Transplantation InfectionPhase 3EVERESTNCT01276457
Everolimus in Combination With Cyclosporine Microemulsion in de Novo Renal Transplant Recipients
A Phase 3 study testing Everolimus 0.25 and 0.75 mg tablets, Cyclosporine very low dose (150-300 ng/mL) microemulsion and Cyclosporine low dose (350-500 ng/mL) microemulsion in people with Transplantation Infection, run by Novartis Pharmaceuticals.
Trial summary
The purpose of this study was to allow the continuation of everolimus treatment in patients who have completed the core study (NCT00170885) and to collect long-term safety, tolerability, and efficacy data in a group of patients treated with the upper everolimus target levels plus very low dose cyclosporin in… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Transplantation Infection
- What is being tested?
- Everolimus 0.25 and 0.75 mg tablets, Cyclosporine very low dose (150-300 ng/mL) microemulsion and Cyclosporine low dose (350-500 ng/mL) microemulsion
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 223 participants
- Where
- No sites listed yet
- Study dates
- May 2006to Feb 2009
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with functioning graft who had completed the 6-month treatment period of core study
- Patients who were receiving treatment with either everolimus and cyclosporin at the end of the core study
- Patients who signed the informed consent of the present study extension
Who cannot join
- Women who were pregnant, lactating or who wished to became pregnant.
- Other protocol-defined inclusion/exclusion criteria applied to the study.
About this study
Official title: An 18 Month Extension to the Multicenter, Randomized, Open-label Trial (NCT00170885) to Evaluate the Safety, Tolerability, and Efficacy of Two Regimens of Everolimus Plus Cyclosporine Microemulsion, Given According to Different Blood Target Levels, in de Novo Renal Transplant Recipients
The purpose of this study was to allow the continuation of everolimus treatment in patients who have completed the core study (NCT00170885) and to collect long-term safety, tolerability, and efficacy data in a group of patients treated with the upper everolimus target levels plus very low dose cyclosporin in comparison with the standard everolimus target levels plus low dose cyclosporin in patients with renal transplantation.
- Conditions
- Transplantation Infection
- Being tested
- Everolimus 0.25 and 0.75 mg tablets, Cyclosporine very low dose (150-300 ng/mL) microemulsion, Cyclosporine low dose (350-500 ng/mL) microemulsion
- Keywords
- immunosuppression, kidney transplantation, everolimus, safety
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus 0.25 and 0.75 mg tabletsDrug
The dose of everolimus for each patient was adjusted to achieve the target everolimus blood level range. Everolimus blood trough level was measured 5 days after any dose adjustment to verify that the blood level was within the desired target level range.
Cyclosporine very low dose (150-300 ng/mL) microemulsionDrug
Also called Neoral
The dose of cyclosporine for each patient was adjusted to achieve the target cyclosporine blood level. Cyclosporine dose adjustments were based on drug blood level determined from whole blood samples taken 2 hours (± 10 min) after the morning dose.
Cyclosporine low dose (350-500 ng/mL) microemulsionDrug
Also called Neoral
The dose of cyclosporine for each patient was adjusted to achieve the target cyclosporine blood level. Cyclosporine dose adjustments were based on drug blood level determined from whole blood samples taken 2 hours (± 10 min) after the morning dose.
| Study group | Role | What they receive |
|---|---|---|
| Upper everolimus blood target + very low dose cyclosporine | Experimental | Patients received everolimus orally twice daily at a dose that was adjusted to achieve a drug blood trough level in the range of 8-12 ng/mL. Patients also received a very low dose of cyclosporine (150-300 ng/mL) orally twice daily that was adjusted to maintain a drug blood level of 200 ng/mL 2 hours after the morning dose. Both drugs were taken in the morning and again 12 hours later. The drugs were taken consistently either before, during, or after meals. No grapefruit or grapefruit juice was allowed throughout the study. Receives: Drug: Everolimus 0.25 and 0.75 mg tablets; Drug: Cyclosporine very low dose (150-300 ng/mL) microemulsion |
| Standard everolimus blood target + low dose cyclosporine | Active comparator | Patients received everolimus orally twice daily at a dose that was adjusted to achieve a drug blood trough level in the range of 3-8 ng/mL. Patients also received a low dose of cyclosporine (350-500 ng/mL) orally twice daily that was adjusted to maintain a drug blood level of 400 ng/mL 2 hours after the morning dose. Both drugs were taken in the morning and again 12 hours later. The drugs were taken consistently either before, during, or after meals. No grapefruit or grapefruit juice was allowed throughout the study. Receives: Drug: Everolimus 0.25 and 0.75 mg tablets; Drug: Cyclosporine low dose (350-500 ng/mL) microemulsion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Biopsy-proven Acute Rejection
A graft core biopsy was performed on all suspected acute rejection episodes within 48 hours. Biopsies were read by the local pathologist according to the 1997 Banff criteria. A biopsy-proven acute rejection was be defined as a biopsy graded IA, IB, IIA, IIB, or III.
Measured: Baseline to end of study (Month 24)
Renal Function Assessed by Creatinine Clearance
Renal function was assessed by measuring serum creatinine and by computing creatinine clearance using the formula of Cockcroft-Gault.
Measured: Month 12, Month 18, and Month 24
Secondary outcomes (2)
Number of Participants Who Died, Number of Participants Who Lost Their Graft, and Number of Participants Who Died or Lost Their Graft
A participant lost his graft if he/she started dialysis and was not able to subsequently be removed from dialysis or underwent graft nephrectomy.
Measured: Baseline to end of study (Month 24)
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Deaths
Safety was assessed using reports of adverse events of all participants in this study. Serious adverse events are those events that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.
