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

Primary Antiphospholipid Syndrome Clinical Trial

— PAPIRUS  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03540810
• Other study ID #: 2017-004416-19
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: August 15, 2018
• Est. completion date: October 15, 2022

Study information

• Verified date: May 2018
• Source: University Hospital, Angers
• Contact: Cristina C Belizna, Coordinator
• Phone: 0033241356592
• Email: cristina.belizna[@]wanadoo.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: October 15, 2022
• Est. primary completion date: August 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Antiphospholipid Syndrome
• Primary Antiphospholipid Syndrome
• Syndrome

Intervention

Drug:
• 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
• Placebo
The patients will receive placebo with their usual treatment

Locations

Country	Name	City	State
France	University Hospital Angers	Angers

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Angers

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of thrombotic events in each arm after 24 months of treatment	The number of thrombotic events will be compared in the two arms of the study. The events which will be considered are deep venous thrombosis, superficial venous thrombosis, lung embolism, stroke, myocardial infarction as assessed by at least one diagnostic tests such as: doppler echography, lung scintigraphy, lung CT scan, cerebral CT scan, cerebral MRI, myocardial scintigraphy, coronarography.	24 month
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE	The number of participants with treatment-related adverse events as assessed by CTCAE will be compared in the two arms of the study	24 month
Secondary	Number of hospitalizations days related to thrombotic event	The number of hospitalizations days, related to thrombotic event in each arm after 24 months of treatment	24 month
Secondary	Number of work incapacity days related to thrombotic event	The number of work incapacity days, related to thrombotic event in each arm after 24 months of treatment	24 month
Secondary	The specific biological markers of thrombosis in APS such as type and number of antiphospholipid antibodies, complement, antinuclear antibodies, thrombocytosis	The specific biological markers of thrombosis in APS such as type and number of antiphospholipid antibodies, complement, antinuclear antibodies, thrombocytosis in each arm	24 month
Secondary	Assess compliance to VKA	The different recorded values of blood INR all along the study	24 month
Secondary	Assess Assess compliance to HCQ	The values of blood Hydroxychloroquine measured at the end of the 24 months of treatment	24 month
Secondary	The vascular arterial rigidity measured by doppler echography	The vascular arterial rigidity measured by doppler echography will be compared between the two arms of the study at inclusion in the study and after 24 months of treatment	24 month