Kidney TransplantationPhase 3NCT00251004

Efficacy and Safety Study of Everolimus Plus Reduced Cyclosporine Versus Mycophenolic Acid Plus Cyclosporine in Kidney Transplant Recipients

A Phase 3 study testing Everolimus, Mycophenolic Acid (MPA) and Cyclosporine A (CsA) in people with Kidney Transplantation and Graft Rejection, run by Novartis at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study was to compare the safety and efficacy of three immunosuppressive treatment regimens following a kidney transplant. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Kidney Transplantation, Graft Rejection
What is being tested?: Everolimus, Mycophenolic Acid (MPA) and Cyclosporine A (CsA)
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 833 participants
Where: 1 siteUnited States
Study dates: Oct 2005to Oct 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 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and female patients of any race between 18 to 70 years old (inclusive)
Patients who gave written informed consent to participate in the study

Who cannot join

Recipients of multi-organ transplantation
Recipients of a primary cadaveric or primary non-human leucocyte antigen (HLA) identical living donor kidney transplantation.
Graft cold ischemia time greater than 40 hours.
Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

1 site in 1 country.

United States1 site

Novartis
East Hanover, New Jersey, 07936

Other trials in United States

About this study

Official title: Efficacy and Safety Study Comparing Concentration-controlled Everolimus in Two Doses (1.5 and 3.0 mg/Day Starting Doses) With Reduced Cyclosporine Versus 1.44 g Mycophenolic Acid (as Sodium Salt) With Standard Dose Cyclosporine in de Novo Renal Transplant Recipients

The purpose of this study was to compare the safety and efficacy of three immunosuppressive treatment regimens following a kidney transplant.

Conditions: Kidney Transplantation, Graft Rejection
Being tested: Everolimus, Mycophenolic Acid (MPA), Cyclosporine A (CsA), Basiliximab, Corticosteroids
Keywords: Renal transplantation, kidney, and organ transplant, Renal transplant rejection

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EverolimusDrug
Also called Certican, Zotress
oral, bis in diem/twice a day (bid)
Mycophenolic Acid (MPA)Drug
Also called Myfortic
2 oral capsules of mycophenolic acid 360mg administered bid
Cyclosporine A (CsA)Drug
Also called Neoral
CsA dose adjustments were based on CsA trough levels (C0).
BasiliximabDrug
Also called Simulect
All patients received two 20 mg doses of basiliximab administered intravenously. The first dose was to be given within 2 hours prior to transplant surgery and the second dose was to be administered on day 4, or each dose could have been administered according to local practice.
CorticosteroidsDrug
Oral corticosteroids were administered according to local practice during the trial. At the same center, all patients were to follow the same steroid administration protocol.

Study groups in NCT00251004
Study group	Role	What they receive
Low-dose Everolimus Group	Experimental	1.5 mg everolimus (one 0.75-mg tablet bis in diem/twice a day (bid)) + basiliximab + reduced-dose Cyclosporine A (CsA) ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. Receives: Drug: Everolimus; Drug: Cyclosporine A (CsA); Drug: Basiliximab; Drug: Corticosteroids
High-dose Everolimus Group	Experimental	3.0 mg everolimus (two 0.75-mg tablets bid) + basiliximab + reduced-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. Receives: Drug: Everolimus; Drug: Cyclosporine A (CsA); Drug: Basiliximab; Drug: Corticosteroids
Control Group	Active comparator	1.44 g Mycophenolic Acid (two 360-mg tablets bid) + basiliximab + standard-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a C0 value within the following range for the time of the study: starting at the day 5 visit: 200-300 ng/mL, starting at the month 2 visit and thereafter: 100-250 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy. Receives: Drug: Mycophenolic Acid (MPA); Drug: Cyclosporine A (CsA); Drug: Basiliximab; Drug: Corticosteroids

