Mycophenolate Mofetil for IgA Nephropathy

NCT ID: NCT00863252

Last Updated: 2009-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-03-31
• Study Completion Date: 2009-03-31

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.

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

Conditions

IGA Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

MMF

Group Type: EXPERIMENTAL

mycophenolate mofetil

Intervention Type: DRUG

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

2

Control

Group Type: ACTIVE_COMPARATOR

angiotensin blockade

Intervention Type: DRUG

Continuation of angiotensin blockade

Interventions

mycophenolate mofetil

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

Intervention Type: DRUG

angiotensin blockade

Continuation of angiotensin blockade

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United Christian Hospital

OTHER

Sponsor Role: collaborator

Queen Mary Hospital, Hong Kong

OTHER

Sponsor Role: collaborator

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

The University of Hong Kong

Principal Investigators

Sydney CW Tang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

Department of Medicine and Geriatrics, United Christian Hospital

Hong Kong, , China

Countries

China

References

Tang S, Leung JC, Chan LY, Lui YH, Tang CS, Kan CH, Ho YW, Lai KN. Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy. Kidney Int. 2005 Aug;68(2):802-12. doi: 10.1111/j.1523-1755.2005.00460.x.

Reference Type: RESULT

PMID: 16014059 (View on PubMed)

Other Identifiers

Roche-ST-01

Identifier Type: -

Identifier Source: org_study_id