Measured: Baseline to end of study (Month 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2011 (estimated)
- Study startMay 2006
- Primary completionFeb 2009
- Study completionFeb 2009
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 Transplantation InfectionStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 223 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01276457
- Sponsor's protocol ID
- CRAD001AIT02E1
- Acronym
- EVEREST
- Status last verified
- May 2011
- First submitted
- 12 Jan 2011
- Last updated
- 20 May 2011
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An 18 Month Extension to the Multicenter, Randomized, Open-label Trial (NCT00170885) to Evaluate the Safety, Tolerability, and Efficacy of Two Regimens of Everolimus Plus Cyclosporine Microemulsion, Given According to Different Blood Target Levels, in de Novo Renal Transplant Recipients
- ClinicalTrials.gov ID
- NCT01276457
- Acronym / sponsor ID
- EVEREST / CRAD001AIT02E1
- Conditions
- Transplantation Infection
- Keywords
- immunosuppression, kidney transplantation, everolimus, safety
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 223 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2006
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 13 Jan 2011 (estimated)
- Results
- Posted 19 Apr 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to allow the continuation of everolimus treatment in patients who have completed the core study (NCT00170885) and to collect long-term safety, tolerability, and efficacy data in a group of patients treated with the upper everolimus target levels plus very low dose cyclosporin in comparison with the standard everolimus target levels plus low dose cyclosporin in patients with renal transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Upper everolimus blood target + very low dose cyclosporine | Experimental | Drug: Everolimus 0.25 and 0.75 mg tablets, Drug: Cyclosporine very low dose (150-300 ng/mL) microemulsionPatients received everolimus orally twice daily at a dose that was adjusted to achieve a drug blood trough level in the range of 8-12 ng/mL. Patients also received a very low dose of cyclosporine (150-300 ng/mL) orally twice daily that was adjusted to maintain a drug blood level of 200 ng/mL 2 hours after the morning dose. Both drugs were taken in the morning and again 12 hours later. The drugs were taken consistently either before, during, or after meals. No grapefruit or grapefruit juice was allowed throughout the study. |
| Standard everolimus blood target + low dose cyclosporine | Active comparator | Drug: Everolimus 0.25 and 0.75 mg tablets, Drug: Cyclosporine low dose (350-500 ng/mL) microemulsionPatients received everolimus orally twice daily at a dose that was adjusted to achieve a drug blood trough level in the range of 3-8 ng/mL. Patients also received a low dose of cyclosporine (350-500 ng/mL) orally twice daily that was adjusted to maintain a drug blood level of 400 ng/mL 2 hours after the morning dose. Both drugs were taken in the morning and again 12 hours later. The drugs were taken consistently either before, during, or after meals. No grapefruit or grapefruit juice was allowed throughout the study. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with functioning graft who had completed the 6-month treatment period of core study
- Patients who were receiving treatment with either everolimus and cyclosporin at the end of the core study
- Patients who signed the informed consent of the present study extension
Key exclusion criteria (2 listed)
- Women who were pregnant, lactating or who wished to became pregnant.
- Other protocol-defined inclusion/exclusion criteria applied to the study.
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 |
|---|---|---|
| Everolimus 0.25 and 0.75 mg tabletsThe dose of everolimus for each patient was adjusted to achieve the target everolimus blood level range. Everolimus blood trough level was measured 5 days after any dose adjustment to verify that the blood level was within the desired target level range. | Drug | Standard everolimus blood target + low dose cyclosporine, Upper everolimus blood target + very low dose cyclosporine |
| Cyclosporine very low dose (150-300 ng/mL) microemulsionAlso: NeoralThe dose of cyclosporine for each patient was adjusted to achieve the target cyclosporine blood level. Cyclosporine dose adjustments were based on drug blood level determined from whole blood samples taken 2 hours (± 10 min) after the morning dose. | Drug | Upper everolimus blood target + very low dose cyclosporine |
| Cyclosporine low dose (350-500 ng/mL) microemulsionAlso: NeoralThe dose of cyclosporine for each patient was adjusted to achieve the target cyclosporine blood level. Cyclosporine dose adjustments were based on drug blood level determined from whole blood samples taken 2 hours (± 10 min) after the morning dose. | Drug | Standard everolimus blood target + low dose cyclosporine |
Primary outcome
Number of Participants With Biopsy-proven Acute Rejection
Time frame: Baseline to end of study (Month 24)
A graft core biopsy was performed on all suspected acute rejection episodes within 48 hours. Biopsies were read by the local pathologist according to the 1997 Banff criteria. A biopsy-proven acute rejection was be defined as a biopsy graded IA, IB, IIA, IIB, or III.
Renal Function Assessed by Creatinine Clearance
Time frame: Month 12, Month 18, and Month 24
Renal function was assessed by measuring serum creatinine and by computing creatinine clearance using the formula of Cockcroft-Gault.
2 secondary outcomes
Number of Participants Who Died, Number of Participants Who Lost Their Graft, and Number of Participants Who Died or Lost Their Graft
Time frame: Baseline to end of study (Month 24)
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Deaths
Time frame: Baseline to end of study (Month 24)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2011.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Everolimus 0.25 and 0.75 mg tablets, Cyclosporine very low dose (150-300 ng/mL) microemulsion and Cyclosporine low dose (350-500 ng/mL) microemulsion in people with Transplantation Infection, run by Novartis Pharmaceuticals.
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 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: finished, as of the sponsor's last update on 20 May 2011. Status can change between updates, so confirm with the study contact before making plans.
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 19 Apr 2011). 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?
Number of Participants With Biopsy-proven Acute Rejection (time frame: Baseline to end of study (Month 24)). The study lists 2 primary outcomes in all. 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 20 May 2011.