Renal TransplantationPhase 4SenatorNCT00956293
Study to Evaluate the Efficacy, Safety and Tolerability of Everolimus in de Novo Renal Transplant Recipients Participating in the Eurotransplant Senior Program
A Phase 4 study testing Basiliximab, Enteric Coated Mycophenolic Acid (MPA) and RAD001 in people with Renal Transplantation, run by Novartis Pharmaceuticals at 9 sites in Germany.
Trial summary
This study wants to address whether a calcineurin-inhibitor (CNI)-free regimen six weeks after transplantation for Eurotransplant Senior Program (ESP) patients is as safe and well tolerated as standard treatment but optimizing immunosuppressive therapy with benefits in renal function, new-onset diabetes mellitus… Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Renal Transplantation
- What is being tested?
- Basiliximab, Enteric Coated Mycophenolic Acid (MPA) and RAD001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 207 participants
- Where
- 9 sitesGermany
- Study dates
- Jul 2009to 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Patients receiving a primary kidney from a donor aged > 65 years
- In the Eurotransplant Senior Program
- Recipients of de novo cadaveric kidney transplants
Who cannot join
- Multi-organ recipients (e.g., kidney and pancreas)
- Patients receiving a kidney from a non-heart beating donor
- Patients who are recipients of A-B-O incompatible transplants
- Patients with already existing antibodies against the HLA-type of the receiving transplant
- Patients who have received an investigational immunosuppressive drug within four weeks prior to study entry (Baseline visit 1)
- Patients with thrombocytopenia, with an absolute neutrophil count of < 1,500/mm³ or leucopenia or hemoglobin < 6 g/dL
Show all 10Show fewer
- Patients who are HIV, HCV RNA, or Hepatitis B surface antigen positive
- Evidence of severe liver disease
- Females at randomization who will be not considered post-menopausal
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Germany9 sites
Novartis Investigative Site
Aachen, 52074
Novartis Investigative Site
Berlin, 10117
Novartis Investigative Site
Düsseldorf, 40225
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Kaiserslautern, 67655
Novartis Investigative Site
Koeln-Merheim, 51109
Novartis Investigative Site
München, 81377
About this study
Official title: 6-month, Open-label, Randomized, Multicenter, Prospective, Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Everolimus in de Novo Renal Transplant Recipients Participating in the Eurotransplant Senior Program
This study wants to address whether a calcineurin-inhibitor (CNI)-free regimen six weeks after transplantation for Eurotransplant Senior Program (ESP) patients is as safe and well tolerated as standard treatment but optimizing immunosuppressive therapy with benefits in renal function, new-onset diabetes mellitus, cardiovascular risk, cancer and allograft nephropathy.
- Conditions
- Renal Transplantation
- Being tested
- Basiliximab, Enteric Coated Mycophenolic Acid (MPA), RAD001, Cyclosporin A (CsA), Corticosteroids
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BasiliximabDrug
Also called Simulect
On day 0, 2 hours prior to transplant and day 4 post-transplant, 20 mg x2 were given to all participants. Post randomization, 20mg at weeks 7 and 12 were given to the Everolimus group.
Enteric Coated Mycophenolic Acid (MPA)Drug
Also called Myfortic
A loading dose regimen of 2880 mg/day during weeks 1 and 2 (pre-randomization) were given. During weeks 3 - 6 (pre-randomization), 2160 mg/day were given and during weeks 7 - 24, 1440 mg/day were given if tolerated. Dose reductions due to side effects were possible.
RAD001Drug
Also called RAD001, Certcian
Upon randomization, 3 mg (od) on Day 1, and 3 mg (1.5 mg every 12 hours) on Day 2 was given. Afterwards, the dosage was based on blood trough level (5 - 10 ng/mL).
