Mycophenolate Mofetil (MMF) in Patients With IgA Nephropathy (IgAN) - Full Text View

Sponsored by:	Sun Yat-sen University
Information provided by:	Sun Yat-sen University
ClinicalTrials.gov Identifier:	NCT00657059

Purpose

A multi-center, randomized, controlled clinical trial to evaluate the short-term and long-term efficacy and safety of mycophenolate mofetil (MMF) in reducing proteinuria and preserving renal function in patients with IgAN who have pre-treated (and continue to be treated) with angiotensin II receptor blockers (ARB), compared to the corticosteroids.

Condition	Intervention	Phase
IGA Nephropathy	Drug: irbesartan Drug: methylprednisolone (MP) or prednisone (pred) Drug: mycophenolate mofetil (MMF)	Phase III

Drug Information available for: Methylprednisolone Prednisone Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Phenylephrine Guaifenesin Naphazoline Naphazoline hydrochloride Oxymetazoline Oxymetazoline hydrochloride Phenylephrine hydrochloride Phenylpropanolamine Phenylpropanolamine hydrochloride Irbesartan 16-Methyleneprednisolone

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Prospective, Multicenter, Randomized Controlled Trial of Mycophenolate Mofetil (MMF) in Patients With IgA Nephropathy (IgAN)

Further study details as provided by Sun Yat-sen University:

Primary Outcome Measures:

Remission of proteinuria (complete or partial) [ Time Frame: 2007-2013 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine (SCr) levels, or a 25% decline from baseline eGFR levels, or onset of end-stage renal disease or dialysis treatment, or kidney transplantation) [ Time Frame: 2007-2013 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	150
Study Start Date:	September 2007
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Pred Group: Prednisone treatment	Drug: irbesartan In the ARB lead-in phase, each subject will be on a strict sodium-restricted diet ( < 5 g NaCl/day), and then given a stable dose (150mg ~ 300mg/day) of irbesartan (Aprovel) for 3 months until reaching the target blood pressure (BP) level of ≤ 125/75 mmHg. Patients will continue ARB treatment in the drug treatment phase and at lease 3 years in the follow-up phase. Drug: methylprednisolone (MP) or prednisone (pred) Patients will take oral Pred ( 0.5 mg/kg/d) on alternate days, and on the first, third and fifth months of the drug treatment phase, patients will be given intravenous pulse therapy with methylprednisolone ( 0.5 g/day) for 3 successive days. And after 6 months, Pred should be tapered to be stopped until the end of the 12-month course of treatment.
2: Active Comparator MMF Group: MMF treatment	Drug: irbesartan In the ARB lead-in phase, each subject will be on a strict sodium-restricted diet ( < 5 g NaCl/day), and then given a stable dose (150mg ~ 300mg/day) of irbesartan (Aprovel) for 3 months until reaching the target blood pressure (BP) level of ≤ 125/75 mmHg. Patients will continue ARB treatment in the drug treatment phase and at lease 3 years in the follow-up phase. Drug: mycophenolate mofetil (MMF) Patients will take MMF 1.0g bid (wt ≥ 50kg) or 0.75g bid (wt ＜ 50kg) for the first 6-month of drug treatment phase, then to 0.5 bid (wt ≥ 50kg) for the remaining 6-month.
3: Active Comparator Pred plus MMF Group: Prednisone plus MMF treatment	Drug: irbesartan In the ARB lead-in phase, each subject will be on a strict sodium-restricted diet ( < 5 g NaCl/day), and then given a stable dose (150mg ~ 300mg/day) of irbesartan (Aprovel) for 3 months until reaching the target blood pressure (BP) level of ≤ 125/75 mmHg. Patients will continue ARB treatment in the drug treatment phase and at lease 3 years in the follow-up phase. Drug: methylprednisolone (MP) or prednisone (pred) Patients will take oral Pred ( 0.5 mg/kg/d) on alternate days, and on the first, third and fifth months of the drug treatment phase, patients will be given intravenous pulse therapy with methylprednisolone ( 0.5 g/day) for 3 successive days. And after 6 months, Pred should be tapered to be stopped until the end of the 12-month course of treatment. Drug: mycophenolate mofetil (MMF) Patients will take MMF 1.0g bid (wt ≥ 50kg) or 0.75g bid (wt ＜ 50kg) for the first 6-month of drug treatment phase, then to 0.5 bid (wt ≥ 50kg) for the remaining 6-month.

Detailed Description:

There are four phases of study for each subject. Phase 1 the screening phase. During this phase each potential subject will be evaluated to determine if he/she is eligible for the study.

Phase 2 the ARB lead-in phase will last for three months. Phase 3 the intervention phase. Each subject will be randomly received 12 months treatment with the study drugs (MMF, prednisone or MMF plus prednisone) Phase 4 following-up phase. All the patients will be followed by 3 years after study drug stopped.

