Renal TransplantationPhase 4NCT00170846

ASCERTAIN: Assessment of Everolimus in Addition to Calcineurin Inhibitor Reduction in the Maintenance of Renal Transplant Recipients

A Phase 4 study testing Everolimus (RAD001), Calcineurin Inhibitors (CNI) and Mycophenolate acid (MPA)/Azathioprine (AZA) in people with Renal Transplantation, run by Novartis Pharmaceuticals at 1 site in Switzerland.

Completed

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

Official record

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Trial summary

The study is designed to evaluate whether the initiation of everolimus together with the reduction or discontinuation of calcineurin inhibitors (CNIs) will improve graft function in the maintenance of renal transplant recipients with renal impairment by reducing the progression of chronic allograft nephropathy. 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 (RAD001), Calcineurin Inhibitors (CNI) and Mycophenolate acid (MPA)/Azathioprine (AZA)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 394 participants
Where: 1 siteSwitzerland
Study dates: Feb 2005to Oct 2009
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

Male or female patient at least 18 years of age.
Patient who has undergone a primary or secondary renal transplant 12-96 months ago from a living related or unrelated donor or a cadaveric donor.
Patient receiving cyclosporine microemulsion with a C2-h level ≥ 400 ng/mL or tacrolimus with a C0-h level ≥ 4 ng/mL with or without mycophenolic acid or azathioprine plus or minus steroids.
The immunosuppressive regimen must remain unchanged within the last 3 months.
Patient with renal impairment defined as GFR between 30 and 70 mL/min/1.73 m^2 by Cockcroft-Gault formula.

Who cannot join

Patient who is recipient of multiple organ transplants.
Patient with protein/creatinine ratio ≥ 150 (mg/mmol).
Patient with a treated acute rejection episode within the last 3 months.
Patient with any past or present BK-polyomavirus nephropathy.
Patient with de novo or recurrent glomerular nephritis.
Other protocol defined inclusion/exclusion criteria may apply.

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

Novartis
Basel

Other trials in Switzerland

About this study

Official title: Assessment of Everolimus in Addition to Calcineurin Inhibitors Reduction in Maintenance Renal Transplant Recipients

Conditions: Renal Transplantation
Being tested: Everolimus (RAD001), Calcineurin Inhibitors (CNI), Mycophenolate acid (MPA)/Azathioprine (AZA), Steroids
Keywords: Renal transplantation, everolimus, calcineurin inhibitors, GFR

What participants receive

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

Everolimus (RAD001)Drug
Calcineurin Inhibitors (CNI)Drug
Mycophenolate acid (MPA)/Azathioprine (AZA)Drug
SteroidsDrug

Study groups in NCT00170846
Study group	Role	What they receive
Group A: No RAD	Active comparator	Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids Receives: Drug: Calcineurin Inhibitors (CNI); Drug: Mycophenolate acid (MPA)/Azathioprine (AZA); Drug: Steroids
Group B : CNI Withdrawal	Experimental	Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus(RAD001) 4 mg initial daily dose. Receives: Drug: Everolimus (RAD001); Drug: Mycophenolate acid (MPA)/Azathioprine (AZA); Drug: Steroids
Group C: CNI Reduction	Experimental	Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose. Receives: Drug: Everolimus (RAD001); Drug: Calcineurin Inhibitors (CNI); Drug: Mycophenolate acid (MPA)/Azathioprine (AZA); Drug: Steroids

What is being measured

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

Renal Function Assessed by Measured GFR (mGFR)
The acceptable methods for GFR measurement were Chromium 51-Ethylenediaminetetra acetic acid (Cr-EDTA), Technetium 99-Diethylenetriaminepentacetic acid (Tc-DTPA), Iohexol clearance Inuline clearance and Iothalamate clearance. The method should have been consistent for a given patient at every time point.
Measured: 24 months

Secondary outcomes (1)

Number of Participants With Safety Parameters
The selected safety parameters (such as hypertension, hyperlipidemia, diabetes mellitus, anemia, malignancies ) were derived based on adverse events preferred terms defined in the analysis plan.
Measured: 24 months

Timeline

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

Feb 2005Oct 2009

First posted15 Sep 2005 (estimated)
Study startFeb 2005
Primary completionOct 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.
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: 394 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00170846
Sponsor's protocol ID: CRAD001A2413
Status last verified: Mar 2011
First submitted: 9 Sep 2005
Last updated: 27 Jan 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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

