Registry on Augmented Antithrombotic Treatment Regimens for Patients With Arterial Thrombotic APS

The goal of this registry is to gather more information on the efficacy and safety of various antithrombotic regimens. The registry collects data on patients with antiphospholipid syndrome and an arterial event within the past 12 months, on treatment with either A) a VKA with therapeutic range, INR 2.0-3.0 plus low-dose aspirin (75-100 mg daily), B) a VKA alone with therapeutic range, INR 2.0-3.0, C) a VKA with therapeutic range, INR 3.0-4.0, or D) with a dual antiplatelet regimen. The follow-up is 2 years.

Study Overview

• Status: Recruiting
• Conditions: Antiphospholipid Syndrome; Arterial Thrombosis
• Intervention / Treatment: Drug: Dual antiplatelet therapy; Drug: Combined antithrombotic therapy; Drug: Vitamin K antagonist standard intensity; Drug: Vitamin K antagonist high intensity

Detailed Description

The optimal antithrombotic management of patients with antiphospholipid syndrome and arterial thrombotic events is unclear. The guidelines provide several options, mostly with vitamin K antagonist with/without an antiplatelet agent. Dual antiplatelet therapy (DAPT) was in a meta-analysis potentially effective, but included studies were few and small.

The primary aim is to compare a vitamin K antagonist (VKA), i.e. warfarin, acenocoumarol, phenprocoumon etc, with international normalized ratio 2.0-3.0 plus low-dose aspirin (75-100 mg) with DAPT - typically low-dose aspirin plus clopidogrel (75 mg daily) but other combinations will be acceptable. The registry will also include patients treated with VKA alone at standard- or high-intensity, since this is recommended and will serve as reference groups in comparison with VKA + low-dose aspirin and versus DAPT. The outcomes are (efficacy) arterial or venous thromboembolism, vascular death or (safety) major bleeding.

A secondary objective is to analyze how the cardiovascular risk factors (hypertension, hyperlipidemia, obesity, smoking, diabetes, and heart failure), venous thrombotic risk factors (previous venous thromboembolism, cancer, immobility, chronic inflammatory disease) and anti-phospholipid profile contribute to recurrent arterial thrombosis.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Sam Schulman, MD, PhD; Phone Number: 44810 +19055270271; Email: schulms@mcmaster.ca
• Study Contact Backup: Name: Hannah Cohen, MD, FRCP; Phone Number: 9456 +442034477368; Email: hannah.cohen@ucl.ac.uk

Study Locations

• Argentina
  • Córdoba, Argentina
    • Recruiting
    • Clínica Universitaria Reina Fabiola
    • Contact: Soledad Molnar, MD; Phone Number: 0351-4142121
  • Buenos Aires F.D.
    • Buenos Aires, Buenos Aires F.D., Argentina, C1113 AAJ
      • Recruiting
      • Instituto de Investigaciones en Salud Pública, Universidad de Buenos Aires
      • Contact: Patricia Casais, MD, PhD; Phone Number: (11)50324141; Email: patricia.casais@odontologia.uba.ar
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L9H 7M1
      • Recruiting
      • McMaster University
      • Contact: Sam Schulman; Phone Number: 9059796437; Email: schulms@mcmaster.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The decision on the treatment regimen should have been made by the treating physician on clinical grounds and judgement, prior to informing the patients about the registry. The information should include that vitamin K antagonist is the recommended standard, either alone or in combination and, in case dual antiplatelet regimen is chosen, an explanation to the patient for what reasons it should be used or continued. Patients that have been started on either of the eligible regimens after the most recent arterial thromboembolic event and within the past 12 months can be approached and informed about the study. If the patient meets the inclusion criteria and does not have any of the exclusion criteria, the investigator or designated representative obtains consent for collection of data.

Description

Inclusion Criteria:

1. Patients of at least 18 years of age with confirmed antiphospholipid syndrome according to Sydney criteria and with first or recurrent arterial thrombotic manifestation, including those with asymptomatic brain infarcts on diagnostic imaging.
2. Treatment with either A) a vitamin K antagonist (VKA) with therapeutic range, international normalized ratio (INR) 2.0-3.0 plus low-dose aspirin (75-100 mg daily), B) a VKA alone with therapeutic range, INR 2.0-3.0 or C) VKA with therapeutic range, INR 3.0-4.0, or D) with a dual antiplatelet regimen, if considered appropriate by the treating physician.
3. Signed informed consent obtained (in jurisdictions where required).

Exclusion Criteria:

1. Inability to follow the patient due to geographical or other reasons.
2. Patients with documented poor compliance.
3. Bleeding risk that in the opinion of the treating physician makes combination antithrombotic therapy unsafe.
4. Pregnancy or planned pregnancy.
5. Venous thrombotic event diagnosed after the last arterial event.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with thromboembolism verified by diagnostic imaging, electrocardiogram or troponin rise	Composite of arterial thrombosis (stroke, myocardial infarction, peripheral arterial thrombosis or embolism), venous thromboembolism (thrombosis in any deep vein or pulmonary embolism), and vascular death.	2 years
Number of Participants with major hemorrhage fulfilling at least one of the International Society on Thrombosis and Haemostasis criteria	Major hemorrhage according to the International Society on Thrombosis and Haemostasis	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with arterial thrombosis verified by diagnostic imaging	stroke, myocardial infarction, peripheral arterial thrombosis or embolism	2 years
Number of Participants with venous thromboembolism verified by diagnostic imaging	thrombosis in any deep vein or pulmonary embolism	2 years
Number of Participants with vascular death verified by diagnostic imaging, electrocardiogram or troponin rise	Death due to arterial or venous thromboembolism	2 years

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: International Society on Thrombosis and Haemostasis
• Investigators: Study Director: Cary Clark, International Society on Thrombosis and Haemostasis

Publications and helpful links

Helpful Links

• Case report form - DO NOT ENTER DATA WITHOUT OBTAINING CENTER NUMBER; links to study protocol, ethics approval; informed consent form

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: December 5, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Actual): December 12, 2022

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: stroke; myocardial infarction; hemorrhage; anticoagulation; vitamin K antagonist; antiaggregant
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Autoimmune Diseases; Immune System Diseases; Infarction; Necrosis; Myocardial Ischemia; Ischemia; Pathological Conditions, Signs and Symptoms; Stroke; Hemorrhage; Myocardial Infarction; Antiphospholipid Syndrome; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Purines; Phenols; Benzene Derivatives; Nucleosides; Ribonucleosides; Thiophenes; Salicylates; Hydroxybenzoates; Adenosine; Purine Nucleosides; Piperazines; Ticlopidine; Thienopyridines; Hematologic Agents; Ticagrelor; Clopidogrel; Prasugrel Hydrochloride; Aspirin; Platelet Aggregation Inhibitors
• Other Study ID Numbers: AATAAPS2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study protocol and ICF are available on the ISTH website (under SSC - RedCap. IPD will be shared after the primary publication.
• IPD Sharing Time Frame: Study protocol and ICF are available now and for 10 years after the end of the study. IPD will be available after the primary data have been published and for 10 years
• IPD Sharing Access Criteria: A research plan is required.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No