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

• ClinicalTrials.gov Identifier: NCT00170846
• Recruitment Status: Completed
• First Posted: September 15, 2005
• Results First Posted: May 2, 2011
• Last Update Posted: January 27, 2015
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: September 9, 2005
• First Posted Date: September 15, 2005
• Results First Submitted Date: December 17, 2010
• Results First Posted Date: May 2, 2011
• Last Update Posted Date: January 27, 2015
• Study Start Date: February 2005
• Actual Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 31, 2011)

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.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: March 31, 2011)

Number of Participants With Safety Parameters [ Time Frame: 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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ASCERTAIN: Assessment of Everolimus in Addition to Calcineurin Inhibitor Reduction in the Maintenance of Renal Transplant Recipients
• Official Title: Assessment of Everolimus in Addition to Calcineurin Inhibitors Reduction in Maintenance Renal Transplant Recipients
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Renal Transplantation

Intervention

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

Study Arms

• Active Comparator: Group A: No RAD
  Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
  Interventions:

  • Drug: Calcineurin Inhibitors (CNI)
  • Drug: Mycophenolate acid (MPA)/Azathioprine (AZA)
  • Drug: Steroids
• Experimental: Group B : CNI Withdrawal
  Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus(RAD001) 4 mg initial daily dose.
  Interventions:

  • Drug: Everolimus (RAD001)
  • Drug: Mycophenolate acid (MPA)/Azathioprine (AZA)
  • Drug: Steroids
• Experimental: Group C: CNI Reduction
  Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 31, 2011): 394
• Original Enrollment: Not Provided
• Actual Study Completion Date: October 2009
• Actual Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT00170846
• Other Study ID Numbers: CRAD001A2413
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Not Provided
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Novartis
• Collaborators: Not Provided

Investigators

• Study Director: Novartis; Novartis

• PRS Account: Novartis
• Verification Date: March 2011