Enteric-coated Mycophenolate Sodium (EC-MPS) With Reduced-dose Tacrolimus Versus EC-MPS With Standard-dose Tacrolimus in Stable Kidney Transplant Recipients

NCT00284934 | Completed Phase 3 Results

• 1 other identifier: CERL080AFR04
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

This study introduces a new optimization immunosuppressive regimen associating tacrolimus at a reduced dose and enteric-coated mycophenolate sodium at an increased dose in order to slow down renal function worsening and to prevent the progression of chronic allograft nephropathy, while maintaining the same efficacy, in maintenance renal transplant recipients.

Conditions

Kidney Diseases

Keywords

Dose optimization; immune suppressive regimen; enteric-coated mycophenolate sodium; EC-MPS; renal transplantation; kidney; transplant; maintenance patients; Renal transplantation in maintenance

Outcome Measures

Primary Outcomes (1)

• Renal Function Assessed by Change in Estimated Glomerular Filtration Rate(eGFR)

  Change in estimated glomerular filtration rate from baseline to Month 6 calculated by using abbreviated Modification of Diet in Renal Disease (MDRD) formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR \[mL/min/1.73m\^2\] = 186.3\*(C\^-1.154)\*(A\^-0.203)\*G\*R where -C is the serum concentration of creatinine \[mg/dL\], -A is patient age at sample collection date \[years\], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1.

  Baseline and Month 6

Secondary Outcomes (3)

• Renal Function at 3 Months Assessed by Change in Estimated Glomerular Filtration Rate (eGFR)

  Baseline and 3 months

• Number of Participants With Treatment Failure Parameters (Biopsy-Proven Acute Rejection (BPAR), Graft Loss, Death, or Loss to Follow-up) at 6 Months

  6 months

• Number of Participants With Graft and Patient Survivals at 6 Months

  6 months

Study Arms (2)

Standard dose EC-MPS

ACTIVE COMPARATOR

Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus dose (twice a day orally) adjusted to maintain the trough blood level (C0) contained between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.

Drug: Enteric-coated mycophenolate sodium (EC-MPS); Drug: Tacrolimus; Drug: Corticosteroids

High EC-MPS

EXPERIMENTAL

Patients received 1440 mg/day (720 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus dose (twice a day orally) tapered to reach a trough blood level target contained between 2 and 4.5 ng/mL within 15 days after randomization at the most. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.

Drug: Enteric-coated mycophenolate sodium (EC-MPS); Drug: Tacrolimus; Drug: Corticosteroids

Interventions

Enteric-coated mycophenolate sodium (EC-MPS) DRUG

Also known as: Myfortic

High EC-MPS; Standard dose EC-MPS

Tacrolimus DRUG

Also known as: Prograf

High EC-MPS; Standard dose EC-MPS

Corticosteroids DRUG

At a dose of at least 5 mg/day.

Also known as: Prednisone

High EC-MPS; Standard dose EC-MPS

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary or secondary kidney transplant
• Treatment with mycophenolic acid (MMF 1 g/d or EC-MPS 720 mg/d) and tacrolimus (trough concentration \[C0\] ≥ 5.5 ng/mL)
• Creatinine clearance ≥ 30 mL/min and \< 60 mL/min and stable renal function

You may not qualify if:

• Multi-organ recipients or previous transplant with any other organ different from kidney
• Biopsy proven acute rejection or treated acute rejection within the last 3 months.
• Prescription of mycophenolate mofetil 1 g/d or mycophenolate sodium 720 mg/d due to adverse event occurrence when higher doses were administered

Sponsors & Collaborators

• Novartis: lead

Study Sites (1)

Novartis

Basel, Switzerland

Location

Related Publications (1)

• Kamar N, Rostaing L, Cassuto E, Villemain F, Moal MC, Ladriere M, Barrou B, Ducloux D, Chaouche K, Quere S, Di Giambattista F, Be F. A multicenter, randomized trial of increased mycophenolic acid dose using enteric-coated mycophenolate sodium with reduced tacrolimus exposure in maintenance kidney transplant recipients. Clin Nephrol. 2012 Feb;77(2):126-36. doi: 10.5414/CN107227.

  PMID: 22257543 DERIVED

MeSH Terms

Conditions

Kidney Diseases

Interventions

Mycophenolic Acid; Tacrolimus; Adrenal Cortex Hormones; Prednisone

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis

  Novartis

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 30, 2006
• First Posted: February 1, 2006
• Study Start: December 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: May 2, 2011
• Results First Posted: May 2, 2011

Record last verified: 2011-03

Locations

CH (1)