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Composite Efficacy Endpoints - 12 Month Analysis
The primary efficacy endpoint was the 12 month analysis of primary efficacy failure defined as a composite endpoint including treated biopsy proven acute rejection (BPAR), graft loss, death or loss to follow-up. A treated BPAR episode was defined as a biopsy graded IA, IB, IIA, IIB, or III that was treated with anti-rejection therapy. Graft loss was defined as the allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis as well as re-transplant.
Measured: 12 months
Non-inferiority Analysis on Percentage of Participants With Composite Efficacy Endpoints
The primary efficacy endpoint was the 12 month analysis of primary efficacy failure defined as a composite endpoint including treated biopsy proven acute rejection (BPAR), graft loss, death or loss to follow-up. In the definition of composite efficacy failure, loss to follow-up includes patients who did not experience treated BPAR, graft loss or death on or after day 1 and whose last day of contact was prior to day 316, the start day of the 12 month visit window.
Measured: 12 months

Secondary outcomes (2)

Percentage of Participants With the Composite Incidence of Graft Loss, Death or Loss to Follow up at 12 Months Post-transplantation
Graft loss was defined as graft loss (the allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis) and re-transplant.
A loss to follow-up patient in the composite endpoint of graft loss, death or loss to follow-up (the main secondary efficacy endpoint) was a patient who did not experience graft loss or death from day 1 and whose last day of contact was prior to study day 316.
Measured: 12 months
Non-inferiority Analysis of Renal Function, Calculated by Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula
Modification of Diet in Renal Disease (MDRD) formula is:
GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where
- C is the serum concentration of creatinine [mg/dL],
- A is patient age at sample collection date [years],
- G=0.742 when gender is female, otherwise G=1,
- R=1.21 when race is black, otherwise R=1
Measured: at 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2005Oct 2009

First posted9 Nov 2005 (estimated)
Study startOct 2005
Primary completionAug 2009
Study completionOct 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.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Kidney TransplantationStudies of the same condition, open and under way.
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: 833 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00251004
Sponsor's protocol ID: CRAD001A2309
Status last verified: Apr 2011
First submitted: 7 Nov 2005
Last updated: 10 May 2011
Results posted: Yes, on ClinicalTrials.gov

Publications

Wajih Z, Karpe KM, Walters GD. Interventions for BK virus infection in kidney transplant recipients. Cochrane Database Syst Rev. 2024 Oct 9;10(10):CD013344. doi: 10.1002/14651858.CD013344.pub2.
PubMed 39382091
Cibrik D, Silva HT Jr, Vathsala A, Lackova E, Cornu-Artis C, Walker RG, Wang Z, Zibari GB, Shihab F, Kim YS. Randomized trial of everolimus-facilitated calcineurin inhibitor minimization over 24 months in renal transplantation. Transplantation. 2013 Apr 15;95(7):933-42. doi: 10.1097/TP.0b013e3182848e03.
PubMed 23422495
Shihab FS, Cibrik D, Chan L, Kim YS, Carmellini M, Walker R, Zibari G, Pattison J, Cornu-Artis C, Wang Z, Tedesco-Silva H Jr. Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine. Clin Transplant. 2013 Mar-Apr;27(2):217-26. doi: 10.1111/ctr.12045. Epub 2012 Dec 12.
PubMed 23230975

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruitingEarly Phase 1
Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients
Kidney Transplant Recipient
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney

