Renal TransplantationPhase 4NCT00332839
Comparison of CNI-based Regimen Versus CNI-free Regimen in Kidney Transplant Recipients.
A Phase 4 study testing Everolimus, Cyclosporin A (CsA) and Tacrolimus in people with Renal Transplantation, run by Novartis Pharmaceuticals at 11 sites in Germany.
Trial summary
Calcineurin inhibitors (CNI), a potent immunosuppressive drug used in kidney transplant recipients to prevent graft rejection, may cause renal impairment. The aim of this study is to assess whether a CNI-free regimen with enteric-coated mycophenolate sodium and everolimus is as safe and well tolerated as a standard… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Transplantation
- What is being tested?
- Everolimus, Cyclosporin A (CsA) and Tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 93 participants
- Where
- 11 sitesGermany
- Study dates
- Nov 2005to Mar 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females, aged > 18 years, Maintenance renal transplant recipients at least 6 months post-transplantation, Patients with a serum creatinine < 2,5 mg/dL stable for at least three month (according to the investigator), Females capable of becoming pregnant had to have a negative serum pregnancy test within seven days prior to or at baseline, and were required to practice an approved method of birth control for the duration of the study and for a period of six weeks following discontinuation of study medication, even where there had been a history of infertility, Patients receiving Myfortic® (Myfortic dose . 720 mg/d) and Sandimmun® Optoral with or without corticosteroids as part of their immunosuppressive regimen for at least 1 month before baseline;
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, Patient with proteinuria > 1000 mg/day at baseline, Hypersensitivity to Certican®, Sandimmun® Optoral, Prograf®, mycophenolic acid, or other components of the formulation, Patients who had received an investigational drug within four weeks prior to baseline, Severe rejection (≥ Banff II acute rejection), recurrent acute rejection, or steroid resistant rejection within six months of enrollment, Thrombocytopenia (platelets < 100,000/mm³), with an absolute neutrophil count of < 1,500/mm³ or leukopenia (leukocytes < 4,000/mm³), or hemoglobin < 8 g/dL, Abnormal physical or laboratory findings of clinical significance within two weeks of study inclusion which at the investigator's discretion would interfere with the objectives of the study, Symptoms of significant somatic or mental illness. Inability to cooperate or communicate with the investigator, or patients who were unlikely to comply with the study requirements, or who were unable to give informed consent, History of malignancy during the last five years, except squamous or basal cell carcinoma of the skin, Patients who were HIV positive, or hepatitis C, or hepatitis B surface antigen positiveEvidence of severe liver disease (including abnormal liver enzyme profile, i.e. aspartate transaminase (AST), alanine aminotransferase (ALT) or total bilirubin > 3 times upper limit of normal (ULN), Females of childbearing potential who were planning to become pregnant, who were pregnant or lactating and/or who were unwilling to use effective means of contraception, 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
- Other protocol-defined exclusion criteria may apply.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Germany11 sites
Novartis Investigative Site
Berlin, 10098
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Cologne, 51109
Novartis Investigative Site
Erlangen, 91054
Novartis Investigative Site
Essen, 45122
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Heidelberg, 69115
Novartis Investigative Site
Heilbronn, 74076
Novartis Investigative Site
Kaiserslautern, 67655
Novartis Investigative Site
Kiel, 24105
Novartis Investigative Site
Münster, 48149
About this study
Official title: Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a CNI-free Regimen With Enteric-coated Mycophenolate Sodium and Everolimus in Comparison to Standard Therapy With Enteric-coated Mycophenolate Sodium and Ciclosporin Microemulsion in Stable Renal Transplant Patients
Calcineurin inhibitors (CNI), a potent immunosuppressive drug used in kidney transplant recipients to prevent graft rejection, may cause renal impairment. The aim of this study is to assess whether a CNI-free regimen with enteric-coated mycophenolate sodium and everolimus is as safe and well tolerated as a standard regimen consisting of enteric-coated mycophenolate sodium and cyclosporine microemulsion without a compromise in therapeutic efficacy while resulting in an improved renal function.
