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

Phase 4

Completed

• Conditions: Renal Transplantation
• Interventions: Drug: Everolimus (RAD001); Drug: Calcineurin Inhibitors (CNI); Drug: Mycophenolate acid (MPA)/Azathioprine (AZA); Drug: Steroids

• Registration Number: NCT00170846
• Lead Sponsor: Novartis Pharmaceuticals

Brief 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. The development of atherosclerosis in the native arteries of the patients will also be explored.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-02
• Study First Submitted: 2005-09-09
• Study First Submitted QC: 2005-09-09
• Study First Posted: 2005-09-15
• Primary Completion: 2009-10
• Study Completion: 2009-10
• Results First Submitted: 2010-12-17
• Status Verified: 2011-03
• Results First Submitted QC: 2011-03-31
• Results First Posted: 2011-05-02
• Last Update Submitted: 2015-01-15
• Last Update Posted: 2015-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 394

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group C: CNI Reduction	Everolimus (RAD001)	Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Group C: CNI Reduction	Mycophenolate acid (MPA)/Azathioprine (AZA)	Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Group A: No RAD	Mycophenolate acid (MPA)/Azathioprine (AZA)	Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group B : CNI Withdrawal	Steroids	Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus(RAD001) 4 mg initial daily dose.
Group C: CNI Reduction	Steroids	Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Group A: No RAD	Steroids	Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group B : CNI Withdrawal	Everolimus (RAD001)	Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus(RAD001) 4 mg initial daily dose.
Group B : CNI Withdrawal	Mycophenolate acid (MPA)/Azathioprine (AZA)	Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus(RAD001) 4 mg initial daily dose.
Group A: No RAD	Calcineurin Inhibitors (CNI)	Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group C: CNI Reduction	Calcineurin Inhibitors (CNI)	Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.

Primary Outcome Measures

Name	Time	Method
Renal Function Assessed by Measured GFR (mGFR)	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Safety Parameters	24 months	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.

Trial Locations

Locations (1)

Novartis; 🇨🇭 Basel, Switzerland