Renal FunctionPhase 3NCT01598987
Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients.
A Phase 3 study testing Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation. in people with Renal Function and Liver Transplant, run by Novartis Pharmaceuticals at 32 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 month to 17 years
- Conditions the study is for
- Renal Function, Liver Transplant
- What is being tested?
- Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 32 sitesin 12 countries
- Study dates
- Oct 2012to Jun 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
32 sites in 12 countries.
32 sites in 12 countries
United States9 sites
Novartis Investigative Site
Charleston, South Carolina, 29425
Novartis Investigative Site
Chicago, Illinois, 60637
Novartis Investigative Site
Houston, Texas, 77030-2400
Novartis Investigative Site
Los Angeles, California, 90027
Novartis Investigative Site
Madison, Wisconsin, 53792
Novartis Investigative Site
New Haven, Connecticut, 06520
Novartis Investigative Site
New York, New York, 110032
Novartis Investigative Site
Salt Lake City, Utah, 84132
Novartis Investigative Site
St Louis, Missouri, 63110
Germany6 sites
Novartis Investigative Site
Bonn, 53105
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Hanover, Germany, 30625
Novartis Investigative Site
Regensburg, 93053
Novartis Investigative Site
Tübingen, 72076
Italy4 sites
Novartis Investigative Site
Bergamo, BG, 24128
Novartis Investigative Site
Padova, PD, 35128
Novartis Investigative Site
Roma, ITA, 00165
Novartis Investigative Site
Torino, TO, 10126
United Kingdom3 sites
Novartis Investigative Site
Leeds, LS1 3EX
Novartis Investigative Site
London, SE5 9RS
Novartis Investigative Site
West Midlands, Birmingham, B4 6NH
Hungary2 sites
Novartis Investigative Site
Budapest, 1082
Novartis Investigative Site
Budapest, 1083
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, Madrid, 28046
About this study
Official title: 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.
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.
Read the 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).
- Conditions
- Renal Function, Liver Transplant
- Being tested
- Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.
- Keywords
- Paediatric liver transplantation, Everolimus, Reduced calcineurin inhibitor, Cyclosporine, tacrolimus, Renal function, Composite efficacy endpoint (treated biopsy proven acute rejection death, graft loss), Liver transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.Drug
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 group | Role | What they receive |
|---|---|---|
| Everolimus based regimen | Experimental | 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. Receives: Drug: Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Estimated Glomerular Filtration Rate - 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.
Measured: Baseline, Month 12
Secondary outcomes (6)
Kaplan-Meier Estimates for Failure Rates of Efficacy Endpoints
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.
Measured: At 12-month and 24-month after start of study drug
Change From Baseline in Estimated Glomerular Filtration Rate - 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.
Measured: Baseline, Month 24
Growth Development - Height at Baseline and 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).
Measured: Baseline, Month 12
Growth Development - Weight at Baseline and 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).
Measured: Baseline, Month 12
Growth Development - Weight at Baseline and 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).
Measured: Baseline, Month 24
Growth Development - Height at Baseline and 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).
Measured: Baseline, Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2012 (estimated)
- Study startOct 2012
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Renal FunctionStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01598987
- Sponsor's protocol ID
- CRAD001H2305
- Other IDs
- 2011-003069-14
- Status last verified
- Apr 2017
- First submitted
- 1 Mar 2012
- Last updated
- 16 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT01598987
- Acronym / sponsor ID
- CRAD001H2305
- Conditions
- Renal Function, Liver Transplant
- Keywords
- Paediatric liver transplantation, Everolimus, Reduced calcineurin inhibitor, Cyclosporine, tacrolimus, Renal function, Composite efficacy endpoint (treated biopsy proven acute rejection death, graft loss), Liver transplant
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 15 May 2012 (estimated)
- Results
- Posted 24 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus based regimen | Experimental | Drug: Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.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. |
Who may qualify
- Ages
- 1 month to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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 (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Everolimus based regimen |
Primary outcome
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.
6 secondary outcomes
Kaplan-Meier Estimates for Failure Rates of Efficacy Endpoints
Time frame: At 12-month and 24-month after start of study drug
Change From Baseline in Estimated Glomerular Filtration Rate - Month 24
Time frame: Baseline, Month 24
Growth Development - Height at Baseline and Month 12
Time frame: Baseline, Month 12
Growth Development - Weight at Baseline and Month 12
Time frame: Baseline, Month 12
Growth Development - Weight at Baseline and Month 24
Time frame: Baseline, Month 24
Growth Development - Height at Baseline and Month 24
Time frame: Baseline, Month 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Renal Function
Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
Not yet recruitingPhase 2
REducing Systemic Inflammation With LOw-dose Colchicine to ImproVE Cardiovascular Calcification in Chronic Kidney Disease: A Pilot Randomized Open-Label Trial
Chronic Kidney Disease Mineral and Bone Disorder, Cognitive Function
Not yet recruiting
Bioimpedance and Multiparametric Ultrasound-Guided Fluid Management After Kidney Transplantation
Kidney Transplantation, Delayed Graft Function
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Recruiting
Urinary Creatinine Excretion Time in the Neonatal Period
Renal Function
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
32 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation. in people with Renal Function and Liver Transplant, run by Novartis Pharmaceuticals at 32 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Germany, Italy, United Kingdom, Hungary and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Estimated Glomerular Filtration Rate - Month 12 (time frame: Baseline, Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2017.