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

National and Kapodistrian University of Athens50 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Antiphospholipid Syndrome

Interventions

HydroxychloroquineDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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: 1. ≥4 American College of Rheumatology (ACR) classification criteria for Systemic Lupus Erythematosus (SLE) 2. ACR classification criteria for other systemic autoimmune disorders 3. active malignancy 4. treatment with Hydroxychloroquine (HCQ) in the previous 12 months 5. 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

Locations (1)

Laikon General Hospital

Athens, Attica, Greece

Outcomes

Primary Outcomes

Incident acute thrombosis in the venous or arterial circulation

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)

Time frame: 3 years

Secondary Outcomes

Hydroxychloroquine-related safety outcomes

* 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

Time frame: 3 years

Anticoagulation treatment-related safety outcomes

* 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

Time frame: 3 years

Data from ClinicalTrials.gov

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