- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00965094
Efficacy and Safety of Everolimus+EC-MPS After Early CNI Elimination vs EC-MPS +Tacrolimus in Renal Transplant Recipients
August 14, 2014 updated by: Novartis Pharmaceuticals
Efficacy and Safety of Certican® (Everolimus) in Combination With Myfortic® (EC-MPS, Enteric-coated Mycophenolate Sodium) After Early CNI Elimination Versus Myfortic® in Combination With Prograf® in Renal Transplant Recipients
The primary objective of this trial is to show non-inferiority of a CNI-free regimen with respect to the renal function at Month 9 post Tx assessed by glomerular filtration rate - Nankivell method - as compared to the standard CNI-based regimen in de novo renal transplant patients.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
36
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Haifa, Israel, 31096
- Novartis Investigative Site
-
Petach Tikva, Israel, 49100
- Novartis Investigative Site
-
Tel-Aviv, Israel, 64239
- Novartis Investigative Site
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion criteria:
- Recipients of de novo cadaveric, living unrelated or living related kidney transplants
- Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at screening, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility.
- Patients who are willing and able to participate in the study and from whom written informed consent has been obtained.
Exclusion criteria:
- More than one previous renal transplantation
- Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney
- Donor age: < 5 years or > 65 years
- Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)
- Patients who had received an investigational drug within 4 weeks of the baseline period
- Patients who are recipients of A-B-O incompatible transplants or T cell cross-match positive transplants
- Patients with already existing antibodies against the HLA-type of the receiving transplant
- Patients with any known hypersensitivity to Simulect®, Certican®, mycophenolic acid, Prograf®, other drugs similar to Certican® (e.g., macrolides), or other components of the formulations.
- Patients who have received an investigational immunosuppressive drug within four weeks prior to study entry (Baseline visit 1)
- Patients with thrombocytopenia (platelets < 75,000/mm³), or an absolute neutrophil count of < 1,500/mm³ or leucopenia (leucocytes < 2,500/mm³), or hemoglobin < 6 g/dL
- Patients with preexisting lung disease (alveolitis, fibrosis) Patients with symptoms of significant somatic or mental illness. Inability to cooperate or communicate with the investigator, who are unlikely to comply with the study requirements, or who are unable to give informed consent
- Patients with a history of malignancy during the last five years, except squamous or basal cell carcinoma of the skin
- Patients who are HIV positive or Hepatitis B surface antigen positive or Hepatitis C virus positive. Recipients of organs from donors who test positive for Hepatitis B surface antigen or Hepatitis C are excluded.
- Evidence of severe liver disease (incl. abnormal liver enzyme profile, i.e. AST, ALT or total bilirubin > 3 times UNL)
- Females of childbearing potential who are planning to become pregnant, who are pregnant or lactating, and/or who are unwilling to use effective means of contraception (see also section 8.2)
- Presence of a clinically significant infection requiring continued therapy, severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus that in the opinion of the investigator would interfere with the appropriate conduct of the study
- Evidence of drug or alcohol abuse
- Patients receiving drugs known to interact with Tacrolimus and/or everolimus according to the list provided in Appendix 3 to this protocol.
- Other protocol-defined inclusion/exclusion criteria may apply
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Everolimus
At BL1, all study patients received induction therapy with basiliximab (Simulect®; 2x20mg on day 0 - 2 hours prior to transplantation, and on day 4 after transplantation) and commenced an immunosuppressive regimen consisting of MPA (Myfortic®; target dose: 1440 mg/day, which was also the maximum daily dose) + tacrolimus (Prograf®; based on C0-h levels; Table 9-2) and with corticosteroids.
AT BL2 [Month 3 (+1 week) after transplantation], eligible patients were randomized, using living and cadaveric donation as stratum.
Patients were switched to the CNI-free regimen.
Everolimus was added to the patients immunosuppressive regimen and tacrolimus was removed successively.
|
One tablet containing 0.25, 0.5mg or 0.75 mg.
