Clinical trial NCT04153201: Hydroxychloroquine for Thrombosis Prevention and Antiphospholipid Antibody Reduction in Primary Antiphospholipid Syndrome
Official title: Effect of Hydroxychloroquine on Thrombosis Prevention and Antiphospholipid Antibody Levels in Patients With Primary Antiphospholipid Syndrome: An Pilot Randomized Prospective Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Antiphospholipid Syndrome
Keywords: antiphospholipid antibody titers
thrombosis prevention
hydroxychloroquine
antimalarials
antiphospholipid syndrome
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
First posted: 2019-11-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1 intervention arm (Hydroxychloroquine plus standard care), 1 control arm (standard care) Patients randomized 1:1 using block size 2 randomization
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incident acute thrombosis in the venous or arterial circulation
timeFrame: 3 years
Secondary outcomes:
measure: Hydroxychloroquine-related safety outcomes
timeFrame: 3 years
measure: Anticoagulation treatment-related safety outcomes
timeFrame: 3 years
measure: General safety outcomes
timeFrame: 3 years
Other outcomes:
measure: Antiphospholipid antibody titer variation
timeFrame: 3 years
Locations:
city: Athens
country: Greece
facility: Laikon General Hospital
state: Attiki
Study officials:
affiliation: National and Kapodistrian University of Athens
name: Maria G Tektonidou, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: