Effect of 3g Versus 2 g MMF in Combination With Tacrolimus on Progression of Renal Allograft Interstitial Fibrosis

Comparison of 3g Versus 2g Mycophenolate Mofetil in Combination With Tacrolimus on Progression of Chronic Histology Changes in Kidney Transplant Recipients

Development of chronic changes (scarring) in transplanted kidney tissue is a major cause of long-term kidney function deterioration and ultimately graft loss. It results from both immunologic and non-immunologic mechanisms. Mycophenolate mofetil (MMF) is immunosuppressive drug used for prevention of rejection after kidney transplant, usually in combination with a calcineurin inhibitor (tacrolimus or cyclosporine), with or without corticosteroids. Besides immunosuppression, MMF may also have direct antifibrotic properties. Tacrolimus has potent immunosuppressive effects and is the cornerstone of contemporary posttransplant immunosuppressive therapy in kidney recipients. However, it is also nephrotoxic. The hypothesis of the present study is that in the setting of similar net immunosuppression, higher dose of MMF (3 g daily) will result in slower progression of kidney fibrosis during first year posttransplant as compared to MMF 2 g daily. To test this hypothesis, the present study will randomly assign low immunological risk kidney transplant recipients to either 2g or 3 g MMF daily, in combination with tacrolimus, with, or without maintenance steroids. All patients will have kidney biopsy at implantation and at 12 months after transplantation. Main outcome will be 1-year change in chronic kidney histology (interstitial fibrosis) assessed by protocol biopsy.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation; Kidney Failure
• Intervention / Treatment: Drug: Mycophenolate mofetil

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Contacts and Locations

Study Locations

• Croatia
  • HR
    • Zagreb, HR, Croatia, 10000
      • Clinical Hospital Merkur

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. first kidney or kidney-pancreas transplantation
2. CDC PRA <=20%

Exclusion Criteria:

1. dual kidney transplantation
2. AB0 incompatible transplantation
3. 0 biopsy ci, ct, cv, or ah score >=2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MMF 3g daily	Drug: Mycophenolate mofetil; Mycophenolate will be administered to all study patients at dose of 3 g daily for the first seven days posttransplant. Afterwards, study patients will continue, as randomized, on either 3 g, or 2 g MMF daily.
Active Comparator: MMF 2 g daily	Drug: Mycophenolate mofetil; Mycophenolate will be administered to all study patients at dose of 3 g daily for the first seven days posttransplant. Afterwards, study patients will continue, as randomized, on either 3 g, or 2 g MMF daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression of interstitial fibrosis (ci)	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Graft loss	1 year
Patient survival	1 year
Estimated glomerular filtration rate	1 year
Time to first acute rejection episode	up to 1 year
Progression of other chronic scores	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of infections requiring hospitalization		1 year
Frequency of CMV viremia		1 year
Frequency of BK viremia		1 year
Frequency of BK nephropathy		1 year
Development of donor-specific antibodies		1 year
Renal morphology and hemodynamics assessed by ultrasound	Subset of study patients	1 year

Collaborators and Investigators

• Sponsor: Clinical Hospital Merkur
• Collaborators: University Hospital Rijeka; University Medical Centre Ljubljana

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: May 18, 2013
• First Submitted That Met QC Criteria: May 21, 2013
• First Posted (Estimate): May 22, 2013

Study Record Updates

• Last Update Posted (Actual): October 26, 2021
• Last Update Submitted That Met QC Criteria: October 18, 2021
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: kidney transplantation; Chronic; mycophenolate mofetil; chronic allograft dysfunction
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: CHMerkur