Initially 2 mg/day.
Afterwards based on blood level (target 6-10 ng/mL)
Other Names:
One vial containing 20 mg lyophilisate.
2 x 20 mg [day 0 (2 hrs prior to Tx) and day 4 post Tx] to be applied as 10 sec.
bolus injection, i.v.
Other Names:
One tablet containing 180 mg or 360 mg.
1440 mg/day (2x720 mg).
If tolerated, dose reduction due to side effectis were possible (min.
dose at BL@: 720 mg/day)
Other Names:
Used according to Israeli standards.
A minimum dose of 5mg [prednisone, or equivalent, was used throughout the study period.
|
Active Comparator: Reference Therapy
At BL1, all study patients received induction therapy with basiliximab (Simulect®; 2x20mg on day 0 - 2 hours prior to transplantation, and on day 4 after transplantation) and commenced an immunosuppressive regimen consisting of MPA (Myfortic®; target dose: 1440 mg/day, which was also the maximum daily dose) + tacrolimus (Prograf®; based on C0-h levels; Table 9-2) and with corticosteroids.
AT BL2 [Month 3 (+1 week) after transplantation], eligible patients were randomized, using living and cadaveric donation as stratum.
Patients continued on the prior immunosuppressive regimen consisting of MPA + tacrolimus with corticosteroids.
|
One vial containing 20 mg lyophilisate.
2 x 20 mg [day 0 (2 hrs prior to Tx) and day 4 post Tx] to be applied as 10 sec.
bolus injection, i.v.
Other Names:
One tablet containing 180 mg or 360 mg.
1440 mg/day (2x720 mg).
If tolerated, dose reduction due to side effectis were possible (min.
dose at BL@: 720 mg/day)
Other Names:
Used according to Israeli standards.
A minimum dose of 5mg [prednisone, or equivalent, was used throughout the study period.
Capsules 0.5 mg, 1 mg.
Dosing according to blood level.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Renal Function Assessed as Glomerula Filtration Rate (GFR) - Nankivell Method - 9 Months After Renal Transplantation (LOCF)
Time Frame: 9 months
|
The glomerular filtration rate (GFR) is the best clinical estimate of renal function in health and disease, and correlates well with the clinical severity of renal function disturbances.
The GFR, calculated according to the Nankivell formula, was used as the primary outcome measure in this study.
This equation has been validated in renal transplant patients against the true GFR measured by a radionuclide method and has been confirmed as a very accurate method to calculate the GFR in this specific population (Gaspari et al., 2004)GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C Scr = serum creatinine concentration expressed in mmol/L.
BW = body weight in kg, Surea = serum urea in mmol/L and Height is expressed in meters.The
Last Observation Carried Forward (LOCF) imputation technique was used for this analysis.
|
9 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assessment of GFR by the Cockcroft-Gault Method (LOCF)
Time Frame: 9 months
|
the GFR was also calculated using the Cockcroft-Gault method (Cockcroft and Gault 1976) and the Modification of Diet in Renal Disease (MDRD) method (Levey et al., 1999, Rodrigo et al., 2003; Pierrat et al., 2003).Cockcroft-Gault formula For men: GFR= (140-Age)X Body Weight[kg]/72X Serum Creatinine[mg/dl] For women: GFR= 0,85x(140-Age) x Body Weight[kg]/72x Serum Creatinine [mg/dl] The Last Observation Carried Forward (LOCF) imputation technique was used for this analysis.
|
9 months
|
Participants Who Had Occurrence of Biopsy Proven Acute Rejection, Graft Loss or Death.
Time Frame: 9 months
|
Biopsy-proven acute rejection was defined as a biopsy gradeed IA, IB, IIA, IIB, or III.
The allograft was presumed to be lost if the patient started dialysis and was not able to subsequently be removed from dialysis.
