Hydroxychloroquine Versus Placebo: Impact on Thrombotic Relapse in Primary Antiphospholipid Syndrome (PAPIRUS)

University Hospital, Angers

Status and phase: Unknown; Phase 3

Conditions: Primary Antiphospholipid Syndrome

Treatments: Drug: Placebo; Drug: Hydroxychloroquine

Study type: Interventional

Funder types: Other

Identifiers

NCT03540810

2017-004416-19

Details and patient eligibility

About

Antiphospholipid syndrome (APS) combines thrombotic (venous and/or arterial) and/or obstetrical manifestations, along with biological anomalies related to the presence of antiphospholipid antibodies. Despite actual treatment recommended by international guidelines, the relapse rate in APS is high and survival is 65% at 15 years. Hydroxychloroquine has demonstrated its efficacy and benefits in the treatment of Systemic Lupus Erythematosus, but there is no current consensus concerning the efficacy of this treatment in the secondary prevention of thrombotic events in primary APS, even though several in vitro experimental and animal model data, along with several clinical studies have suggested a beneficial effect of this drug in this indication. Considering the prevalence of primary APS in the general population and of the number of clinical events observed in patients with primary APS and receiving conventional treatment with vitamin K anticoagulants (VKA), the consortium expects a minimum clinically relevant difference of 70%. Considering a prevalence of thrombotic events for the entire studied primary APS population of 10% at 2 years, the consortium expects a 70% decrease in thrombotic events under Hydroxychloroquine treatment administered in addition to VKA treatment in primary APS, i.e. a 3% prevalence in the Hydroxychloroquine group at 2 years. The consortium proposes a drug trial, phase III, national multicentric, comparative, randomized, superiority, double-blind, controlled with 2 compared groups (Hydroxychloroquine versus placebo) study. The enrolment period will be 24 months.

The main aim of this trial is to comparatively assess at 24 months the number of new thrombotic events (venous and arterial) in primary antiphospholipid syndrome in patients treated with VKA plus Hydroxychloroquine versus VKA plus placebo, in a multicentre, prospective randomized, double-blind, versus placebo study.

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age >18 years
• Presence of a primary antiphospholipid syndrome with previous venous/arterial thrombosis and which needs a treatment with VKA
• Patients with a signed commitment

Exclusion criteria

• Secondary APS

• Ocular diseases :

  • retinal disease contraindicating the prescription of hydroxychloroquine
  • cataract
  • monophtalmic

• Past history of intolerance or allergy to hydroxychloroquine

• Known deficit in G6PDase

• Hemolytic anemia

• Porphyria

• Chronic hepatic disease

• Severe renal failure (creatinin clearence <30ml/min)

• Chronic alcoholism

• Patient with QT interval >440 ms on the ECG

• Concomitant treatment with drugs raising the QT interval

• Epilepsy

• Pregnant or breastfeeding women

• Women refusing an effective contraception

• Active cancer or malignant hemopathy

• Psychiatric disease unabling the compliance to treatment

• Unaffiliated person or not beneficiary of a social security system

• Concomitant participation at a biomedical trial able to interfere with the actual trial

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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300 participants in 2 patient groups, including a placebo group

Hydroxychloroquine

Active Comparator group

Description:

All patients randomised in this arm will receive hydroxychloroquine with their usual treatment, which is antivitamin K anticoagulants

Treatment:

Drug: Hydroxychloroquine

Placebo

Placebo Comparator group

Description:

All patients randomised in this arm will receive a placebo with their usual treatment, which is antivitamin K anticoagulants

Treatment:

Drug: Placebo