Clinical trial NCT03540810: Hydroxychloroquine Versus Placebo: Impact on Thrombotic Relapse in Primary Antiphospholipid Syndrome
Official title: Hydroxychloroquine Versus Placebo: Impact on Thrombotic Relapse in Primary Antiphospholipid Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Primary Antiphospholipid Syndrome
Keywords: antiphospholipid syndrome
thrombosis
hydroxychloroquine
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2018-05-30
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of thrombotic events in each arm after 24 months of treatment
timeFrame: 24 month
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE
timeFrame: 24 month
measure: Number of hospitalizations days related to thrombotic event
timeFrame: 24 month
measure: Number of work incapacity days related to thrombotic event
timeFrame: 24 month
measure: The specific biological markers of thrombosis in APS such as type and number of antiphospholipid antibodies, complement, antinuclear antibodies, thrombocytosis
timeFrame: 24 month
measure: Assess compliance to VKA
timeFrame: 24 month
measure: Assess Assess compliance to HCQ
timeFrame: 24 month
measure: The vascular arterial rigidity measured by doppler echography
timeFrame: 24 month
Other outcomes:
Locations:
city: Angers
country: France
facility: University Hospital Angers
Study officials:
affiliation: University Hospital, Angers
name: Cristina Belizna, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: