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

NCT03540810 | Unknown Phase 3 DMC

• 1 other identifier: 2017-004416-19
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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

Keywords

antiphospholipid syndrome; thrombosis; hydroxychloroquine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Number of participants with treatment-related adverse events as assessed by CTCAE

  24 month

• Number of hospitalizations days related to thrombotic event

  24 month

• Number of work incapacity days related to thrombotic event

  24 month

• The specific biological markers of thrombosis in APS such as type and number of antiphospholipid antibodies, complement, antinuclear antibodies, thrombocytosis

  24 month

• Assess compliance to VKA

  24 month

Study Arms (2)

Hydroxychloroquine

ACTIVE COMPARATOR

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

Drug: Hydroxychloroquine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Hydroxychloroquine 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

Also known as: HCQ

Hydroxychloroquine

Placebo DRUG

The patients will receive placebo with their usual treatment

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (1)

University Hospital Angers

Angers, 49000, France

Location

MeSH Terms

Conditions

Antiphospholipid Syndrome; Thrombosis

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Cristina Belizna, MD, PhD

  University Hospital, Angers

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cristina C Belizna, Coordinator

CONTACT

0033241356592; cristina.belizna@wanadoo.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2018
• First Posted: May 30, 2018
• Study Start: August 15, 2018
• Primary Completion: August 15, 2022
• Study Completion: October 15, 2022
• Last Updated: May 30, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)