Eligibility

Ages Eligible for Study:	14 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Willingness to sign an informed consent
Age:14~60 years, regardless of gender
Clinical evaluation and renal biopsy diagnostic for IgAN, excluded secondary IgAN. Renal histological criteria should be defined by Lee's glomerular grading system.
1 g/day <= proteinuria < 3.5 g/day, or UPr/Cr ratio ≥ 0.6 (male) or ≥ 0.8 (female) when taking ARB
eGFR ≥ 40 mL/min/1.73 m2

Exclusion Criteria:

Inability or unwillingness to sign the informed consent
Inability or unwillingness to meet the scheme demands raised by the investigators
Rapidly progressive nephritic syndrome and acute renal failure, including rapidly progressive IgAN ( IgAN with rapid decline in renal function characterized histologically by necrotizing vasculitis and crescent formation≥30%) necessitating the use of other immunosuppressive agents.
Secondary IgAN such as systemic lupus erythematosus, Henoch-Schonlein purpuric nephritis and hepatitis B -associated nephritis
est GFR < 40 mL/min/1.73m2
Malignant hypertension that is difficult to be controlled by oral drugs
Cirrhosis, chronic active liver disease.
History of significant gastrointestinal disorders (e.g. severe chronic diarrhea or active peptic ulcer disease.)
Any Active systemic infection or history of serious infection within one month of entry or known infection with HIV, hepatitis B, or hepatitis C.
Other major organ system disease (e.g. serious cardiovascular diseases including congestive heart failure , chronic obstructive pulmonary disease, asthma requiring oral steroid treatment or central nervous system diseases)
Malignant tumors (except fully cured basal cell carcinoma)
Absolute neutrophil count ＜ 1500／mm3, absolute platelet count ＜75000／mm3 or hematocrit (Hct) <28% (anemic subjects may be reevaluated after the anemia has been treated.)
Known allergy, contraindication or intolerance to the MMF, corticosteroids or ACEI/ARB.
Pregnancy or breast feeding at the time of entry or unwillingness to comply with measures for contraception
Current exposure to MMF or azathioprine. In case of current treatment with oral steroid or ACEI/ARB, entry is permitted after corticosteroids or ACEI/ARB are stopped for 2 weeks.
Current or recent (within 30 days) exposure to any other investigational drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00657059

Contacts

Contact: Xueqing Yu, MD	8620-87766335	yuxq@mail.sysu.edu.cn>
Contact: Qiongqiong Yang, MD	8620-87755766 ext 8843	qqyzzm@yahoo.com.cn

Locations

China, Guangdong
The 1st Affiliated Hospital, Sun Yet-sen University	Recruiting
guangzhou, Guangdong, China, 510080
Contact: Xueqing Yu, MD 8620-87766335 yuxq@mail.sysu.edu.cn>
Contact: Qiongqiong Yang 8620-87755766 ext 8843 qqyzzm@yahoo.com.cn
Principal Investigator: Xueqing Yu, MD

Sponsors and Collaborators

Sun Yat-sen University

Investigators

Principal Investigator:	Xueqing Yu, MD	Department of Nephrology, 1st Affiliated Hospital, Sun Yat-Sen University
Principal Investigator:	Yunha Liao, MD	Department of Nephrology, 1st Affiliated Hospital of Guangxi Medical University
Principal Investigator:	Jinli Zhang, MD	Department of nephrology, People's Hospital of Yunnan Province
Principal Investigator:	Junzhou Fu, MD	Department of Nephrology,1st People's Hospital of Guangzhou
Principal Investigator:	Anping Xu, MD	Department of Nephrology, 2nd Affiliated Hospital of Sun Yet-Sen University
Principal Investigator:	Weiqiang Zhong, MD	Department of Nephrology, Centrical People's Hospital of Huizhou City
Principal Investigator:	Zaiseng Zhou, MD	Department of Nephrology, People's Hospital of Zhongshan City
Principal Investigator:	zhangsuo liu, MD	Department of Nephrology, 1st Affiliated hospital of Zhengzhou University, Henan
Principal Investigator:	Tanqi lou, MD	3nd affiliated hospital of Sun yatsent university, Guangzhou

More Information

Responsible Party:	Sun Yat-sen University ( Xueqing Yu/Director )
Study ID Numbers:	SYSU-PRGIgAN-001
Study First Received:	April 8, 2008
Last Updated:	October 9, 2008
ClinicalTrials.gov Identifier:	NCT00657059
Health Authority:	China: State Food and Drug Administration

Keywords provided by Sun Yat-sen University:

IgA nephropathy
mycophenolate mofetil

Study placed in the following topic categories:

Prednisone
Glomerulonephritis
Autoimmune Diseases
Methylprednisolone
Mycophenolic Acid
Irbesartan
Methylprednisolone acetate
Prednisolone acetate
Angiotensin II
Naphazoline
Oxymetazoline

Urologic Diseases
Guaifenesin
Phenylephrine
Nephritis
Prednisolone
Mycophenolate mofetil
Berger disease
Glomerulonephritis, IGA
Kidney Diseases
Phenylpropanolamine
Methylprednisolone Hemisuccinate

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Antibiotics, Antineoplastic
Neuroprotective Agents
Hormones
Therapeutic Uses
Immune System Diseases
Antineoplastic Agents, Hormonal

Gastrointestinal Agents
Enzyme Inhibitors
Cardiovascular Agents
Antihypertensive Agents
Glucocorticoids
Protective Agents
Immunosuppressive Agents
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009