Therapeutic Effect of Hydroxychloroquine on Immunoglobulin A (IgA) Nephropathy Course QUIgAN Study
- Conditions
- IgA Nephropathy
- Interventions
- Drug: Placebo oral tablet
- Registration Number
- NCT06350630
- Brief Summary
immunoglobulin A (IgA) nephropathy (Berger disease) is the most frequent primary glomerulonephritis worldwide. This disease accounts for about 5% of the causes of end stage renal disease in France, representing a major public health issue. Its pathophysiology seems to be triggered by mucosal immunity abnormalities leading to the systemic misaddressing of mucosal IgA, generation of circulating immunoglobulin A1 (IgA1) immune complexes finally deposited in renal glomeruli leading to renal tissue inflammation and scarring processes. Among this pathogeny, innate immunity is involved at several steps, including mucosal immunity.
In this regard, hydroxychloroquine has been shown to generate a global anti-inflammatory effect, particularly through its action on Toll like receptors and dendritic cells. This drug is well tolerated, widely used for other auto-immune diseases (e.g. Systemic Lupus Erythematosus) and very low priced.
One randomized controlled study conducted in China has recently shown a significant drop in proteinuria of IgA nephropathy patients treated with hydroxychloroquine (-48.4%) compared to the placebo group (+10.0%), after a quite short-term follow-up (6 months) and a moderate statistical power (30 patients in each group).
Considering (i) the potential mechanism of therapeutic effect on this disease, (ii) the well documented safety profile of the drug for rheumatologic indications and posologies, and its low cost (iii) its efficacy in reducing proteinuria in IgA nephropathy patients in a preliminary Chinese randomized control study, the investigators aim in this study at establishing the beneficial impact of hydroxychloroquine on IgA nephropathy in a double blind randomized controlled trial on a Caucasian French population with harder outcomes and a longer follow-up compared to the Chinese preliminary study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 334
- Social security affiliation
- Signed informed consent
- With biopsy proven IgA nephropathy (any vintage)
- With urine albumin/creatinine > 300mg/g,
- under maximal tolerated labeled dose of renin-angiotensin-aldosterone system (RAAS) inhibitors for at least 3 months
- With at least one Oxford lesion (M, E, S, T, C) on last available kidney biopsy
- With estimate GFR above 15 mL/min/1,73m² (Chronic Kidney Disease - EPIdemiology collaboration CKD-EPI formula)
- With at least one contraceptive method for women of childbearing age
- Secondary IgA nephropathy (Henoch Schonlein purpura, cirrhosis, inflammatory bowel disease)
- Corticosteroid or immunosuppressive therapies in the past year before screening
- Contra-indication to hydroxychloroquine (retinopathy, maculopathy, history of intolerance to hydroxychloroquine...)
- Uncontrolled hypertension (systolic blood pression> 160 mmHg and/or diastolic blood pression >110 mmHg )
- Long QT interval and/or QT prolonging medicines
- Pregnancy or lactation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo oral tablet - Hydroxychloroquine Hydroxychloroquine Oral Tablet Active hydroxychloroquine once daily by oral route at 6.5 mg/kg of ideal weight/day, with maximal dose of 400/mg day
- Primary Outcome Measures
Name Time Method Absolute difference in estimate Glomerular Filtration Rate (GFR) between hydroxychloroquine group and control group evolution 3 years
- Secondary Outcome Measures
Name Time Method nephrological follow-up: systolic and diastolic blood pressure 3 years death 3 years nephrological follow-up: albuminuria 3 years nephrological follow-up: hematuria 3 years end stage renal disease (GFR< 15mL/min/1.73m²) 3 years nephrological follow-up: proteinuria 3 years nephrological follow-up: GFR 2 years adverse events (pruritus, gastro-intestinal disorders) and serious adverse events (QT enlargement, cardiomyopathy, ophthalmologic disorders, neuromyopathy, cytopenia) 3 years
Trial Locations
- Locations (7)
CHU Gabriel Montpied
🇫🇷Clermont-Ferrand, France
Hospices Civils de Lyon
🇫🇷Lyon, France
AP-HM Hôpital de la Conception
🇫🇷Marseille, France
APHP Hôpital Bichat
🇫🇷Paris, France
APHP Hôpital de Tenon
🇫🇷Paris, France
CHU Lyon Sud
🇫🇷Pierre-Bénite, France
CHU de Saint-Etienne
🇫🇷Saint-Étienne, France