Evaluation of Early Conversion to Everolimus From Cyclosporine in de Novo Renal Transplant Recipients

NCT00634920 | Completed Phase 4 Results DMC

• 2 other identifiers: CRAD001ASE012007-000771-42
• Study Type: interventional
• Target: 204
• Locations: 3 countries
• Sites: 8

Brief Summary

This study is designed to evaluate if early conversion to everolimus from cyclosporine in de novo renal transplant recipients can improve long-term renal function and slow down the progression of chronic allograft nephropathy

Conditions

Renal Function

Keywords

De novo renal transplantation

Outcome Measures

Primary Outcomes (1)

• Measured Glomerular Filtration Rate

  To compare the efficacy between treatment regimens by assessing the difference in renal function evaluated by mean measured glomerular filtration rate (mGFR) 12 months after renal transplantation (TX). The mGFR was measured using Iohexol or Cr-EDTA clearance according to local practice.

  Month 12

Secondary Outcomes (18)

• Measured Glomerular Filtration Rate

  Month 36

• Calculated Glomerular Filtration Rate

  Months 12, 36

• Progression of Measured Glomerular Filtration Rate

  Week 7, Week 52, Month 36

• Percentage of Participants Who Developed CAN (Chronic Allograft Nephropathy)

  Month 12, Month 36

• Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)

  Months 12, 24, 36

Study Arms (2)

Everolimus (CNI-free)

EXPERIMENTAL

Patients in this group were converted to everolimus immunosuppressive therapy. The patients in the everolimus group were treated with everolimus, off-label (CNI-free) use, and EC-MPS and corticosteroids in accordance with local practice and approved label. Conversion to everolimus was as follows: Day 1: begin everolimus 3 mg in the evening. Usual morning dose of CsA and 50% reduced evening dose of CsA Day 2: everolimus 2 mg in the morning and 2 mg in the evening, complete discontinuation of CsA Day 3 or 4, and onwards: everolimus according to trough level 6-10 ng/mL.The given total daily dose of the immunosuppressive drugs (everolimus) was divided into two (equal) doses, applied 12 hours apart.

Drug: everolimus; Drug: Enteric Coated Mycophenolate Sodium (EC-MPS); Drug: corticosteroids; Drug: Basiliximab

Control (CsA)

ACTIVE COMPARATOR

Patients in the control group continued on an immunosuppressive regimen. The patients in this Control group were treated with CsA, EC-MPS and corticosteroids in accordance with local practice and approved label. The given total daily dose of the immunosuppressive drugs (CsA and EC-MPS) was divided into two (equal) doses, applied 12 hours apart.

Drug: cyclosporine A; Drug: Enteric Coated Mycophenolate Sodium (EC-MPS); Drug: corticosteroids; Drug: Basiliximab

Interventions

everolimus DRUG

Everolimus (Certican®) tablets administered orally in two divided doses (b.i.d.) at a starting dose of 4 mg/day adjusted to target a trough blood concentration between 6 and 10 ng/mL in period 2.

Also known as: Certican

Everolimus (CNI-free)

cyclosporine A DRUG

CsA (Sandimmun Neoral), based on C0-h levels 75-200 ng/mL or C2-h levels 700 900 ng/mL from randomization to Month 6, or C0-h levels 50-150 ng/mL or C2-h levels 600 800 ng/mL from Month 6 to Month 36, according to local method

Also known as: Sndimmun Neoral

Control (CsA)

Enteric Coated Mycophenolate Sodium (EC-MPS) DRUG

Target dose 1440 mg in the control group, target dose 1080 in the everolimus group (higher dose in the CsA group because of interactions of CsA on gastric reabsorption of mycophenolate)

Also known as: Myfortic

Control (CsA); Everolimus (CNI-free)

corticosteroids DRUG

For both groups: minimum corticosteroid dose of 10 mg until week 12, 5-10 mg until month 12, month 12-36 corticosteroid treatment on investigator's descretion.

Also known as: Prednisolone

Control (CsA); Everolimus (CNI-free)

Basiliximab DRUG

Induction therapy 20 mg basiliximab on Day 0 prior to reperfusion and 20 mg on Day 4 post-TX.

Also known as: Simulect

Control (CsA); Everolimus (CNI-free)

Eligibility Criteria

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

You may qualify if:

• First or second single renal transplant from deceased or living donor

You may not qualify if:

• Recipient of organs other than a renal transplant
• Present malignancy (within the last 2 years) other than excised basal cell or squamous cell carcinoma of the skin
• Severe liver disease
• At the time of randomization 7 weeks after transplantation
• In addition to the above criteria the following must be met at time of randomization:
• Patients maintained on a triple immunosuppressive regime consisting of cyclosporine, Enteric coated mycophenolate, and corticosteroids
• Patients completed the first 7 weeks without experiencing any rejection
• Graft loss
• Low hemoglobin value, low number of white blood cells or platelets
• High cholesterol values
• Proteinuria
• Wound healing problems
• Current severe major local or systemic infection
• Renal insufficiency

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Novartis Investigative Site

Aarhus N, 8200, Denmark

Location

Novartis Investigative Site

Copenhagen, DK-2100, Denmark

Location

Novartis Investigative Site

Herlev, 2730, Denmark

Location

Novartis Investigative Site

Odense C, DK-5000, Denmark

Location

Novartis Investigative Site

Oslo, 0424, Norway

Location

Novartis Investigative Site

Gothenburg, 413 45, Sweden

Location

Novartis Investigative Site

Malmo, 205 02, Sweden

Location

Novartis Investigative Site

Uppsala, 751 85, Sweden

Location

MeSH Terms

Interventions

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

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: March 6, 2008
• First Posted: March 13, 2008
• Study Start: March 1, 2008
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: August 13, 2014
• Results First Posted: August 13, 2014

Record last verified: 2014-08

Locations

SE (3); DK (4); NO (1)