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| Name | Class |
|---|---|
| Ministry of Health, France | OTHER_GOV |
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Systemic vasculitis are inflammatory diseases of the blood vessels, responsible for systemic manifestations. Among the systemic vasculitis affecting small blood vessels, IgA vasculitis (IgAV) is one of the most common forms and mainly affects the skin, joints, kidneys and gastrointestinal tract. Kidney and gastrointestinal damage can be serious, causing complications and life-threatening sequelae, especially in adults. The treatment of adult-onset IgAV is still a matter of debate. Glucocorticoids have been the standard of care for inducing remission for years in severe forms of IgAV. However, not all patients achieve remission and may experience disease flares associated with increased morbidity and mortality. In addition, the cumulative side effects of glucocorticoids are also major causes of long-term adverse events and death.Rituximab (RTX), an anti-CD20 monoclonal antibody, has been shown to be spectacularly effective in inducing remission in d 'other small vascular vessels, in particular ANCA-associated vasculitis and cryoglobulinemic vasculitis, with an acceptable safety profile.
Recently, a multicenter observational study suggested that RTX was an effective and safe therapeutic option for treating relapsed and / or refractory adult IgAV.
Overall, RTX may be an effective and safe therapeutic approach in adult IgAVs, justifying the need for a prospective randomized controlled trial evaluating Rituximab as an induction of remission for adult IgAV.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| experimental group | Experimental | Experimental therapeutic strategy based on the use of rituximab in combination with glucocorticoids |
|
| control group | Placebo Comparator | Control therapeutic strategy based on glucocorticoids plus placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rituximab Injection | Drug | anti-CD20 monoclonal antibody leading to B-cell depletion, in relapsing and/or refractory IgAV patients |
|
| Measure | Description | Time Frame |
|---|---|---|
| Rituximab efficacy | The proportion of patients alive who achieved remission with a prednisone dose of 0 mg/day at 180 days | 180 days |
| Rituximab efficacy | The proportion of patients alive who achieved remission with a prednisone dose of 0 mg/day at 360 days | 360 days |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of rituximab-based regimen to induce remission | Proportion of patients with BVAS=0 (or BVAS of ≤5 if all scores were due to persistent hematuria or proteinuria) and a prednisone dose ≤5 mg/day at 180 days | 180 days |
| Efficacy of rituximab-based regimen to induce remission |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Romain Paule, Dr | Hôpital Foch | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital La Cavale Blanche | Brest | 29200 | France | |||
| CHU Clermont Ferrand |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12401245 | Result | Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR. Incidence of Henoch-Schonlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet. 2002 Oct 19;360(9341):1197-202. doi: 10.1016/S0140-6736(02)11279-7. | |
| 28605168 | Result | Audemard-Verger A, Terrier B, Dechartres A, Chanal J, Amoura Z, Le Gouellec N, Cacoub P, Jourde-Chiche N, Urbanski G, Augusto JF, Moulis G, Raffray L, Deroux A, Hummel A, Lioger B, Catroux M, Faguer S, Goutte J, Martis N, Maurier F, Riviere E, Sanges S, Baldolli A, Costedoat-Chalumeau N, Roriz M, Puechal X, Andre M, Lavigne C, Bienvenu B, Mekinian A, Zagdoun E, Girard C, Berezne A, Guillevin L, Thervet E, Pillebout E; French Vasculitis Study Group. Characteristics and Management of IgA Vasculitis (Henoch-Schonlein) in Adults: Data From 260 Patients Included in a French Multicenter Retrospective Survey. Arthritis Rheumatol. 2017 Sep;69(9):1862-1870. doi: 10.1002/art.40178. |
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Design of trial :
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This trial will be comparative, randomized, double-blind and double-dummy in order to limit performance and evaluation bias.
Neither patients, nor physicians will know the treatments allocated to their patients.
Investigators will be in blind of the leukocyte formula during all study period, from day 1.
Neither patients, nor physicians will know the treatments allocated to their patients.
Investigators will be in blind of the CD19+ count during all study period, from day 15.
| placebo | Drug | placebo experimental treatment |
|
|
Proportion of patients with BVAS=0 (or BVAS of ≤5 if all scores were due to persistent hematuria or proteinuria) and a prednisone dose ≤5 mg/day at 360 days |
| 360 days |
| Assessement the duration of remission | Proportion of patients achieving remission for ≥3 consecutive months over the 360 days, with BVAS=0 (or BVAS of ≤5 if all scores were due to persistent hematuria or proteinuria) and a prednisone dose ≤5 mg/day at 360 days. | 360 days |
| Assessment of patients achieving a complete or partial renal remission & renal outcome remission | Proportion of patients in complete renal and partial renal remission at 180 days (Renal parameters at 180 days compared with baseline: eGFR, daily proteinuria, hematuria, arterial hypertension, use of angiotensin converting enzyme inhibitor, occurrence of end-stage renal disease) | 180 days |
| Assessment of patients achieving a complete or partial renal remission & renal outcome remission | Proportion of patients in complete renal and partial renal remission at 360 days (Renal parameters at 360 days compared with baseline: eGFR, daily proteinuria, hematuria, arterial hypertension, use of angiotensin converting enzyme inhibitor, occurrence of end-stage renal disease) | 360 days |
| Measure of glucocorticoids dose | Area under the curve for prednisone dose at 180 days in the two treatment groups | 160 days |
| Measure of glucocorticoids dose | Area under the curve for prednisone dose at 360 days in the two treatment groups | 360 days |
| Number of participants with adverse events for the safety analyse | Adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at days 180 and 360 for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, malignancies, venous thromboembolic events, hospitalization resulting either from the disease or from a complication due to the study treatment, infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions, death | 360 days |
| The sequelae assessed by the Vasculitis Damage Index | The Vasculitis Damage Index in the two treatment groups | 180 days |
| The sequelae assessed by the Vasculitis Damage Index | The Vasculitis Damage Index in the two treatment groups | 360 days |
| Quality of life of patients | HAQ and SF-36 questionnaires at 180 days | 180 days |
| Quality of life of patients | HAQ and SF-36 questionnaires at 360 days | 360 days |
| Patient reported outcome | The patient-reported outcomes (PRO) including patient-reported disease activity, anxiety and depression, burden of the disease and treatment and adherence to treatment, at days 180 and 360 after randomization in the two treatment groups, and during the long-term follow-up | 360 days |
| Patient survival | Number of patient survival | 360 days |
| Clermont-Ferrand |
| 63000 |
| France |
| CHU Clermont Ferrand | Clermont-Ferrand | 63003 | France |
| Hôpital Edouard Herriot | Lyon | 69003 | France |
| CHU Marseille | Marseille | 13005 | France |
| APHM de La Timone | Marseille | 13385 | France |
| Hôpital André Grégoire | Montreuil | 93100 | France |
| CHU Nantes | Nantes | 44093 | France |
| CHU Nîmes (Caremeau) | Nîmes | 30029 | France |
| Hôpital Cochin | Paris | 75679 | France |
| CHU Strasbourg | Strasbourg | 67091 | France |
| Hôpital Foch | Suresnes | 92150 | France |
| CHU Toulouse | Toulouse | 31059 | France |
| CHRU Bretonneau | Tours | 37044 | France |
| ID | Term |
|---|---|
| D011695 | IgA Vasculitis |
| ID | Term |
|---|---|
| D014657 | Vasculitis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D011693 | Purpura |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020141 | Hemostatic Disorders |
| D006474 | Hemorrhagic Disorders |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007105 | Immune Complex Diseases |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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