protocolSection identificationModule nctId: NCT06291025, orgStudyIdInfo id: 2021/0374/HP, briefTitle: Efficacy and Safety of Immunosuppression, Caplacizumab and Plasma Infusion Without Therapeutic Plasma Exchange in Immune-mediated Thrombotic Thrombocytopenic Purpura: Multicentric Non-inferiority Single-arm Study, acronym: PEX-FREE, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-04-01, primaryCompletionDateStruct date: 2026-08-01, completionDateStruct date: 2026-08-01, studyFirstPostDateStruct date: 2024-03-04, lastUpdatePostDateStruct date: 2024-03-04, sponsorCollaboratorsModule leadSponsor name: University Hospital, Rouen, class: OTHER, descriptionModule briefSummary: Immune thrombotic thrombocytopenic purpura (iTTP) is caused by a severe, autoantibody-mediated deficiency of ADAMTS13 leading to an accumulation of ultra-large von Willebrand factor multimers in plasma and finally to microthrombi in blood vessels. The current standard of care of iTTP consists in the triple association of daily plasma exchange (PEX, 60 ml/kg/day), immunosuppressive agents and anti-adhesive treatment (Caplacizumab). Our group recently reported the outcome of 90 patients with iTTP treated with this triple association and when compared to historical patients, the triplet regimen prevented death, refractoriness and exacerbations. Likewise, plasma volumes were reduced by 2 to 3-fold and we could reduce the median number of PEX sessions from 13 to 6. PEX is an invasive and time-consuming procedure, associated with catheter and plasma-related complications ranging from 22% to 30%. Consequently, to alleviate the burden of care in iTTP, using a regimen without PEX would represent a major and topical goal. Attempts to treat patients with plasma infusion (PI) without PEX were previously reported and provided evidence that large volumes of PI (20-30 ml/kg/day) improved the initial outcome of iTTP. However, fluid overload occurred in most cases after 5-7 days, limiting the feasibility of this strategy. Nevertheless, the recent availability of caplacizumab opens the perspective of treating patients with plasma for a shorter period. Recently, strategies without PEX have been carried out in Jehovah's Witnesses with iTTP \[5\]. Impressively, improvement was rapid and comparable to those provided with a standard PEX-based treatment. Additionally, a treatment combining caplacizumab and immunosuppression only was successfully performed in six iTTP patients with severe neurologic and/or cardiac involvement. The rapid and durable improvement provides evidence that a regimen without plasma seems feasible. However, we consider that robust data are still lacking to completely remove plasmatherapy from iTTP management. Based on these statements, we wish here to address the efficacy and safety of a PEX-free regimen, combining PI only (15 ml/kg/day), corticosteroids/rituximab, and caplacizumab., conditionsModule conditions: Thrombotic Microangiopathies, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: NA, interventionModel: SINGLE_GROUP, interventionModelDescription: This trial is prospective, non-comparative, non-inferiority, single-arm, multicentric, national., primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 131, type: ESTIMATED, armsInterventionsModule interventions name: PEX-FREE, outcomesModule primaryOutcomes measure: To evaluate the efficacy of a PEX-FREE regimen in adults with iTTP as assessed by the proportion of participants day-30 post-plasma therapy death, refractoriness, exacerbation or an ADAMTS13 activity < 20%., eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule, hasResults: False