Efficacy and Safety of Enteric-coated Mycophenolate Sodium and Cyclosporine in Combination With and Without Steroids, in Adult Renal Transplant Recipients - Full Text View

Purpose

This study will investigate the efficacy and safety of a steroid avoidance regimen in comparison with steroid treatment in combination with an initially higher dose of enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine microemulsion in de novo renal transplant recipients. Patients will be randomly allocated to receive either EC-MPS or steroids in combination with EC-MPS. Patients of both treatment groups will receive monoclonal antibody induction therapy and a perioperative bolus of steroids and cyclosporine.

Condition	Intervention	Phase
Renal Transplantation	Drug: Enteric-coated mycophenolate sodium (EC-MPS) Drug: Prednisone	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Multicenter Randomized Open Label Study to Assess Efficacy and Safety of a Steroid Avoidance Regimen in Comparison to a Treatment With Steroids, in Combination With Enteric-coated Mycophenolate Sodium (EC-MPS) 2.16 g/d for 6 Weeks and Cyclosporine Microemulsion, in de Novo Adult Renal Transplant Recipients

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation Steroids

Drug Information available for: Prednisone Mycophenolic acid Mycophenolate sodium Cyclosporine Mycophenolate mofetil hydrochloride Mycophenolate mofetil

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Number of Participants With the Occurrence of Treatment Failures at 6 Months Post-transplantation [ Time Frame: 6 months post transplantation ] [ Designated as safety issue: No ]
Treatment failures defined as Biopsy Proven Acute Rejection (BPAR), graft loss, death or loss to follow-up. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection. Graft loss: allograft will be presumed to be lost on the day the patient starts dialysis and is not able to subsequently be removed from dialysis.

Secondary Outcome Measures:

The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
If a participant experienced several BPAR, only the rejection with highest grade is taken into account. Only events that occurred before study treatment discontinuation are taken into account. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection.
Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
A treatment failure is a Biopsy Proven Acute Rejection (BPAR), a graft loss, a death, or a loss to follow-up. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection. Graft loss: The allograft will be presumed lost on the day the patient starts dialysis and is not able to subsequently be removed from dialysis.
Number of Participants With Subclinical Histological Rejections [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
The number of participants with subclinical histological rejections was determined by renal biopsy screening at 3 months in 125 patients, providing adequate samples for 112 biopsies.
Number of Participants With Treatment Failure at 3 Months by Graft Recovery Status [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
The number of participants with treatment failure defined as a Biopsy Proven Acute Rejection (BPAR), a graft loss, a death, or a loss to follow-up at 3 months by graft recovery status.

Delayed graft function is defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day.

Slow graft function is defined as a serum creatinine value > 250 µmol/L at day 5.
Number of Participants Requiring Steroids in Non-steroid Treatment Group [ Time Frame: Months 3 and 6 ] [ Designated as safety issue: Yes ]

Enrollment:	222
Study Start Date:	April 2007
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Without Steroids Patients received Enteric-coated Mycophenolate Sodium (EC-MPS), administered orally 2 times a day for 6 months. Patients also received cyclosporine and a dose of methylprednisolone immediately after transplantation, but did not subsequently receive oral corticosteroids for the remainder of the study.	Drug: Enteric-coated mycophenolate sodium (EC-MPS) An initial dose of 1080 mg EC-MPS was administered immediately before transplantation. Then, during the first 6 weeks post-transplantation, EC-MPS was administered at a dose of 1080 mg twice a day 12 hours apart. From week 7 until the end of the study (month 6), EC-MPS was administered at standard dose of 720 mg twice a day. Other Name: Myfortic
Active Comparator: With Steroids Patients received Enteric-coated Mycophenolate Sodium (EC-MPS), administered orally 2 times a day for 6 months. Patients also received cyclosporine and a dose of methylprednisolone immediately after transplantation, and subsequently continued to receive daily oral prednisone.	Drug: Enteric-coated mycophenolate sodium (EC-MPS) An initial dose of 1080 mg EC-MPS was administered immediately before transplantation. Then, during the first 6 weeks post-transplantation, EC-MPS was administered at a dose of 1080 mg twice a day 12 hours apart. From week 7 until the end of the study (month 6), EC-MPS was administered at standard dose of 720 mg twice a day. Other Name: Myfortic Drug: Prednisone Oral tablets

Arms

Assigned Interventions

Experimental: Without Steroids

Patients received Enteric-coated Mycophenolate Sodium (EC-MPS), administered orally 2 times a day for 6 months. Patients also received cyclosporine and a dose of methylprednisolone immediately after transplantation, but did not subsequently receive oral corticosteroids for the remainder of the study.

Drug: Enteric-coated mycophenolate sodium (EC-MPS)

An initial dose of 1080 mg EC-MPS was administered immediately before transplantation. Then, during the first 6 weeks post-transplantation, EC-MPS was administered at a dose of 1080 mg twice a day 12 hours apart. From week 7 until the end of the study (month 6), EC-MPS was administered at standard dose of 720 mg twice a day.

Other Name: Myfortic

Active Comparator: With Steroids

Patients received Enteric-coated Mycophenolate Sodium (EC-MPS), administered orally 2 times a day for 6 months. Patients also received cyclosporine and a dose of methylprednisolone immediately after transplantation, and subsequently continued to receive daily oral prednisone.

Drug: Enteric-coated mycophenolate sodium (EC-MPS)

An initial dose of 1080 mg EC-MPS was administered immediately before transplantation. Then, during the first 6 weeks post-transplantation, EC-MPS was administered at a dose of 1080 mg twice a day 12 hours apart. From week 7 until the end of the study (month 6), EC-MPS was administered at standard dose of 720 mg twice a day.

Other Name: Myfortic

Drug: Prednisone

Oral tablets

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Primary donor kidney transplant
Panel reactive antibody (PRA) ≤ 20%

Exclusion Criteria:

Multi-organ transplantation including dual kidneys or previous transplant with any other organ different from kidney
Non-heart beating donor or kidney from a non-compatible donor

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00413920

Locations

France
C.H.U. La Milétrie
Poitiers, France

Sponsors and Collaborators

Novartis

Investigators

Study Director:

Novartis

More Information

No publications provided

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00413920 History of Changes
Other Study ID Numbers:	CERL080AFR05
Study First Received:	December 19, 2006
Results First Received:	January 12, 2011
Last Updated:	April 19, 2011
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Novartis:

Steroids avoidance,
enteric-coated mycophenolate sodium (EC-MPS),
de novo renal transplantation

Additional relevant MeSH terms:

Cyclosporins
Cyclosporine
Mycophenolic Acid
Mycophenolate mofetil
Prednisone
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents

Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on May 19, 2013