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All Renal Transplantation trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Assessment of Everolimus in Addition to Calcineurin Inhibitors Reduction in Maintenance Renal Transplant Recipients
ClinicalTrials.gov ID: NCT00170846
Acronym / sponsor ID: CRAD001A2413
Conditions: Renal Transplantation
Keywords: Renal transplantation, everolimus, calcineurin inhibitors, GFR
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 394 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Feb 2005
Primary completion: Oct 2009 (actual)
Study completion: Oct 2009 (actual)
First posted: 15 Sep 2005 (estimated)
Results: Posted 2 May 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

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

Arm	Type	Receives
Group A: No RAD	Active comparator	Drug: Calcineurin Inhibitors (CNI), Drug: Mycophenolate acid (MPA)/Azathioprine (AZA), Drug: SteroidsCalcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group B : CNI Withdrawal	Experimental	Drug: Everolimus (RAD001), Drug: Mycophenolate acid (MPA)/Azathioprine (AZA), Drug: SteroidsInitiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus(RAD001) 4 mg initial daily dose.
Group C: CNI Reduction	Experimental	Drug: Everolimus (RAD001), Drug: Calcineurin Inhibitors (CNI), Drug: Mycophenolate acid (MPA)/Azathioprine (AZA), Drug: SteroidsInitiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.

Who may qualify

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

Key inclusion criteria (5 listed)

Male or female patient at least 18 years of age.
Patient who has undergone a primary or secondary renal transplant 12-96 months ago from a living related or unrelated donor or a cadaveric donor.
Patient receiving cyclosporine microemulsion with a C2-h level ≥ 400 ng/mL or tacrolimus with a C0-h level ≥ 4 ng/mL with or without mycophenolic acid or azathioprine plus or minus steroids.
The immunosuppressive regimen must remain unchanged within the last 3 months.
Patient with renal impairment defined as GFR between 30 and 70 mL/min/1.73 m^2 by Cockcroft-Gault formula.

Key exclusion criteria (6 listed)

Patient who is recipient of multiple organ transplants.
Patient with protein/creatinine ratio ≥ 150 (mg/mmol).
Patient with a treated acute rejection episode within the last 3 months.
Patient with any past or present BK-polyomavirus nephropathy.
Patient with de novo or recurrent glomerular nephritis.

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 (RAD001)	Drug	Group B : CNI Withdrawal, Group C: CNI Reduction
Calcineurin Inhibitors (CNI)	Drug	Group A: No RAD, Group C: CNI Reduction
Mycophenolate acid (MPA)/Azathioprine (AZA)	Drug	Group A: No RAD, Group B : CNI Withdrawal, Group C: CNI Reduction
Steroids	Drug	Group A: No RAD, Group B : CNI Withdrawal, Group C: CNI Reduction

Primary outcome

Renal Function Assessed by Measured GFR (mGFR)
Time frame: 24 months
The acceptable methods for GFR measurement were Chromium 51-Ethylenediaminetetra acetic acid (Cr-EDTA), Technetium 99-Diethylenetriaminepentacetic acid (Tc-DTPA), Iohexol clearance Inuline clearance and Iothalamate clearance. The method should have been consistent for a given patient at every time point.

1 secondary outcome

Number of Participants With Safety Parameters
Time frame: 24 months

Results and safety

Results posted to the registry on 2 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
Group A: No RAD	123	112
Group B : CNI Withdrawal	127	108
Group C: CNI Reduction	144	131

Primary outcome: Renal Function Assessed by Measured GFR (mGFR)

Time frame: 24 months. Mean (Standard Deviation). Unit: mL/min/1.73m^2

Measure	Group A: No RAD n = 103	Group B : CNI Withdrawal n = 94	Group C: CNI Reduction n = 109
Value	46.02 (20.358)	48.00 (22.033)	46.60 (21.079)

Group A: No RAD vs Group B : CNI Withdrawal: Difference in LS means: 1.1241 (95% CI -3.5077 to 5.7559), p = 0.6332, ANCOVA
Group A: No RAD vs Group C: CNI Reduction: Difference in LS means: 0.5933 (95% CI -3.8815 to 5.0682), p = 0.7943, ANCOVA

Population analysed: The modified ITT population included all ITT patients who had mGFR or calculated GFR (cGFR) at Month 24 based on all values including those collected after discontinuation of study medication.

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group A: No RAD	52 of 123 (42.3%)	97 of 123 (78.9%)	Not reported
Group B : CNI Withdrawal	72 of 127 (56.7%)	116 of 127 (91.3%)	Not reported
Group C: CNI Reduction	78 of 144 (54.2%)	126 of 144 (87.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Renal 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
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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 study director

Novartis

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

Questions about this trial

What is this clinical trial studying?

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 5 inclusion and 6 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 27 Jan 2015. 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 Switzerland. 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 2 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?

Renal Function Assessed by Measured GFR (mGFR) (time frame: 24 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 NCT00170846.

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 27 Jan 2015.