All Kidney Transplantation trials

Study at a glance

From the registry record, last updated by the sponsor on 10 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy and Safety Study Comparing Concentration-controlled Everolimus in Two Doses (1.5 and 3.0 mg/Day Starting Doses) With Reduced Cyclosporine Versus 1.44 g Mycophenolic Acid (as Sodium Salt) With Standard Dose Cyclosporine in de Novo Renal Transplant Recipients
ClinicalTrials.gov ID: NCT00251004
Acronym / sponsor ID: CRAD001A2309
Conditions: Kidney Transplantation, Graft Rejection
Keywords: Renal transplantation, kidney, and organ transplant, Renal transplant rejection
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 833 participants (actual)
Lead sponsor: NovartisIndustry (pharma, biotech, devices)
Study start: Oct 2005
Primary completion: Aug 2009 (actual)
Study completion: Oct 2009 (actual)
First posted: 9 Nov 2005 (estimated)
Results: Posted 10 May 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 compare the safety and efficacy of three immunosuppressive treatment regimens following a kidney transplant.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Low-dose Everolimus Group	Experimental	Drug: Everolimus, Drug: Cyclosporine A (CsA), Drug: Basiliximab, Drug: Corticosteroids1.5 mg everolimus (one 0.75-mg tablet bis in diem/twice a day (bid)) + basiliximab + reduced-dose Cyclosporine A (CsA) ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy.
High-dose Everolimus Group	Experimental	Drug: Everolimus, Drug: Cyclosporine A (CsA), Drug: Basiliximab, Drug: Corticosteroids3.0 mg everolimus (two 0.75-mg tablets bid) + basiliximab + reduced-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a trough (C0) value within the pre-specified target ranges: starting at the day 5 visit: 100-200 ng/mL, starting at the month 2 visit: 75-150 ng/mL, starting at the month 4 visit: 50-100 ng/mL and starting at the month 6 visit: 25-50 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy.
Control Group	Active comparator	Drug: Mycophenolic Acid (MPA), Drug: Cyclosporine A (CsA), Drug: Basiliximab, Drug: Corticosteroids1.44 g Mycophenolic Acid (two 360-mg tablets bid) + basiliximab + standard-dose CsA ± corticosteroids. The CsA dose was adjusted to attain a C0 value within the following range for the time of the study: starting at the day 5 visit: 200-300 ng/mL, starting at the month 2 visit and thereafter: 100-250 ng/mL. Patients received their first dose of basiliximab within 2 hours prior to transplant surgery and on day 4 post-transplant or according to local practice. Corticosteroids were administered according to local therapy.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Male and female patients of any race between 18 to 70 years old (inclusive)
Patients who gave written informed consent to participate in the study

Key exclusion criteria (4 listed)

Recipients of multi-organ transplantation
Recipients of a primary cadaveric or primary non-human leucocyte antigen (HLA) identical living donor kidney transplantation.
Graft cold ischemia time greater than 40 hours.
Other protocol-defined inclusion/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: Certican, Zotressoral, bis in diem/twice a day (bid)	Drug	High-dose Everolimus Group, Low-dose Everolimus Group
Mycophenolic Acid (MPA)Also: Myfortic2 oral capsules of mycophenolic acid 360mg administered bid	Drug	Control Group
Cyclosporine A (CsA)Also: NeoralCsA dose adjustments were based on CsA trough levels (C0).	Drug	Control Group, High-dose Everolimus Group, Low-dose Everolimus Group
BasiliximabAlso: SimulectAll patients received two 20 mg doses of basiliximab administered intravenously. The first dose was to be given within 2 hours prior to transplant surgery and the second dose was to be administered on day 4, or each dose could have been administered according to local practice.	Drug	Control Group, High-dose Everolimus Group, Low-dose Everolimus Group
CorticosteroidsOral corticosteroids were administered according to local practice during the trial. At the same center, all patients were to follow the same steroid administration protocol.	Drug	Control Group, High-dose Everolimus Group, Low-dose Everolimus Group

Primary outcome

Number of Participants With Composite Efficacy Endpoints - 12 Month Analysis
Time frame: 12 months
The primary efficacy endpoint was the 12 month analysis of primary efficacy failure defined as a composite endpoint including treated biopsy proven acute rejection (BPAR), graft loss, death or loss to follow-up. A treated BPAR episode was defined as a biopsy graded IA, IB, IIA, IIB, or III that was treated with anti-rejection therapy. Graft loss was defined as the allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis as well as re-transplant.
Non-inferiority Analysis on Percentage of Participants With Composite Efficacy Endpoints
Time frame: 12 months
The primary efficacy endpoint was the 12 month analysis of primary efficacy failure defined as a composite endpoint including treated biopsy proven acute rejection (BPAR), graft loss, death or loss to follow-up. In the definition of composite efficacy failure, loss to follow-up includes patients who did not experience treated BPAR, graft loss or death on or after day 1 and whose last day of contact was prior to day 316, the start day of the 12 month visit window.

2 secondary outcomes

Percentage of Participants With the Composite Incidence of Graft Loss, Death or Loss to Follow up at 12 Months Post-transplantation
Time frame: 12 months
Non-inferiority Analysis of Renal Function, Calculated by Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula
Time frame: at 12 months

Results and safety

Results posted to the registry on 10 May 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Low-dose Everolimus Group	277	232
High-dose Everolimus Group	279	238
Control Group	277	246

Primary outcome: Number of Participants With Composite Efficacy Endpoints - 12 Month Analysis

Time frame: 12 months. Number. Unit: Participants

Measure	Low-dose Everolimus Group n = 277	High-dose Everolimus Group n = 279	Control Group n = 277
Composite Endpoint (n)	75	60	70
--Death	8	9	6
--Graft Loss	13	13	9
--Treated BPAR	48	38	50
--Lost to follow up	12	6	9

Population analysed: Intention-to-treat (ITT) population

Primary outcome: Non-inferiority Analysis on Percentage of Participants With Composite Efficacy Endpoints

Time frame: 12 months. Number. Unit: Percentage of Participants

Measure	Low-dose Everolimus Group n = 277	High-dose Everolimus Group n = 279	Control Group n = 277
Value	27.1	21.5	25.3

Low-dose Everolimus Group vs Control Group: Difference in percentage: 1.8 (95% CI -5.5 to 9.1), p = 0.014, Z - test
High-dose Everolimus Group vs Control Group: Difference in percentage: -3.8 (95% CI -10.8 to 3.3), p <0.001, Z-test

Population analysed: Intention-to-treat population

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: At 24 month. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Low-dose Everolimus Group	176 of 274 (64.2%)	268 of 274 (97.8%)	Not reported
High-dose Everolimus Group	193 of 278 (69.4%)	272 of 278 (97.8%)	Not reported
Control Group	168 of 273 (61.5%)	264 of 273 (96.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39382091Wajih Z, Karpe KM, Walters GD. Interventions for BK virus infection in kidney transplant recipients. Cochrane Database Syst Rev. 2024 Oct 9;10(10):CD013344. doi: 10.1002/14651858.CD013344.pub2.
Derived from this study: PubMed 23422495Cibrik D, Silva HT Jr, Vathsala A, Lackova E, Cornu-Artis C, Walker RG, Wang Z, Zibari GB, Shihab F, Kim YS. Randomized trial of everolimus-facilitated calcineurin inhibitor minimization over 24 months in renal transplantation. Transplantation. 2013 Apr 15;95(7):933-42. doi: 10.1097/TP.0b013e3182848e03.
Derived from this study: PubMed 23230975Shihab FS, Cibrik D, Chan L, Kim YS, Carmellini M, Walker R, Zibari G, Pattison J, Cornu-Artis C, Wang Z, Tedesco-Silva H Jr. Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine. Clin Transplant. 2013 Mar-Apr;27(2):217-26. doi: 10.1111/ctr.12045. Epub 2012 Dec 12.

Related trials for Kidney Transplantation

Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruitingEarly Phase 1
Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients
Kidney Transplant Recipient
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney

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 study director

Novartis

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Everolimus, Mycophenolic Acid (MPA) and Cyclosporine A (CsA) in people with Kidney Transplantation and Graft Rejection, run by Novartis at 1 site in United States.

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 2 inclusion and 4 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 10 May 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 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 10 May 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 Composite Efficacy Endpoints - 12 Month Analysis (time frame: 12 months). 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?

On the ClinicalTrials.gov record for NCT00251004, which also lists 3 linked publications.

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 10 May 2011.