"Steroids and Azathioprine Versus Steroids Alone in IgAN"

Sponsor

A. Manzoni Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00755859

Collaborator

(none)

206

Enrollment

Locations

Arms

112

Duration (Months)

7.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In a previous trial the investigators found that the effect of steroids in IgA nephropathy diminish over time. The difference in renal survival is striking up till the third year, but then remains constant. A six-month course of steroid therapy may be not enough to ensure a stable remission. The investigators hypothesized that a more aggressive treatment may obtain long-term better results. The investigators conducted a randomised controlled trial to assess the utility of low-dose azathioprine added to steroids in adult IgAN patients.

Condition or Disease	Intervention/Treatment	Phase
IGA Nephropathy	Drug: steroids plus azathioprine Drug: steroids	Phase 4

Detailed Description

In 1999, we published a multicenter, randomized, controlled trial, which compared a 6-month steroid course with supportive therapy in 86 patients with IgAN. After 5 years of follow-up, the risk of a 50% increase in plasma creatinine from baseline was significantly lower in the treated patients; proteinuria also decreased. However, the effect of steroids seemed to diminish over time. The difference in renal survival was particularly striking up till the third year, but then remained constant. We hypothesised that a six-month course of steroid therapy is not enough to ensure a stable remission, and a more aggressive treatment may be required to obtain long-term better results. At this regard, some studies of combined treatment with corticosteroids and azathioprine found that treatment was effective in preserving renal function and in reducing proteinuria. However, these studies did not clarify whether azathioprine added further benefit to steroids in the long term. We conducted a randomised controlled trial to assess the utility of low-dose azathioprine added to steroids in adult IgAN patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

206 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Corticosteroids and Azathioprine Versus Corticosteroids Alone in IgA Nephropathy: a Randomized Controlled Trial.

Study Start Date :

May 1, 1998

Actual Primary Completion Date :

Dec 1, 2004

Actual Study Completion Date :

Sep 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Six month steroid course plus azathioprine	Drug: steroids plus azathioprine methylprednisolone 1 g i.v. for three consecutive days at the beginning of months 1, 3 and 5, followed by oral prednisone 0.5 mg/kg every other day plus azathioprine 1.5 mg/kg/day for six months Other Names: solumedrol deltacortene azatioprina
Active Comparator: 2 six month steroid course	Drug: steroids methylprednisolone 1 g i.v. for three consecutive days at the beginning of months 1, 3 and 5, followed by oral prednisone 0.5 mg/kg every other day for six months Other Names: solumedrol deltacortene

Arm

Intervention/Treatment

Experimental: 1

Six month steroid course plus azathioprine

Drug: steroids plus azathioprine

methylprednisolone 1 g i.v. for three consecutive days at the beginning of months 1, 3 and 5, followed by oral prednisone 0.5 mg/kg every other day plus azathioprine 1.5 mg/kg/day for six months

Other Names:

solumedrol

deltacortene

azatioprina

Active Comparator: 2

six month steroid course

Drug: steroids

methylprednisolone 1 g i.v. for three consecutive days at the beginning of months 1, 3 and 5, followed by oral prednisone 0.5 mg/kg every other day for six months

Other Names:

solumedrol

deltacortene

Outcome Measures

Primary Outcome Measures

progression of renal disease, estimated by the time to 50% increase in plasma creatinine from baseline. [Every month for the first six months, then six months]

Secondary Outcome Measures

evolution of proteinuria over time [every months for the first six months and then every six months]
safety [every months for the first six months and then every six months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

biopsy proven IgA nephropathy
creatinine ≤ 2.0 mg/dl for at least three months
proteinuria ≥ 1.0 g/day for at least three months

Exclusion Criteria:

treatment with steroids or cytotoxic drugs during the previous three years
contraindications to steroids or azathioprine
Henoch-Schöenlein purpura
diabetes mellitus
severe hypertension (diastolic blood pressure > 120 mmHg)
lupus erythematosus systemicus
malignancies
active peptic-ulcer disease
pregnancy
viral hepatitis or other infections

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital "Bolognini"	Seriate	BG	Italy
2	Hospital of Montichiari	Montichiari	Brescia	Italy
3	Hospital "S.Anna"	Como	CO	Italy	22100
4	Hospital "Istituti Ospitalieri"	Cremona	CR	Italy
5	Hospital "S.Marta e S.Venera",	Acireale	CT	Italy
6	Hospital "S.Vincenzo"	Taormina	CT	Italy
7	Department of Nephrology and Dialysis, A. Manzoni Hospital	Lecco	LC	Italy	23900
8	Hospital "Maggiore"	Lodi	LO	Italy
9	Hospital "Uboldo"	Cernusco sul Naviglio	MI	Italy
10	Hospital of Desio	Desio	MI	Italy
11	Hospital "Maggiore" IRCCS	Milano	MI	Italy
12	Hospital "A.Segni"	Ozieri	Nuoro	Italy
13	Hospital "Spedali Civili"	Brescia		Italy
14	"G. Brotzu" Hospital	Cagliari		Italy
15	Hospital "Cannizzaro"	Catania		Italy
16	Hospital "Careggi"	Firenze		Italy
17	Hospital of University	Foggia		Italy
18	Hospital "C. Poma"	Mantova		Italy
19	Hospital "S. Francesco"	Nuoro		Italy
20	Hospital "V. Cervello"	Palermo		Italy
21	University Hospital	Parma		Italy
22	Fondazione Maugeri" IRCCS	Pavia		Italy
23	CNR-IBIM	Reggio Calabria		Italy
24	Hospital "S. Maria Nuova"	Reggio Emilia		Italy
25	Hospital of Sondrio	Sondrio		Italy
26	CMID	Torino		Italy
27	Hospital "Belcolle"	Viterbo		Italy
28	Inselspital	Bern		Switzerland