Clinical trial NCT00755859: "Steroids and Azathioprine Versus Steroids Alone in IgAN"
Official title: Corticosteroids and Azathioprine Versus Corticosteroids Alone in IgA Nephropathy: a Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: IGA Nephropathy
Keywords: IgA nephropathy
steroids
azathioprine
chronic kidney disease progression
proteinuria
Lead sponsor: A. Manzoni Hospital
Sponsor class: OTHER
First posted: 2008-09-19
Enrollment: 206
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: progression of renal disease, estimated by the time to 50% increase in plasma creatinine from baseline.
timeFrame: Every month for the first six months, then six months
Secondary outcomes:
measure: evolution of proteinuria over time
timeFrame: every months for the first six months and then every six months
measure: safety
timeFrame: every months for the first six months and then every six months
Other outcomes:
Locations:
city: Seriate
country: Italy
facility: Hospital "Bolognini"
state: BG
city: Montichiari
country: Italy
facility: Hospital of Montichiari
state: Brescia
city: Como
country: Italy
facility: Hospital "S.Anna"
state: CO
city: Cremona
country: Italy
facility: Hospital "Istituti Ospitalieri"
state: CR
city: Acireale
country: Italy
facility: Hospital "S.Marta e S.Venera",
state: CT
city: Taormina
country: Italy
facility: Hospital "S.Vincenzo"
state: CT
city: Lecco
country: Italy
facility: Department of Nephrology and Dialysis, A. Manzoni Hospital
state: LC
city: Lodi
country: Italy
facility: Hospital "Maggiore"
state: LO
city: Cernusco sul Naviglio
country: Italy
facility: Hospital "Uboldo"
state: MI
city: Desio
country: Italy
facility: Hospital of Desio
state: MI
city: Milano
country: Italy
facility: Hospital "Maggiore" IRCCS
state: MI
city: Ozieri
country: Italy
facility: Hospital "A.Segni"
state: Nuoro
city: Brescia
country: Italy
facility: Hospital "Spedali Civili"
city: Cagliari
country: Italy
facility: "G. Brotzu" Hospital
city: Catania
country: Italy
facility: Hospital "Cannizzaro"
city: Firenze
country: Italy
facility: Hospital "Careggi"
city: Foggia
country: Italy
facility: Hospital of University
city: Mantova
country: Italy
facility: Hospital "C. Poma"
city: Nuoro
country: Italy
facility: Hospital "S. Francesco"
city: Palermo
country: Italy
facility: Hospital "V. Cervello"
city: Parma
country: Italy
facility: University Hospital
city: Pavia
country: Italy
facility: Fondazione Maugeri" IRCCS
city: Reggio Calabria
country: Italy
facility: CNR-IBIM
city: Reggio Emilia
country: Italy
facility: Hospital "S. Maria Nuova"
city: Sondrio
country: Italy
facility: Hospital of Sondrio
city: Torino
country: Italy
facility: CMID
city: Viterbo
country: Italy
facility: Hospital "Belcolle"
city: Bern
country: Switzerland
facility: Inselspital
Study officials:
affiliation: A Manzoni Hospital, Lecco, Italy
name: Claudio Pozzi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A Manzoni Hospital, Lecco, Italy
name: Francesco Locatelli, MD
role: STUDY_CHAIR
affiliation: A Manzoni Hospital, Lecco, Italy
name: Simeone Andrulli, MD
role: STUDY_DIRECTOR
affiliation: Hospital "G. Brotzu", Cagliari, Italy
name: Antonello Pani, MD
role: STUDY_DIRECTOR
affiliation: Hospital "G. Brotzu", Cagliari, Italy
name: Paolo Altieri, MD
role: STUDY_DIRECTOR
affiliation: Hospital "Maggiore" IRCCS, Milan, Italy
name: Gian B Fogazzi, MD
role: STUDY_DIRECTOR
affiliation: Hospital "Maggiore" IRCCS, Milan, Italy
name: Claudio Ponticelli, MD
role: STUDY_DIRECTOR
References:
citation: Locatelli F, Pozzi C, Del Vecchio L, Andrulli S, Pani A, Fogazzi G, Altieri P, Ponticelli C. Combined treatment with steroids and azathioprine in IgA nephropathy: design of a prospective randomised multicentre trial. J Nephrol. 1999 Sep-Oct;12(5):308-11.