- Conditions
- Renal Transplantation
- Being tested
- Everolimus, Cyclosporin A (CsA), Tacrolimus, Enteric Coated - Mycophenolate Sodium (EC-MPS), Corticosteroids
- Keywords
- enteric-coated mycophenolate sodium, everolimus, CNI-free regimen
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called RAD001, Certican
Participants, switching from the CsA based treatment, initially received everolimus 1.5 mg/day and then from day 7, 3 mg/day, and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml). Participants, switching from the tacrolimus based treatment, initially received 3 mg/day and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml).
Cyclosporin A (CsA)Drug
Also called Sandimmun Optoral
The dose was based on the participants' blood level of C0h (80-150 ng/ml).
TacrolimusDrug
Also called Prograf
The dose was based on the participants' blood level of C0h (5-10 ng/ml).
Enteric Coated - Mycophenolate Sodium (EC-MPS)Drug
Also called Myfortic
The dose was ≥ 720 mg/day.
CorticosteroidsDrug
Corticosteroids were given according to local standard and/or the Investigators' discretion.
| Study group | Role | What they receive |
|---|---|---|
| Calcineurin Inhibitor (CNI) group | Active comparator | Participants received Cyclosporine A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids, or Tacrolimus A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids. Receives: Drug: Cyclosporin A (CsA); Drug: Tacrolimus; Drug: Enteric Coated - Mycophenolate Sodium (EC-MPS); Drug: Corticosteroids |
| Certican group | Experimental | Participants were switched in a step-wise fashion from the CNI based regimen to Everolimus (RAD001). Receives: Drug: Everolimus; 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
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Measured: 12 months
Secondary outcomes (6)
Biopsy Proven Acute Rejection, Graft Loss, and Death
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Measured: 12 months
Occurrence of Treatment Failures
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Measured: 12 months
Evolution of Renal Function
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Measured: Baseline, 12 months
Number of Participants Who Experienced Adverse Events and Death
Participants were monitored for adverse events, serious adverse events and deaths thorughout the prospective and follow-up phases of the study.
Measured: 12 months
Changes in Cardiovascular Risk
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Measured: Baseline, 12 months
Changes in Proteinuria
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Measured: Baseline, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2006 (estimated)
- Study startNov 2005
- Primary completionMar 2013
- Study completionMar 2013
Why it stopped: The trial was terminated early due to slow enrollment. It was determined that the planned sample size of 300 could not be achieved.
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 TransplantationStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis PharmaceuticalsNovartis, Study director, Novartis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00332839
- Sponsor's protocol ID
- CRAD001ADE02
- Other IDs
- 2005-001013-18, 2005
- Status last verified
- Aug 2014
- First submitted
- 31 May 2006
- Last updated
- 28 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a CNI-free Regimen With Enteric-coated Mycophenolate Sodium and Everolimus in Comparison to Standard Therapy With Enteric-coated Mycophenolate Sodium and Ciclosporin Microemulsion in Stable Renal Transplant Patients
- ClinicalTrials.gov ID
- NCT00332839
- Acronym / sponsor ID
- CRAD001ADE02
- Conditions
- Renal Transplantation
- Keywords
- enteric-coated mycophenolate sodium, everolimus, CNI-free regimen
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was terminated early due to slow enrollment. It was determined that the planned sample size of 300 could not be achieved.
