Study to Evaluate the Efficacy, Safety and Tolerability of Everolimus in de Novo Renal Transplant Recipients Participating in the Eurotransplant Senior Program

Renal Transplantation Clinical Trial

— Senator  

Official title:

6-month, Open-label, Randomized, Multicenter, Prospective, Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Everolimus in de Novo Renal Transplant Recipients Participating in the Eurotransplant Senior Program

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00956293
• Other study ID #: CRAD001ADE19
• Secondary ID: EudraCT-NO. 2008
• Status: Terminated
• Phase: Phase 4
• First received: August 7, 2009
• Last updated: May 23, 2014
• Start date: July 2009
• Est. completion date: March 2013

Study information

• Verified date: May 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

This study wants to address whether a calcineurin-inhibitor (CNI)-free regimen six weeks after transplantation for Eurotransplant Senior Program (ESP) patients is as safe and well tolerated as standard treatment but optimizing immunosuppressive therapy with benefits in renal function, new-onset diabetes mellitus, cardiovascular risk, cancer and allograft nephropathy.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 207
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

Inclusion criteria:

• Patients receiving a primary kidney from a donor aged > 65 years

• In the Eurotransplant Senior Program

• Recipients of de novo cadaveric kidney transplants

Exclusion criteria:

• Multi-organ recipients (e.g., kidney and pancreas)

• Patients receiving a kidney from a non-heart beating donor

• Patients who are recipients of A-B-O incompatible transplants

• Patients with already existing antibodies against the HLA-type of the receiving transplant

• Patients who have received an investigational immunosuppressive drug within four weeks prior to study entry (Baseline visit 1)

• Patients with thrombocytopenia, with an absolute neutrophil count of < 1,500/mm³ or leucopenia or hemoglobin < 6 g/dL

• Patients who are HIV, HCV RNA, or Hepatitis B surface antigen positive

• Evidence of severe liver disease

• Females at randomization who will be not considered post-menopausal

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

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

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

Drug:
• Basiliximab
On day 0, 2 hours prior to transplant and day 4 post-transplant, 20 mg x2 were given to all participants. Post randomization, 20mg at weeks 7 and 12 were given to the Everolimus group.
• Enteric Coated Mycophenolic Acid (MPA)
A loading dose regimen of 2880 mg/day during weeks 1 and 2 (pre-randomization) were given. During weeks 3 - 6 (pre-randomization), 2160 mg/day were given and during weeks 7 - 24, 1440 mg/day were given if tolerated. Dose reductions due to side effects were possible.
• RAD001
Upon randomization, 3 mg (od) on Day 1, and 3 mg (1.5 mg every 12 hours) on Day 2 was given. Afterwards, the dosage was based on blood trough level (5 - 10 ng/mL).
• Cyclosporin A (CsA)
Dosage was based according to blood level
• Corticosteroids
Dosage was administered according to local standards and administration was optional as per clinical need and the Investigators' discretion. Steroid withdrawal occurred after week 2 (pre-randomization).

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Kaiserslautern
Germany	Novartis Investigative Site	Koeln-Merheim
Germany	Novartis Investigative Site	München

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal Function by Glomerular Filtration Rate (GFR) Via Cockcroft-Gault Method	The study was terminated prematurely and not powered for efficacy.	Month 6	No
Secondary	Renal Function by GFR Via Modification of Diet in Renal Diseases (MDRD) and Nankivell Method	The study was terminated prematurely and not powered for efficacy.	Month 6	No
Secondary	Renal Function by Serum Creatinine	The study was terminated prematurely and not powered for efficacy.	Months 6, 12, 24, 36, 48 and 60	No
Secondary	Biopsy Proven Acute Rejection (BPAR), Graft Loss and Death	The study was terminated prematurely and not powered for efficacy.	Months 6, 12, 24, 36, 48 and 60	No
Secondary	Occurrence of Treatment Failures	The study was terminated prematurely and not powered for efficacy.	Month 6	No
Secondary	Evolution of Renal Function (Creatinine Slope)	The study was terminated prematurely and not powered for efficacy.	Week 7, Month 6	No
Secondary	CD25 Saturation on Lymphocytes		Month 6	No
Secondary	Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death	Participants with adverse events (serious plus non-serious), serious adverse events and death were reported.	Months 6, 12, 24, 36, 48 and 60	Yes
Secondary	Renal Function by GFR Over Time		Months 12, 24, 36, 48 and 60	No
Secondary	Renal Function by Proteinuria		Months12, 24, 36, 48 and 60	No