Mycophenolate Mofetil for IgA Nephropathy

Sponsor

The University of Hong Kong (Other)

Overall Status

Completed

CT.gov ID

NCT00863252

Collaborator

United Christian Hospital (Other), Queen Mary Hospital, Hong Kong (Other)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

IgA nephropathy (IgAN) is the commonest primary glomerulonephritis worldwide. In Hong Kong, IgAN accounts for approximately 30% of all primary glomerular diseases, and a significant proportion of young patients (< 50 years of age) on dialysis therapy are sufferers of primary IgAN. To date, no specific therapeutic agent has been consistently shown to halt the progression of IgAN to end-stage renal failure, particularly in patients with persistent significant proteinuria and the presence of chronic tubulointerstitial inflammation on kidney biopsy. In recent years, angiotensin-converting enzyme inhibitors (ACEI) have been found capable of significantly reducing proteinuria in some IgAN patients, while others, particularly those with the ACE DD genotype, showed either absent or unsatisfactory response to angiotensin blockade. Mycophenolate mofetil (MMF) is a marketed immunosuppressive drug which acts by releasing mycophenolic acid (MPA) to inhibit the de novo pathway of purine synthesis, and hence is relatively selective for lymphocytes. Apart from being efficacious for the prophylaxis of renal allograft rejection and for the induction of remission in severe lupus nephritis, MMF has been anecdotally reported to avert progression to allograft failure in recurrent IgAN of the transplanted kidney. Data on the clinical efficacy of MMF in the treatment of primary IgAN, however, is lacking. In the current proposal, we aim to study the clinical efficacy of MMF in patients with biopsy-proven IgAN and clinically significant proteinuria despite angiotensin blockade. Patients will be followed up for at least 5 years to track any survival difference between groups.

Condition or Disease	Intervention/Treatment	Phase
IGA Nephropathy	Drug: mycophenolate mofetil Drug: angiotensin blockade	Phase 4

Detailed Description

(i) STUDY DESIGN

This will be a prospective, randomized, open-label, case-controlled study. Patients of either gender with biopsy-proven IgAN and clinically significant proteinuria despite being on ACEI treatment will be potential candidates (see selection criteria). Eligible patients will be randomized into either of the following groups:

Group I (Intervention arm):

Patients will be given MMF at a daily dose of 1.5 g orally in 2 divided doses in addition to concurrent medications, including ACEI. Duration of therapy is expected to be six months.

Group II (Control arm):

Patient will continue to receive all concurrent medications, including ACEI or angiotensin receptor blocker, at the discretion of the attending renal physician.

(ii) PATIENT SELECTION CRITERIA Inclusion criteria

Males or females between the ages of 18 and 70 years
Renal biopsy showing a histological diagnosis IgAN, with predominant or codominant mesangial deposition of IgA on immunofluorescent studies
Daily urinary protein excretion > 1 g on at least 3 separate occasions
Serum creatinine < 400 umol/L
Patients who are willing to give written informed consent and to participate in and comply with the study protocol

Exclusion criteria

Presence of concomitant glomerular diseases
Patients with known hypersensitivity to MMF
Patients receiving treatment with other cytotoxic agents
Serum creatinine > 400 umol/L
Women who are lactating, pregnant or of childbearing potential not using, or who are unwilling to use, a reliable contraceptive method during and for 6 weeks following conclusion of MMF therapy. A pregnancy test to exclude pregnancy will be performed for women of childbearing potential prior to recruitment
Patients who are unable or unwilling to give written informed consent and to participate in and comply with the study protocol
Presence of systemic infection or malignancy requiring therapy at the time of entry to the study
Patients simultaneously participating in another study or who have participated in another study within the last 30 days of entry into this study

(iii) PATIENT MONITORING

Patient record

The record of every recruited patient will contain the following information:

Demographic data
Medical history including concomitant illness
All concomitant medications
Other significant information

Timing of Assessments

All study assessments will be calculated from the date of study entry. The study follow-up schedule will be as follows:

Baseline, then
Two-weekly for the first month, then
Monthly for the 2nd - 6th month, at the end of which MMF will be withdrawn, then
Three-monthly until at least 5 years of follow up

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Prospective, Randomized, Open Label, Case-Controlled Study on the Efficacy of Mycophenolate Mofetil for IgA Nephropathy Patients With Heavy Proteinuria Despite Angiotensin Blockade

Study Start Date :

Mar 1, 2002

Actual Primary Completion Date :

Jun 1, 2004

Actual Study Completion Date :

Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 MMF	Drug: mycophenolate mofetil Orally at 0.75 g bd to 1 g bd for 6 months
Active Comparator: 2 Control	Drug: angiotensin blockade Continuation of angiotensin blockade

Arm

Intervention/Treatment

Experimental: 1

MMF

Drug: mycophenolate mofetil

Orally at 0.75 g bd to 1 g bd for 6 months

Active Comparator: 2

Control

Drug: angiotensin blockade

Continuation of angiotensin blockade

Outcome Measures

Primary Outcome Measures

24 hour urinary protein excretion [18 months to 5 years]

Secondary Outcome Measures

Renal survival Serum creatinine level and creatinine clearance Urine albumin-to-creatinine ratio [at least 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males or females between the ages of 18 and 70 years
Renal biopsy showing a histological diagnosis IgAN, with predominant or codominant mesangial deposition of IgA on immunofluorescent studies
Daily urinary protein excretion > 1 g on at least 3 separate occasions
Serum creatinine < 400 umol/L
Patients who are willing to give written informed consent and to participate in and comply with the study protocol

Exclusion Criteria:

Presence of concomitant glomerular diseases
Patients with known hypersensitivity to MMF
Patients receiving treatment with other cytotoxic agents
Serum creatinine > 400 umol/L
Women who are lactating, pregnant or of childbearing potential not using, or who are unwilling to use, a reliable contraceptive method during and for 6 weeks following conclusion of MMF therapy. A pregnancy test to exclude pregnancy will be performed for women of childbearing potential prior to recruitment
Patients who are unable or unwilling to give written informed consent and to participate in and comply with the study protocol
Presence of systemic infection or malignancy requiring therapy at the time of entry to the study
Patients simultaneously participating in another study or who have participated in another study within the last 30 days of entry into this study