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

NCT00956293 | Terminated Phase 4 Results

• 3 other identifiers: CRAD001ADE19EudraCT-NO. 2008-005109-202008-005109-20
• Study Type: interventional
• Target: 207
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Renal Transplantation

Outcome Measures

Primary Outcomes (1)

• Renal Function by Glomerular Filtration Rate (GFR) Via Cockcroft-Gault Method

  The study was terminated prematurely and not powered for efficacy.

  Month 6

Secondary Outcomes (9)

• Renal Function by GFR Via Modification of Diet in Renal Diseases (MDRD) and Nankivell Method

  Month 6

• Renal Function by Serum Creatinine

  Months 6, 12, 24, 36, 48 and 60

• Biopsy Proven Acute Rejection (BPAR), Graft Loss and Death

  Months 6, 12, 24, 36, 48 and 60

• Occurrence of Treatment Failures

  Month 6

• Evolution of Renal Function (Creatinine Slope)

  Week 7, Month 6

Study Arms (2)

Control group

ACTIVE COMPARATOR

During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group continued with a CNI-based regimen of MPA and CsA.

Drug: Basiliximab; Drug: Enteric Coated Mycophenolic Acid (MPA); Drug: Cyclosporin A (CsA); Drug: Corticosteroids

Everolimus group

EXPERIMENTAL

During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group made a stepwise switch to a CNI-free regimen of everolimus and MPA.

Drug: Basiliximab; Drug: Enteric Coated Mycophenolic Acid (MPA); Drug: RAD001; Drug: Cyclosporin A (CsA); Drug: Corticosteroids

Interventions

Basiliximab DRUG

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.

Also known as: Simulect

Control group; Everolimus group

Enteric Coated Mycophenolic Acid (MPA) DRUG

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.

Also known as: Myfortic

Control group; Everolimus group

RAD001 DRUG

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).

Also known as: RAD001, Certcian

Everolimus group

Cyclosporin A (CsA) DRUG

Dosage was based according to blood level

Also known as: Sandimmun Optoral

Control group; Everolimus group

Corticosteroids DRUG

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).

Control group; Everolimus group

Eligibility Criteria

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

You may qualify if:

• Patients receiving a primary kidney from a donor aged \> 65 years
• In the Eurotransplant Senior Program
• Recipients of de novo cadaveric kidney transplants

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Novartis Investigative Site

Aachen, 52074, Germany

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Düsseldorf, 40225, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Kaiserslautern, 67655, Germany

Location

Novartis Investigative Site

Koeln-Merheim, 51109, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Related Publications (1)

• Brakemeier S, Arns W, Lehner F, Witzke O, Vonend O, Sommerer C, Muhlfeld A, Rath T, Schuhmann R, Zukunft B, Kroeger I, Porstner M, Budde K. Everolimus in de novo kidney transplant recipients participating in the Eurotransplant senior program: Results of a prospective randomized multicenter study (SENATOR). PLoS One. 2019 Sep 19;14(9):e0222730. doi: 10.1371/journal.pone.0222730. eCollection 2019.

  PMID: 31536556 DERIVED

MeSH Terms

Interventions

Basiliximab; Mycophenolic Acid; Everolimus; Cyclosporine; Adrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Sirolimus; Macrolides; Lactones; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

+1 (862) 778-1873

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  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: August 7, 2009
• First Posted: August 11, 2009
• Study Start: July 1, 2009
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: June 6, 2014
• Results First Posted: May 12, 2014

Record last verified: 2014-05

Locations

DE (9)