Efficacy, Safety and Evolution of Cardiovascular Parameters in Renal Transplant Recipients

Renal Transplantation Clinical Trial

— ELEVATE  

Official title:

A 24-month, Multi-center, Open-label, Randomized, Controlled Trial to Investigate Efficacy, Safety and Evolution of Cardiovascular Parameters in de Novo Renal Transplant Recipients After Early Calcineurin Inhibitor to Everolimus Conversion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01114529
• Other study ID #: CRAD001A2429
• Secondary ID: 2009-015918-22
• Status: Completed
• Phase: Phase 3
• First received: April 27, 2010
• Last updated: October 5, 2015
• Start date: August 2010
• Est. completion date: October 2014

Study information

• Verified date: October 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether an early Calcineurin Inhibitor (CNI) to everolimus conversion at 10-14 weeks post transplantation improves renal allograft function without compromising efficacy compared to standard CNI treatment in de novo renal allograft recipients. In addition, the study is designed to evaluate the impact of a CNI-free regimen on evolution of cardiovascular parameters in de novo renal allograft recipients

Recruitment information / eligibility

• Status: Completed
• Enrollment: 825
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria at Baseline:

• Male or female renal allograft recipients at least 18 years old.

• Written informed consent.

• Patient receiving a primary or secondary kidney transplant from a cadaveric or living unrelated-/related donor.

• Cold ischemia time (CIT) < 24 hours.

• Negative pregnancy test for female patients.

Inclusion Criteria at Randomization:

• Patients on CNI (TAC or CsA) + Myfortic + steroids.

• Serum creatinine < 2.8 mg/dL (250 µmol/L) and an actual eGFR (MDRD4) = 25 mL/min/1.73m exp2 (without renal replacement therapy).

Exclusion Criteria at Baseline:

• Patients fulfilling any of the following criteria are not eligible for inclusion in this study:

• Recipient of multiple organ transplants.

• Recipient of ABO incompatible allograft or a positive cross-match.

• Panel Reactive Antibodies (PRA) level = 30 %.

• Positive test for human immunodeficiency virus (HIV).

• Patient receiving an allograft from a Hepatitis B surface Antigen (HBsAg) or a Hepatitis C Virus (HCV) positive donor.

• HBsAg and/or a HCV positive patient with evidence of elevated LFTs (ALT/AST levels = 2.5 times ULN).

• Severe restrictive or obstructive pulmonary disorders.

• Patient with severe allergy requiring acute or chronic treatment or hypersensitivity to any of the study drugs or similar drugs.

• Severe hypercholesterolemia or hypertriglyceridemia.

• Low platelet count.

• Low white blood cell count.

• History of malignancy of any organ system

Exclusion Criteria at Randomization:

• Graft loss.

• Patient on renal replacement therapy.

• Patient who experienced severe humoral and/or cellular rejection (BANFF = IIb).

• Patient with = 2 episodes of AR or an AR episode that needed antibody treatment.

• Patient with ongoing or currently treated AR (2 weeks prior to randomization).

• Proteinuria > 1 g/day.

• Patients with recurrence of Focal Segmental Glomerulosclerosis (FSGS).

• Low platelet count; Low white blood cell count; Low absolute neutrophil count; Low hemoglobin.

• Severe liver disease.

• Systemic infection requiring continued therapy that would interfere with the objectives of the study.

• Severe hypercholesterolemia or hypertriglyceridemia.

• Patients with ongoing wound healing problems, clinically significant infection requiring continued therapy.

• Presence of intractable immunosuppressant complications or side effects.

• Patients on anticoagulants that prevents renal allograft biopsy.

• Use of prohibited medication.

• Use of immunosuppressive agents not utilized in the protocol.

• Pregnant or nursing (lactating) women.