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2005
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 2 Jun 2006 (estimated)
- Results
- Posted 28 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Calcineurin inhibitors (CNI), a potent immunosuppressive drug used in kidney transplant recipients to prevent graft rejection, may cause renal impairment. The aim of this study is to assess whether a CNI-free regimen with enteric-coated mycophenolate sodium and everolimus is as safe and well tolerated as a standard regimen consisting of enteric-coated mycophenolate sodium and cyclosporine microemulsion without a compromise in therapeutic efficacy while resulting in an improved renal function.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Calcineurin Inhibitor (CNI) group | Active comparator | Drug: Cyclosporin A (CsA), Drug: Tacrolimus, Drug: Enteric Coated - Mycophenolate Sodium (EC-MPS), Drug: CorticosteroidsParticipants received Cyclosporine A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids, or Tacrolimus A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids. |
| Certican group | Experimental | Drug: Everolimus, Drug: Enteric Coated - Mycophenolate Sodium (EC-MPS), Drug: CorticosteroidsParticipants were switched in a step-wise fashion from the CNI based regimen to Everolimus (RAD001). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Males or females, aged > 18 years, Maintenance renal transplant recipients at least 6 months post-transplantation, Patients with a serum creatinine < 2,5 mg/dL stable for at least three month (according to the investigator), Females capable of becoming pregnant had to have a negative serum pregnancy test within seven days prior to or at baseline, and were required to practice an approved method of birth control for the duration of the study and for a period of six weeks following discontinuation of study medication, even where there had been a history of infertility, Patients receiving Myfortic® (Myfortic dose . 720 mg/d) and Sandimmun® Optoral with or without corticosteroids as part of their immunosuppressive regimen for at least 1 month before baseline;
Key exclusion criteria (2 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, Patient with proteinuria > 1000 mg/day at baseline, Hypersensitivity to Certican®, Sandimmun® Optoral, Prograf®, mycophenolic acid, or other components of the formulation, Patients who had received an investigational drug within four weeks prior to baseline, Severe rejection (≥ Banff II acute rejection), recurrent acute rejection, or steroid resistant rejection within six months of enrollment, Thrombocytopenia (platelets < 100,000/mm³), with an absolute neutrophil count of < 1,500/mm³ or leukopenia (leukocytes < 4,000/mm³), or hemoglobin < 8 g/dL, Abnormal physical or laboratory findings of clinical significance within two weeks of study inclusion which at the investigator's discretion would interfere with the objectives of the study, Symptoms of significant somatic or mental illness. Inability to cooperate or communicate with the investigator, or patients who were unlikely to comply with the study requirements, or who were unable to give informed consent, History of malignancy during the last five years, except squamous or basal cell carcinoma of the skin, Patients who were HIV positive, or hepatitis C, or hepatitis B surface antigen positiveEvidence of severe liver disease (including abnormal liver enzyme profile, i.e. aspartate transaminase (AST), alanine aminotransferase (ALT) or total bilirubin > 3 times upper limit of normal (ULN), Females of childbearing potential who were planning to become pregnant, who were pregnant or lactating and/or who were unwilling to use effective means of contraception, 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
- Other protocol-defined exclusion criteria may apply.
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: RAD001, CerticanParticipants, switching from the CsA based treatment, initially received everolimus 1.5 mg/day and then from day 7, 3 mg/day, and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml). Participants, switching from the tacrolimus based treatment, initially received 3 mg/day and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml). | Drug | Certican group |
| Cyclosporin A (CsA)Also: Sandimmun OptoralThe dose was based on the participants' blood level of C0h (80-150 ng/ml). | Drug | Calcineurin Inhibitor (CNI) group |
| TacrolimusAlso: PrografThe dose was based on the participants' blood level of C0h (5-10 ng/ml). | Drug | Calcineurin Inhibitor (CNI) group |
| Enteric Coated - Mycophenolate Sodium (EC-MPS)Also: MyforticThe dose was ≥ 720 mg/day. | Drug | Calcineurin Inhibitor (CNI) group, Certican group |
| CorticosteroidsCorticosteroids were given according to local standard and/or the Investigators' discretion. | Drug | Calcineurin Inhibitor (CNI) group, Certican group |
Primary outcome
Renal Function
Time frame: 12 months
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
6 secondary outcomes
Biopsy Proven Acute Rejection, Graft Loss, and Death
Time frame: 12 months
Occurrence of Treatment Failures
Time frame: 12 months
Evolution of Renal Function
Time frame: Baseline, 12 months
Number of Participants Who Experienced Adverse Events and Death
Time frame: 12 months
Changes in Cardiovascular Risk
Time frame: Baseline, 12 months
Changes in Proteinuria
Time frame: Baseline, 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
Novartis study director
Novartis
11 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, Cyclosporin A (CsA) and Tacrolimus in people with Renal Transplantation, run by Novartis Pharmaceuticals at 11 sites in Germany.
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 1 inclusion and 2 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: stopped early, as of the sponsor's last update on 28 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 11 sites in Germany. 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 28 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 (time frame: 12 months). 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 28 Aug 2014.