity in Pediatric and Adolescent Kidney Transplant Recipients
A Multicenter, Randomized, Parallel-group, Trial to Reduce Toxicity of Calcineurininhibitor-therapy in Steroid-free Longterm Immunosuppression in Pediatric and Adolescent Kidney Transplant Recipients

The purpose of this study is to determine if a safe reduction of cyclosporine A in pediatric and adolescent patients with stable renal graft function, reduces signs of calcineurin-inhibitor toxicity.

Chronic transplant nephropathy is one of the major causes of graft loss after renal transplantation. Toxicity of calcineurin-inhibitors is suspected to be one cause for loss of graft function. Therefore reduction of cyclosporine A dosing can result in longer graft survival and better graft function in patients after renal-transplantation. However, reduction of immunosuppression can result in acute rejection episodes, although it is less likely in patients with stable graft function 12 months or longer after successful renal transplantation.

Therefore the aim of this randomized, controlled study in pediatric and adolescent renal transplant recipients, is to compare the impact of reduced cyclosporine A-dosing to standard CSA-dosing on renal graft function. Therapy monitoring in both groups will be performed by obtaining CSA blood levels two hours after intake, as they provide an individual insight in pharmacokinetics in comparison to conventional trough level (C0)-measurements.

Secondary objectives to evaluate are

  1. the evaluation of the health-related Quality of life and psychosocial burden in the two treatment arms.
  2. measurement of the NFAT-regulated gene expression (nuclear factor of activated t-cells) of intracellular cytokines [Interleukin-2, TNF-alpha, Interferon-gamma and GMCSF) by quantitative PCR as measurement of CSA activity.
  3. To obtain new insights by screening for metabolites conjunct with clinic features of nephrotoxicity or graft rejections a metabolomic screening and a targeted analysis (trimethylamine-N-oxide, neopterin and kynurenine/tryptophan ratio) will be performed.
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Kidney Transplant
Drug: Reduction of cyclosporine A (CSA)-dosing
Reduction of CSA-dosing over 4 months. Therapy control by safety parameters (serum creatinine, C2-monitoring, renal biopsy).
  • A
    Reduction of CSA-dosing over 4 months. Therapy control by safety parameters (serum creatinine, C2-monitoring, renal biopsy).
    Intervention: Drug: Reduction of cyclosporine A (CSA)-dosing
  • No Intervention: B
    Standard CSA-dosing without reduction. Therapy control by C2-monitoring.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
50
June 2013
December 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • age at inclusion 3-16 years
  • male or female patients
  • recipient of first or second renal transplant
  • graft age > 24 months
  • last acute rejection episode > 6 months ago
  • Immune suppression comedication Mycophenolatmofetil (MMF) in a dose range of 1200 +/- 200 mg/m² BSA/d within at least 6 months or minimal MPA-AUC ≥ 45 mg x h/l. If MPA-AUC < 45 mg x h/l adjustment of dosage with re-screening in ≥ 4 weeks is possible.
  • Application of CSA in stable dosing within the last 3 months before study inclusion and CSA-C2-level > 500 ng/ml. If CSA-C2-level < 500 ng/ml adjustment of dosage with re-screening in ≥ 4 weeks is possible.
  • steroid-free immunosuppression for at least 6 months before enrollment
  • biopsy of the renal graft without any signs of acute rejection (def. according to BANFF classification), within 3 months before enrollment
  • written informed consent of parents/legal guardians and, if applicable, patient's consent

Exclusion Criteria:

  • glomerular filtration rate < 40 ml/min/1.73 m2 BSA (acc. to Schwartz' formula) at time of enrollment
  • > 2 episodes of acute graft rejection within 12 months prior to enrollment
  • condition after steroid-resistant graft rejection
  • actual participation in another clinical trial
  • Recurrence of primary renal disease in the graft
  • proven infection with EBV and/ or CMV and antiviral therapy within 3 months prior to enrollment
  • proven infection with polyoma virus within 3 months prior to enrolment
  • pregnant or nursing women
  • hemoglobin < 8 g/dl at screening visit
  • non-treated arterial hypertension
  • uncontrolled infectious disease
  • history of malignancy of any organ system, treated or non-treated
Both
3 Years to 16 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00663455
Recaltox-1
Yes
Professor Dr. Jörg Dötsch, MD, Dep. of Pediatrics, University of Erlangen-Nürnberg
University of Erlangen-Nürnberg Medical School
Not Provided
Principal Investigator: Jörg Dötsch, MD Dept. of Pediatric Nephrology, University Hospital Erlangen, Germany
University of Erlangen-Nürnberg Medical School
November 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP