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

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ClinicalTrials.gov Identifier: NCT03540810
Recruitment Status : Not yet recruiting
First Posted : May 30, 2018
Last Update Posted : May 30, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Angers

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.


Condition or disease Intervention/treatment Phase
Primary Antiphospholipid Syndrome Drug: Hydroxychloroquine Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Hydroxychloroquine Versus Placebo: Impact on Thrombotic Relapse in Primary Antiphospholipid Syndrome
Estimated Study Start Date : August 15, 2018
Estimated Primary Completion Date : August 15, 2022
Estimated Study Completion Date : October 15, 2022


Arm Intervention/treatment
Active Comparator: Hydroxychloroquine
All patients randomised in this arm will receive hydroxychloroquine with their usual treatment, which is antivitamin K anticoagulants
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
Other Name: HCQ

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




Primary Outcome Measures :
  1. Number of thrombotic events in each arm after 24 months of treatment [ Time Frame: 24 month ]
    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.


Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE [ Time Frame: 24 month ]
    The number of participants with treatment-related adverse events as assessed by CTCAE will be compared in the two arms of the study

  2. Number of hospitalizations days related to thrombotic event [ Time Frame: 24 month ]
    The number of hospitalizations days, related to thrombotic event in each arm after 24 months of treatment

  3. Number of work incapacity days related to thrombotic event [ Time Frame: 24 month ]
    The number of work incapacity days, related to thrombotic event in each arm after 24 months of treatment

  4. The specific biological markers of thrombosis in APS such as type and number of antiphospholipid antibodies, complement, antinuclear antibodies, thrombocytosis [ Time Frame: 24 month ]
    The specific biological markers of thrombosis in APS such as type and number of antiphospholipid antibodies, complement, antinuclear antibodies, thrombocytosis in each arm

  5. Assess compliance to VKA [ Time Frame: 24 month ]
    The different recorded values of blood INR all along the study

  6. Assess Assess compliance to HCQ [ Time Frame: 24 month ]
    The values of blood Hydroxychloroquine measured at the end of the 24 months of treatment

  7. The vascular arterial rigidity measured by doppler echography [ Time Frame: 24 month ]
    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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03540810


Contacts
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Contact: Cristina C Belizna, Coordinator 0033241356592 cristina.belizna@wanadoo.fr

Locations
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France
University Hospital Angers Active, not recruiting
Angers, France, 49000
Sponsors and Collaborators
University Hospital, Angers
Investigators
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Principal Investigator: Cristina Belizna, MD, PhD University Hospital, Angers

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Responsible Party: University Hospital, Angers
ClinicalTrials.gov Identifier: NCT03540810     History of Changes
Other Study ID Numbers: 2017-004416-19
First Posted: May 30, 2018    Key Record Dates
Last Update Posted: May 30, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by University Hospital, Angers:
antiphospholipid syndrome
thrombosis
hydroxychloroquine

Additional relevant MeSH terms:
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Syndrome
Antiphospholipid Syndrome
Disease
Pathologic Processes
Autoimmune Diseases
Immune System Diseases
Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents