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Trial record 2 of 2 for:    Chronic Kidney Disease in Children Prospective Cohort Study (CKiD)

Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01598987
Recruitment Status : Completed
First Posted : May 15, 2012
Results First Posted : January 24, 2017
Last Update Posted : May 16, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE March 1, 2012
First Posted Date  ICMJE May 15, 2012
Results First Submitted Date  ICMJE November 30, 2016
Results First Posted Date  ICMJE January 24, 2017
Last Update Posted Date May 16, 2017
Study Start Date  ICMJE October 2012
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2016)
Change From Baseline in Estimated Glomerular Filtration Rate - Month 12 [ Time Frame: Baseline, Month 12 ]
Evolution of renal function assessed by estimated Glomerular Filtration Rate (eGFR) calculated by the Chronic Kidney Disease in Children (CKiD) Schwartz formula (Schwartz 2009), expressed in mean change in eGFR of CKiD between start of study (baseline assessment) and Month 12.
Original Primary Outcome Measures  ICMJE
 (submitted: May 11, 2012)
Change in Glomerular Filtration Rate [ Time Frame: baseline, 12-month after start of study drug ]
Renal function assessed by estimated Glomerular Filtration Rate 12-month after start of study drug.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2016)
  • Kaplan-Meier Estimates for Failure Rates of Efficacy Endpoints [ Time Frame: At 12-month and 24-month after start of study drug ]
    The proportion of patients with composite efficacy failure (treated biopsy proven acute rejection[tBPAR], graft loss [GL] , death [D]) before/at Month 12 and Month 24, estimated with Kaplan-Meier (KM) methods and the proportion of patients who experienced any of the components of composite efficacy failure (tBPAR, GL, D) before/at Month 12 and Month 24, separately for each component. AR: acute rejection; BPAR: biopsy proven acute rejection. Rate = Kaplan-Meier estimate for failure in %; CI = confidence interval for failure rate.
  • Change From Baseline in Estimated Glomerular Filtration Rate - Month 24 [ Time Frame: Baseline, Month 24 ]
    Evolution of renal function assessed by estimated Glomerular Filtration Rate (eGFR) calculated by the Chronic Kidney Disease in Children (CKiD) Schwartz formula (Schwartz 2009), expressed in mean change in eGFR of CKiD between start of study (baseline assessment) and Month 24.
  • Growth Development - Height at Baseline and Month 12 [ Time Frame: Baseline, Month 12 ]
    Individual growth measurements were compared with the gender and age-specific growth percentiles in the CDC growth charts for the US population. Each value observed is thus represented by the (approximated) percentage of subjects with a lower value in the reference population. Changes were calculated on this scale and thus express the change in growth measurements relative to the percentiles in the CDC growth charts. Patients were classified into growth percentile categories (<=5, >5-25, >25-50, >50-75, >75-95 and >95% percentile).
  • Growth Development - Weight at Baseline and Month 12 [ Time Frame: Baseline, Month 12 ]
    Individual growth measurements were compared with the gender and age-specific growth percentiles in the CDC growth charts for the US population. Each value observed is thus represented by the (approximated) percentage of subjects with a lower value in the reference population. Changes were calculated on this scale and thus express the change in growth measurements relative to the percentiles in the CDC growth charts. Patients were classified into growth percentile categories (<=5, >5-25, >25-50, >50-75, >75-95 and >95% percentile).
  • Growth Development - Weight at Baseline and Month 24 [ Time Frame: Baseline, Month 24 ]
    Individual growth measurements were compared with the gender and age-specific growth percentiles in the CDC growth charts for the US population. Each value observed is thus represented by the (approximated) percentage of subjects with a lower value in the reference population. Changes were calculated on this scale and thus express the change in growth measurements relative to the percentiles in the CDC growth charts. Patients were classified into growth percentile categories (<=5, >5-25, >25-50, >50-75, >75-95 and >95% percentile).
  • Growth Development - Height at Baseline and Month 24 [ Time Frame: Baseline, Month 24 ]
    Individual growth measurements were compared with the gender and age-specific growth percentiles in the CDC growth charts for the US population. Each value observed is thus represented by the (approximated) percentage of subjects with a lower value in the reference population. Changes were calculated on this scale and thus express the change in growth measurements relative to the percentiles in the CDC growth charts. Patients were classified into growth percentile categories (<=5, >5-25, >25-50, >50-75, >75-95 and >95% percentile).
Original Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2012)
  • Rate of composite efficacy failure of treated biopsy proven acute rejection (tBPAR), graft loss (GL) or death (D). [ Time Frame: baseline, 12-month after start of study drug ]
    Efficacy failure rate of tBPAR, GL, or D.at 12-month after start of study drug
  • Number of Adverse Events [ Time Frame: baseline, 12-month and 24-month after start of study drug ]
    AE/SAEs as per preferred term and system organ class Incidence of treatment-related side effects Incidence and reason (e.g. AE) for premature discontinuation of study medication, and premature withdrawal from the study. Incidence and reason (e.g. AE) for dose interruption and dose adjustment of study medication.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients.
Official Title  ICMJE A 24-month, Multi-center, Single Arm, Prospective Study to Evaluate Renal Function, Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients.
Brief Summary This study was designed to assess the evolution of renal function and to collect efficacy, safety, and tolerability data of everolimus in co-exposure with reduced CNI in paediatric liver transplant recipients.
Detailed Description Study is completed (was active and ongoing but no longer recruiting since December 2014). The study Data Monitoring Committee meeting communicated to Novartis the following safety findings in the study population: high rate of premature discontinuation of study medication, high rate of post-transplant lymphoproliferative disease and high rate of related serious infections leading to hospitalization. In light of the safety findings, Novartis followed the DMC recommendation to discontinue the study medication in this age group and to stop enrolling new patients in this study (regardless of age).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Renal Function
  • Liver Transplant
Intervention  ICMJE Drug: Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.
Immunosuppression after liver transplantation. Pediatric transplant recipients received a starting dose of 0.8 mg/m^2/dose in combination wit Cyclosporine A or 2.0 mg/m^2/dose in combination with tacrolimus, twice-daily. Thereafter, doses were adjusted to achieve everolimus C-0h blood trough level between 3 to 8 ng/ml.
Study Arms  ICMJE Experimental: Everolimus based regimen

Conversion at Baseline from an immunosuppressive regimen which contains either cyclosporine (CsA) or tacrolimus (TAC) with or without mycophenolic acid (MPA), with or without corticosteroids in a regimen which contains everolimus combined reduced dose of either cyclosporine (CsA) or tacrolimus (TAC).

The dosing schedule was twice daily, 12 hours apart.

Intervention: Drug: Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 22, 2016)
56
Original Estimated Enrollment  ICMJE
 (submitted: May 11, 2012)
175
Actual Study Completion Date  ICMJE June 2016
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

Signed informed consent from both parents or legal guardian(s) prior to patient participation in the study.

Paediatric liver transplant recipients aged greater than or equal to 1 month and younger than 18 years of age.

Paediatric recipients at the earliest 1 month and latest 6 month after liver transplantation.

Key Exclusion Criteria:

Patients with hepato-biliary malignancies and/or patients transplanted due to fulminant hepatitis /acute liver failure.

Presence of thrombosis of any major hepatic arteries, major/reconstructed hepatic veins, portal vein or inferior vena cava at any time prior to the start of study drug.

Patients with serum creatinine value >2 times age-related ULN at Baseline or who received renal replacement therapy within one week prior to the start of study drug and patients with a confirmed spot urine protein/creatinine ratio indicating a urinary protein excretion >500 mg/m2/24 hrs, at Baseline.

Patients with clinically significant systemic infection and/or in a critical care setting requiring life support measures such as mechanical ventilation, dialysis, or vasopressor agents.

Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.

Pregnant or nursing (lactating) female patients, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive βHCG laboratory test (>9 mIU/mL) at Baseline.

Female patients of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they agree for abstinence from sexual activity.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Month to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Denmark,   France,   Germany,   Hungary,   Italy,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries Argentina
 
Administrative Information
NCT Number  ICMJE NCT01598987
Other Study ID Numbers  ICMJE CRAD001H2305
2011-003069-14
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date April 2017

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