Cyclosporin A (CsA)Drug
Also called Sandimmun Optoral
Dosage was based according to blood level
CorticosteroidsDrug
Dosage was administered according to local standards and administration was optional as per clinical need and the Investigators' discretion. Steroid withdrawal occurred after week 2 (pre-randomization).
| Study group | Role | What they receive |
|---|---|---|
| Control group | Active comparator | During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group continued with a CNI-based regimen of MPA and CsA. Receives: Drug: Basiliximab; Drug: Enteric Coated Mycophenolic Acid (MPA); Drug: Cyclosporin A (CsA); Drug: Corticosteroids |
| Everolimus group | Experimental | During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group made a stepwise switch to a CNI-free regimen of everolimus and MPA. Receives: Drug: Basiliximab; Drug: Enteric Coated Mycophenolic Acid (MPA); Drug: RAD001; Drug: Cyclosporin A (CsA); Drug: Corticosteroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal Function by Glomerular Filtration Rate (GFR) Via Cockcroft-Gault Method
The study was terminated prematurely and not powered for efficacy.
Measured: Month 6
Secondary outcomes (9)
Renal Function by GFR Via Modification of Diet in Renal Diseases (MDRD) and Nankivell Method
The study was terminated prematurely and not powered for efficacy.
Measured: Month 6
Renal Function by Serum Creatinine
The study was terminated prematurely and not powered for efficacy.
Measured: Months 6, 12, 24, 36, 48 and 60
Biopsy Proven Acute Rejection (BPAR), Graft Loss and Death
The study was terminated prematurely and not powered for efficacy.
Measured: Months 6, 12, 24, 36, 48 and 60
Occurrence of Treatment Failures
The study was terminated prematurely and not powered for efficacy.
Measured: Month 6
Evolution of Renal Function (Creatinine Slope)
The study was terminated prematurely and not powered for efficacy.
Measured: Week 7, Month 6
CD25 Saturation on Lymphocytes
Measured: Month 6
Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death
Participants with adverse events (serious plus non-serious), serious adverse events and death were reported.
Measured: Months 6, 12, 24, 36, 48 and 60
Renal Function by GFR Over Time
Measured: Months 12, 24, 36, 48 and 60
Renal Function by Proteinuria
Measured: Months12, 24, 36, 48 and 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2009 (estimated)
- Study startJul 2009
- Primary completionMar 2013
- Study completionMar 2013
Why it stopped: The study was terminated because the required sample size of 240-260 de novo senior renal transplant patients was not achieved within a reasonable time.
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 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 207 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
- NCT00956293
- Sponsor's protocol ID
- CRAD001ADE19
- Other IDs
- EudraCT-NO. 2008-005109-20, 2008-005109-20, 2008
- Acronym
- Senator
- Status last verified
- May 2014
- First submitted
- 7 Aug 2009
- Last updated
- 6 Jun 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Brakemeier S, Arns W, Lehner F, Witzke O, Vonend O, Sommerer C, Muhlfeld A, Rath T, Schuhmann R, Zukunft B, Kroeger I, Porstner M, Budde K. Everolimus in de novo kidney transplant recipients participating in the Eurotransplant senior program: Results of a prospective randomized multicenter study (SENATOR). PLoS One. 2019 Sep 19;14(9):e0222730. doi: 10.1371/journal.pone.0222730. eCollection 2019.
PubMed 31536556
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 6-month, Open-label, Randomized, Multicenter, Prospective, Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Everolimus in de Novo Renal Transplant Recipients Participating in the Eurotransplant Senior Program
- ClinicalTrials.gov ID
- NCT00956293
- Acronym / sponsor ID
- Senator / CRAD001ADE19
- Conditions
- Renal Transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated because the required sample size of 240-260 de novo senior renal transplant patients was not achieved within a reasonable time.
