Chronic Renal FailurePhase 4NCT00965094
Efficacy and Safety of Everolimus+EC-MPS After Early CNI Elimination vs EC-MPS +Tacrolimus in Renal Transplant Recipients
A Phase 4 study testing Everolimus, Tacrolimus (FK506) and Basiliximab in people with Chronic Renal Failure, run by Novartis Pharmaceuticals at 3 sites in Israel.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Renal Failure
- What is being tested?
- Everolimus, Tacrolimus (FK506) and Basiliximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 3 sitesIsrael
- Study dates
- Dec 2009to Jun 2013
- Phase
- Phase 4
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
Israel3 sites
Novartis Investigative Site
Haifa, 31096
Novartis Investigative Site
Petah Tikva, 49100
Novartis Investigative Site
Tel Aviv, 64239
About this study
Official title: 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.
- Conditions
- Chronic Renal Failure
- Being tested
- Everolimus, Tacrolimus (FK506), Basiliximab, Enteric Coated Mycophenolate Sodium (EC-MPS), Corticosteroids
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Certican
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)
Tacrolimus (FK506)Drug
Also called Prograf
Capsules 0.5 mg, 1 mg. Dosing according to blood level.
BasiliximabDrug
Also called Simulect
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.
Enteric Coated Mycophenolate Sodium (EC-MPS)Drug
Also called Myfortic
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)
CorticosteroidsDrug
Used according to Israeli standards. A minimum dose of 5mg [prednisone, or equivalent, was used throughout the study period.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | 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. Receives: Drug: Everolimus; Drug: Basiliximab; Drug: Enteric Coated Mycophenolate Sodium (EC-MPS); Drug: Corticosteroids |
| Reference Therapy | Active comparator | 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. Receives: Drug: Tacrolimus (FK506); Drug: Basiliximab; Drug: Enteric Coated Mycophenolate Sodium (EC-MPS); Drug: Corticosteroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal Function Assessed as Glomerula Filtration Rate (GFR) - Nankivell Method - 9 Months After Renal Transplantation (LOCF)
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.
Measured: 9 months
Secondary outcomes (4)
Assessment of GFR by the Cockcroft-Gault Method (LOCF)
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.
Measured: 9 months
Participants Who Had Occurrence of Biopsy Proven Acute Rejection, Graft Loss or Death.
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.
Measured: 9 months
Participants Who Had Occurrence of Treatment Failure.
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.
Measured: 9 months
Change in Renal Function (Creatinine Slope)
X(slope)=(1/value of creatinine).
Measured: 3 months, 5 months, 7 months, 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2009 (estimated)
- Study startDec 2009
- Primary completionJun 2013
- Study completionJun 2013
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Renal FailureStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 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
- NCT00965094
- Sponsor's protocol ID
- CRAD001AIL03
- Status last verified
- Aug 2014
- First submitted
- 24 Aug 2009
- Last updated
- 15 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Bemelman FJ, de Maar EF, Press RR, van Kan HJ, ten Berge IJ, Homan van der Heide JJ, de Fijter HW. Minimization of maintenance immunosuppression early after renal transplantation: an interim analysis. Transplantation. 2009 Aug 15;88(3):421-8. doi: 10.1097/TP.0b013e3181af1df6.
PubMed 19667948
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00965094
- Acronym / sponsor ID
- CRAD001AIL03
- Conditions
- Chronic Renal Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 25 Aug 2009 (estimated)
- Results
- Posted 15 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: Everolimus, Drug: Basiliximab, Drug: Enteric Coated Mycophenolate Sodium (EC-MPS), Drug: CorticosteroidsAt 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. |
| Reference Therapy | Active comparator | Drug: Tacrolimus (FK506), Drug: Basiliximab, Drug: Enteric Coated Mycophenolate Sodium (EC-MPS), Drug: CorticosteroidsAt 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (19 listed)
- 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
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 |
|---|---|---|
| EverolimusAlso: CerticanOne tablet containing 0.25, 0.5mg or 0.75 mg. Initially 2 mg/day. Afterwards based on blood level (target 6-10 ng/mL) | Drug | Everolimus |
| Tacrolimus (FK506)Also: PrografCapsules 0.5 mg, 1 mg. Dosing according to blood level. | Drug | Reference Therapy |
| BasiliximabAlso: SimulectOne 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. | Drug | Everolimus, Reference Therapy |
| Enteric Coated Mycophenolate Sodium (EC-MPS)Also: MyforticOne 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) | Drug | Everolimus, Reference Therapy |
| CorticosteroidsUsed according to Israeli standards. A minimum dose of 5mg [prednisone, or equivalent, was used throughout the study period. | Drug | Everolimus, Reference Therapy |
Primary outcome
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.
4 secondary outcomes
Assessment of GFR by the Cockcroft-Gault Method (LOCF)
Time frame: 9 months
Participants Who Had Occurrence of Biopsy Proven Acute Rejection, Graft Loss or Death.
Time frame: 9 months
Participants Who Had Occurrence of Treatment Failure.
Time frame: 9 months
Change in Renal Function (Creatinine Slope)
Time frame: 3 months, 5 months, 7 months, 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19667948Bemelman FJ, de Maar EF, Press RR, van Kan HJ, ten Berge IJ, Homan van der Heide JJ, de Fijter HW. Minimization of maintenance immunosuppression early after renal transplantation: an interim analysis. Transplantation. 2009 Aug 15;88(3):421-8. doi: 10.1097/TP.0b013e3181af1df6.
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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
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Everolimus, Tacrolimus (FK506) and Basiliximab in people with Chronic Renal Failure, run by Novartis Pharmaceuticals at 3 sites in Israel.
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 19 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 15 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Israel. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 15 Aug 2014). 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?
Renal Function Assessed as Glomerula Filtration Rate (GFR) - Nankivell Method - 9 Months After Renal Transplantation (LOCF) (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00965094, which also lists 1 linked publication.
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 15 Aug 2014.