If the patient underwent a graft nephrectomy, then the day of nephrectomy was the day of graft loss.
|
9 months
|
Participants Who Had Occurrence of Treatment Failure.
Time Frame: 9 months
|
Treatment failure was defined as a composite endpoint of biopsy-proven acute rejection, graft loss, death, loss to follow up, discontinuation due to lack of efficacy or toxicity or conversion to another regimen.
|
9 months
|
Change in Renal Function (Creatinine Slope)
Time Frame: 3 months, 5 months, 7 months, 9 months
|
X(slope)=(1/value of creatinine).
|
3 months, 5 months, 7 months, 9 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2009
Primary Completion (Actual)
June 1, 2013
Study Completion (Actual)
June 1, 2013
Study Registration Dates
First Submitted
August 24, 2009
First Submitted That Met QC Criteria
August 24, 2009
First Posted (Estimate)
August 25, 2009
Study Record Updates
Last Update Posted (Estimate)
August 15, 2014
Last Update Submitted That Met QC Criteria
August 14, 2014
Last Verified
August 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Kidney Diseases
- Urologic Diseases
- Renal Insufficiency
- Renal Insufficiency, Chronic
- Kidney Failure, Chronic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Tacrolimus
- Mycophenolic Acid
- Everolimus
- Basiliximab
Other Study ID Numbers
- CRAD001AIL03
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Renal Failure
-
University of Sao Paulo General HospitalUnknownRenal Transplant Rejection | Graft Failure | Transplant; Failure, Kidney | Chronic Renal Failure (CRF)Brazil
-
Angiodynamics, Inc.TerminatedChronic Kidney Disease | Acute Kidney Injury | Acute Renal Failure | Renal Failure Chronic Contrast InducedUnited States
-
Rockwell Medical Technologies, Inc.CompletedRenal Failure Chronic Requiring HemodialysisUnited States, Puerto Rico
-
Rockwell Medical Technologies, Inc.CompletedRenal Failure Chronic Requiring HemodialysisUnited States, Canada
-
PfizerCompletedChronic Renal Failure Requiring HemodialysisUnited States, Puerto Rico
-
University of PennsylvaniaTeleflex; Arrow InternationalCompletedRenal Failure Chronic Requiring Hemodialysis | Chronic Renal InsufficiencyUnited States
-
Esraa Ahmed MohamedUnknownEvaluations of Sexual Dysfunction of Female in Chronic Renal Failure
-
Shenyang Sunshine Pharmaceutical Co., LTD.UnknownChronic Renal Failure With HemodialysisChina
-
PfizerCompletedChronic Renal Failure Requiring HemodialysisUnited States
-
University of CologneCompletedRenal Failure Chronic Contrast InducedGermany
Clinical Trials on Everolimus
-
Novartis PharmaceuticalsTerminatedHepatocellular CarcinomaHong Kong, Taiwan, Thailand
-
German Breast GroupNovartisTerminatedMetastatic Breast CancerGermany
-
The Netherlands Cancer InstituteActive, not recruitingNeuroendocrine CarcinomasNetherlands
-
Novartis PharmaceuticalsCompletedLymphangioleiomyomatosis (LAM) | Tuberous Sclerosis Complex (TSC)United States, United Kingdom, Germany, Italy, Russian Federation, Netherlands, Japan, Canada, Poland, France, Spain
-
University of LuebeckTerminatedCoronary Artery DiseaseGermany
-
Guangdong Provincial People's HospitalNovartisUnknownNeuroendocrine Tumors | Carcinoid TumorChina
-
Novartis PharmaceuticalsCompletedGastroenteropancreatic Neuroendocrine Tumor of the Pulmonary ot Gastroenteropancreatic SystemGermany
-
Novartis PharmaceuticalsTerminatedCarcinoma, Renal CellAustralia, Korea, Republic of
-
Centre Leon BerardSuspended
-
Leiden University Medical CenterUnknownHead and Neck CancerNetherlands