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

NCT ID: NCT03540810

Last Updated: 2018-05-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-15
• Study Completion Date: 2022-10-15

Brief Summary

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.

Conditions

Primary Antiphospholipid Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Hydroxychloroquine

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

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine

Intervention Type: DRUG

The patients will additionally receive this drug with their usual treatment to evaluate its efficiency to prevent new thrombotic events in primary antiphospholipid syndrome patients

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The patients will receive placebo with their usual treatment

Interventions

Hydroxychloroquine

The patients will additionally receive this drug with their usual treatment to evaluate its efficiency to prevent new thrombotic events in primary antiphospholipid syndrome patients

Intervention Type: DRUG

Placebo

The patients will receive placebo with their usual treatment

Intervention Type: DRUG

Other Intervention Names

HCQ

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Angers

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cristina Belizna, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Angers

Locations

University Hospital Angers

Angers, , France

Countries

France

Central Contacts

Cristina C Belizna, Coordinator

Role: CONTACT

cristina.belizna@wanadoo.fr

0033241356592

Other Identifiers

2017-004416-19

Identifier Type: -

Identifier Source: org_study_id