• Women of child-bearing potential not using a highly effective method of birth control.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

Drug:
• Everolimus
Early CNI to everolimus conversion
• Prograf or Neoral
Active CNI-based control (Prograf or Neoral)

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Resistencia	Chaco
Argentina	Novartis Investigative Site	San Martin	Buenos Aires
Argentina	Novartis Investigative Site	Santa Fe
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	Camperdown	New South Wales
Australia	Novartis Investigative Site	Clayton	Victoria
Australia	Novartis Investigative Site	Melbourne	Victoria
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Leuven
Estonia	Novartis Investigative Site	Tartu
France	Novartis Investigative Site	Brest
France	Novartis Investigative Site	Nice Cedex 1
France	Novartis Investigative Site	Toulouse Cedex 4
France	Novartis Investigative Site	Tours Cedex
France	Novartis Investigative Site	Vandoeuvre Les Nancy
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt am Main
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover Muenden
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Muenster
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Patras
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	Vishakhapatnam	Andhra Pradesh
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Siena	SI
Italy	Novartis Investigative Site	Torino	TO
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Vilnius
Mexico	Novartis Investigative Site	Aguascalientes
Mexico	Novartis Investigative Site	México	Distrito Federal
Mexico	Novartis Investigative Site	Torreón	Coahuila
Mexico	Novartis Investigative Site	Veracruz
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Leiden
Norway	Novartis Investigative Site	Oslo
Portugal	Novartis Investigative Site	Carnaxide - Linda-A-Velha	Lisboa
Portugal	Novartis Investigative Site	Lisbon
Portugal	Novartis Investigative Site	Porto
Romania	Novartis Investigative Site	Cluj-Napoca	Jud Cluj
Russian Federation	Novartis Investigative Site	Krasnodar
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Nizhnii Novgorod
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	S.-Petersburg
Russian Federation	Novartis Investigative Site	Samara
Russian Federation	Novartis Investigative Site	Volzhskiy
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Hospitalet de Llobregat	Cataluña
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Santander	Cantabria
Spain	Novartis Investigative Site	Zaragoza
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Khon Kaen
Turkey	Novartis Investigative Site	Antalya
Turkey	Novartis Investigative Site	Büyükçekmece / Ýstanbul
Turkey	Novartis Investigative Site	Fatih / Istanbul
Turkey	Novartis Investigative Site	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Estonia,  France,  Germany,  Greece,  India,  Italy,  Latvia,  Lithuania,  Mexico,  Netherlands,  Norway,  Portugal,  Romania,  Russian Federation,  Spain,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison between treatment arms for change from randomization to Month 12 in estimated Glomerular Filtration Rate (eGFR) (MDRD4)	Assessment of renal function by comparing change from randomization to Month 12 in eGFR (MDRD4) between treatment arms for (Full analysis set - 24 month analysis)	Change from randomization to Month 12 in eGFR (MDRD4) -	No
Secondary	Composite efficacy failure as treated biopsy proven acute rejection (BPAR ), graft loss or death		at 12 months post-transplantation	No
Secondary	Comparison of Kaplan-Meier incidence rates of composite efficacy endpoint for each arm at Month 12 and at Month 24 (Full analysis set - 24 month analysis)	Improvement of Left Ventricular Hypertropht (LVH) as assessed by LV mass index (LVMi) using echocardiogram	at 12 months post-transplantation	No
Secondary	Comparison between treatment arms for incidence rates of efficacy endpoints (Full analysis set - 24 month analysis)	Incidence, time to event and severity of treated BPAR = IB; incidence of BPAR that need antibody treatment; incidence of humoral rejection; incidence of treated BPAR = IB	at 12 and 24 months post-transplantation	No
Secondary	Incidence, time to event and severity of any acute rejection (suspected AR, treated acute AR, Biopsy AR, treated biopsy proven AR, subclinical AR)		at 12 and 24 months post-transplantation	No
Secondary	Incidence of adverse events (AEs) and serious adverse events (SAEs)		at 12 and 24 months post-transplantation	No