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.

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

Following publication of results in a medical journal, we are considering sharing data on longitudinal apl titers, demographic information, time to first thrombotic event, adverse events with hydroxychloroquine.

General data protection rule (GDPR) of the European Union special requirements may apply.

Data will become available 6 months following publication of results, and will remain accessible for 2 years

Individual patient data will be provided to researchers in order to perform relevant meta-analyses, after review and approval of the meta-analysis protocol. Potential publications of our results with the same data should be cited if sharing our data results in new publications.