Table 4 Summary of completed and ongoing clinical trials of the use of DOACs in APS. Adapted from references [32, 70,71,72,73,74,75,76]

RAPS (NCT02116036)

Prospective, controlled, phase 2/3, non-inferiority RCT

Primary or secondary thrombotic APS with previous isolated venous thromboembolism

Rivaroxaban 20 mg once daily

Warfarin (INR 2.0–3.0)

Endogenous thrombin potential (ETP)

Rivaroxaban did not reach the non-inferiority threshold

TRAPS (NCT02157272)

Phase 3, open-label, multicenter, non-inferiority RCT with blinded end-point

Triple positive thrombotic APS patients

Rivaroxaban 20 mg once daily (CrCl> 50) or 15 mg daily (if CrCl 30–50)

Warfarin (INR 2.0–3.0)

Cumulative incidence of thromboembolic events, major bleeding and vascular death

Terminated prematurely due to an excess of events in rivaroxaban arm

ASTRO-APS (NCT02295475)

Prospective, open-label, blinded event, phase 4 pilot RCT

Primary or secondary thrombotic APS. Exclusion: previous arterial events and recurrent venous thromboembolism when taking warfarin with INR of 2.0–3.0.

Apixaban 2.5 mg twice a day (increased to 5 mg twice a day + brain MRI after protocol modification)

Warfarin (INR 2.0–3.0)

Rates of thrombosis and deaths caused by thrombosis/ major bleeding plus clinically relevant non-major bleeding over 1 year

Protocol modification (2017): unanticipated excessive risk of arterial events during the first months in apixaban group.

ECD: December 2019.

Canadian RAPS (NCT02116036)

Pilot phase 4, open-label RCT

Primary or secondary thrombotic APS (history of arterial thrombosis allowed). Exclusion: arterial thrombosis or recurrent venous events while on anticoagulation.

Rivaroxaban 20 mg daily

None (single-arm)

Rates of venous and arterial thrombosis and rates of minor, major and fatal bleeding

Single-arm feasibility study;

Rates of thrombosis similar to warfarin studies

NCT02926170

Prospective, open-label, phase 3 RCT

APS patients with previous arterial events and recurrent thrombosis

Rivaroxaban 20 mg once daily (CrCl> 50) or 15 mg daily (if CrCl 30–50)

Acenocoumarol (INR 2.0 to 3.0 or 2.5 to 3.5 if recurrent thrombosis)

New thrombotic event or incidence of major bleeding (time frame: 36 months)

Rivaroxaban did not reach the non-inferiority threshold

RISAPS (NCT03684564)

Prospective, controlled, phase 2/3, non-inferiority RCT

Primary or secondary thrombotic APS with previous stroke or other ischemic brain manifestations

Rivaroxaban 15 mg twice a day

Warfarin (INR between 3.0–4.0)

Rate of chance in brain white matter hyperintensity volume on MRI (baseline and 24 months)

ECD: October 2022