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

NCT00170846 | Completed Phase 4 Results DMC

• 1 other identifier: CRAD001A2413
• Study Type: interventional
• Target: 394
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Transplantation

Keywords

Renal transplantation, everolimus, calcineurin inhibitors, GFR

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months

Secondary Outcomes (1)

• Number of Participants With Safety Parameters

  24 months

Study Arms (3)

Group A: No RAD

ACTIVE COMPARATOR

Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids

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.

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.

Drug: Everolimus (RAD001); Drug: Calcineurin Inhibitors (CNI); Drug: Mycophenolate acid (MPA)/Azathioprine (AZA); Drug: Steroids

Interventions

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis

Basel, Switzerland

Location

MeSH Terms

Interventions

Everolimus; Calcineurin Inhibitors; Steroids

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis

  Novartis

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 15, 2005
• Study Start: February 1, 2005
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: January 27, 2015
• Results First Posted: May 2, 2011

Record last verified: 2011-03

Locations

CH (1)