- Enrolment
- 207 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2009
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 11 Aug 2009 (estimated)
- Results
- Posted 12 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study wants to address whether a calcineurin-inhibitor (CNI)-free regimen six weeks after transplantation for Eurotransplant Senior Program (ESP) patients is as safe and well tolerated as standard treatment but optimizing immunosuppressive therapy with benefits in renal function, new-onset diabetes mellitus, cardiovascular risk, cancer and allograft nephropathy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Active comparator | Drug: Basiliximab, Drug: Enteric Coated Mycophenolic Acid (MPA), Drug: Cyclosporin A (CsA), Drug: CorticosteroidsDuring the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group continued with a CNI-based regimen of MPA and CsA. |
| Everolimus group | Experimental | Drug: Basiliximab, Drug: Enteric Coated Mycophenolic Acid (MPA), Drug: RAD001, Drug: Cyclosporin A (CsA), Drug: CorticosteroidsDuring the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group made a stepwise switch to a CNI-free regimen of everolimus and MPA. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- Patients receiving a primary kidney from a donor aged > 65 years
- In the Eurotransplant Senior Program
- Recipients of de novo cadaveric kidney transplants
Key exclusion criteria (10 listed)
- Multi-organ recipients (e.g., kidney and pancreas)
- Patients receiving a kidney from a non-heart beating donor
- Patients who are recipients of A-B-O incompatible transplants
- Patients with already existing antibodies against the HLA-type of the receiving transplant
- Patients who have received an investigational immunosuppressive drug within four weeks prior to study entry (Baseline visit 1)
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 |
|---|---|---|
| BasiliximabAlso: SimulectOn day 0, 2 hours prior to transplant and day 4 post-transplant, 20 mg x2 were given to all participants. Post randomization, 20mg at weeks 7 and 12 were given to the Everolimus group. | Drug | Control group, Everolimus group |
| Enteric Coated Mycophenolic Acid (MPA)Also: MyforticA loading dose regimen of 2880 mg/day during weeks 1 and 2 (pre-randomization) were given. During weeks 3 - 6 (pre-randomization), 2160 mg/day were given and during weeks 7 - 24, 1440 mg/day were given if tolerated. Dose reductions due to side effects were possible. | Drug | Control group, Everolimus group |
| RAD001Also: RAD001, CertcianUpon randomization, 3 mg (od) on Day 1, and 3 mg (1.5 mg every 12 hours) on Day 2 was given. Afterwards, the dosage was based on blood trough level (5 - 10 ng/mL). | Drug | Everolimus group |
| Cyclosporin A (CsA)Also: Sandimmun OptoralDosage was based according to blood level | Drug | Control group, Everolimus group |
| CorticosteroidsDosage was administered according to local standards and administration was optional as per clinical need and the Investigators' discretion. Steroid withdrawal occurred after week 2 (pre-randomization). | Drug | Control group, Everolimus group |
Primary outcome
Renal Function by Glomerular Filtration Rate (GFR) Via Cockcroft-Gault Method
Time frame: Month 6
The study was terminated prematurely and not powered for efficacy.
9 secondary outcomes
Renal Function by GFR Via Modification of Diet in Renal Diseases (MDRD) and Nankivell Method
Time frame: Month 6
Renal Function by Serum Creatinine
Time frame: Months 6, 12, 24, 36, 48 and 60
Biopsy Proven Acute Rejection (BPAR), Graft Loss and Death
Time frame: Months 6, 12, 24, 36, 48 and 60
Occurrence of Treatment Failures
Time frame: Month 6
Evolution of Renal Function (Creatinine Slope)
Time frame: Week 7, Month 6
CD25 Saturation on Lymphocytes
Time frame: Month 6
Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death
Time frame: Months 6, 12, 24, 36, 48 and 60
Renal Function by GFR Over Time
Time frame: Months 12, 24, 36, 48 and 60
Renal Function by Proteinuria
Time frame: Months12, 24, 36, 48 and 60
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31536556Brakemeier S, Arns W, Lehner F, Witzke O, Vonend O, Sommerer C, Muhlfeld A, Rath T, Schuhmann R, Zukunft B, Kroeger I, Porstner M, Budde K. Everolimus in de novo kidney transplant recipients participating in the Eurotransplant senior program: Results of a prospective randomized multicenter study (SENATOR). PLoS One. 2019 Sep 19;14(9):e0222730. doi: 10.1371/journal.pone.0222730. eCollection 2019.
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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
9 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 Basiliximab, Enteric Coated Mycophenolic Acid (MPA) and RAD001 in people with Renal Transplantation, run by Novartis Pharmaceuticals at 9 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 3 inclusion and 10 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 6 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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 12 May 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 by Glomerular Filtration Rate (GFR) Via Cockcroft-Gault Method (time frame: Month 6). 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 NCT00956293, 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 6 Jun 2014.