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NCT Number: NCT04153201

Hydroxychloroquine for Thrombosis Prevention and Antiphospholipid Antibody Reduction in Primary Antiphospholipid Syndrome

This is an interventional drug study designed as a pilot for a randomized clinical trial, aimed at assessing the effect of hydroxychloroquine on the incidence rate of thrombosis in patients with primary antiphospholipid syndrome as the main outcome, as well as the safety of hydroxychloroquine administration in this population. In addition, the effect of hydroxychloroquine on antiphospholipid antibody titers will be assessed.

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Key information

Conditions

Antiphospholipid Syndrome Autoimmune Diseases Immune System Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Laikon General Hospital

Athens, Attica, 11527, Greece

About this study

Patients with primary antiphospholipid syndrome (either thrombotic or obstetric) on regular follow-up at our outpatient rheumatology department and being treated with standard care (systemic anticoagulants and/or antiplatelet agents), are randomized to receive either hydroxychloroquine plus standard care, or standard care alone, on a 1:1 ratio using block size 2 randomization, after exclusion of patients with contraindications to hydroxychloroquine or prior hydroxychloroquine use within 12 months of consideration for enrollment. Patients are monitored clinically every 3 months and the development of thrombosis and/or adverse effects attributable to hydroxychloroquine is recorded. Antiphospholipid antibody titers (anti-cardiolipin immunoglobulin G (IgG)/Immunoglobulin M (IgM) and anti-beta2-glycoprotein I IgG/IgM isotypes) are measured semi-annually. Intention-to-treat survival analysis is applied for assessing the effect of hydroxychloroquine on the incidence of thrombosis. Longitudinal mixed linear models are applied for assessing the effect of hydroxychloroquine on longitudinal titers of antiphospholipid antibodies.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Adult patients diagnosed with primary antiphospholipid syndrome (PAPS) [updated Sapporo criteria: Miyakis et al, J Thromb Haemost. 2006 Feb;4(2):295-306. PubMed 16420554]

Exclusion criteria

  • ≥4 American College of Rheumatology (ACR) classification criteria for Systemic Lupus Erythematosus (SLE)
  • ACR classification criteria for other systemic autoimmune disorders
  • active malignancy
  • treatment with Hydroxychloroquine (HCQ) in the previous 12 months
  • history of serious adverse events or contraindication to HCQ including a history of HCQ allergy, HCQ eye toxicity, or glucose-6-phosphate dehydrogenase deficiency, uncontrolled seizure disorder, liver enzyme elevation >2-fold the upper normal limit, and creatinine clearance <30ml/min

Treatment and study plan

Hydroxychloroquine

Drug

Hydroxychloroquine 200 mg daily for patients weighing < 60 kg, hydroxychloroquine 400 mg daily for patients weighing >= 60 kg

Other names: Antimalarials, Plaquenil

Primary outcomes

  1. Incident acute thrombosis in the venous or arterial circulation

    Time frame: 3 years

    incident acute arterial thrombosis (myocardial infarction, stroke, transient ischemic attack, occlusion of the peripheral limb and neck, splanchnic, or retinal arteries) or venous thrombosis (pulmonary embolism, deep vein thrombosis, splanchnic vein thrombosis, retinal vein occlusion) confirmed by appropriate imaging studies (doppler ultrasonography, computed tomography pulmonary angiogram, conventional angiography, magnetic resonance angiography, ventilation/perfusion lung scintigraphy)

Secondary outcomes

  1. Hydroxychloroquine-related safety outcomes

    Time frame: 3 years

    • Retinal toxicity by ocular examination, visual field testing and optical coherence tomography yearly and upon reporting visual symptoms
    • Toxic myopathy: new onset motor strength <=4/5, myalgia and creatine kinase elevation
    • Liver toxicity: liver enzyme elevations >3x of upper limit of normal (ULN), or serum total bilirubin >2x ULN, with no cholestasis
    • Metabolism disorders (hypoglycemia, weight decrease) by quarterly body weight and blood glucose testing
    • Bone marrow suppression: drop in hemoglobin to < 10 mg/dl, white blood cells < 3700/μL, platelets < 150,000/μL according to a hematologist
    • Cardiac complications (conduction defects, QT prolongation, cardiomyopathy) screened by interview, physical examination, and semi-annual electrocardiogram
    • Seizures screened by interview and confirmed by electrocardiogram
    • Gastrointestinal upset, allergic reactions, skin reactions by interview and physical exam

  2. Anticoagulation treatment-related safety outcomes

    Time frame: 3 years

    • Major bleeding, defined as fatal bleeding, or symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a fall in hemoglobin level of 2 g/dL or more, or leading to transfusion of two or more units of whole blood or red cells.
    • Minor bleeding defined as clinically evident bleeding not fulfilling the definition of major bleeding

  3. General safety outcomes

    Time frame: 3 years

    • Hospitalization for any cause
    • Death of any cause
    • APS-related death (based on death certificate records)

Other outcomes

  1. Antiphospholipid antibody titer variation

    Time frame: 3 years

    Anticardiolipin IgG antibody titers, anti-cardiolipin IgM antibody titers, anti-beta2-glycoprotein I IgG antibody titers, antibeta2-glycoprotein I IgM antibody titers measured every 6 months.

Sponsors and collaborators

Lead sponsor

National and Kapodistrian University of Athens

Other

Registry information

Official study title

Effect of Hydroxychloroquine on Thrombosis Prevention and Antiphospholipid Antibody Levels in Patients With Primary Antiphospholipid Syndrome: An Pilot Randomized Prospective Study.

Important dates

Study start
2013
Primary completion
2019
Study completion
2019
First posted
Nov 6, 2019
Registry last updated
Nov 6, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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