SINGLE-AF Trial Design: Intentional 1:1 Randomization with Open-Label Allocation
The SINGLE-AF trial was designed as a 1:1 randomized trial with 902 patients assigned to DOAC therapy and 901 to no anticoagulation—this equal allocation was intentional, and the trial was explicitly open-label (unmasked) with blinded outcome adjudication 1, 2.
Trial Design Specifications
The SINGLE-AF study protocol clearly describes this as an "investigator-initiated, multicenter, open-label, superiority, randomized trial with blinded outcome assessment" 2. The randomization scheme was:
- 1:1 allocation ratio between DOAC therapy and no anticoagulation 1, 2
- Final enrollment: 902 patients in DOAC group vs. 901 in no-anticoagulation group 1
- This near-perfect balance (difference of only 1 patient) confirms the intentional equal allocation design
Open-Label Design Rationale
The open-label nature was intentional and necessary because:
- You cannot blind patients to whether they are taking anticoagulation or not—this is a practical impossibility in comparing active treatment versus no treatment
- The trial maintained scientific rigor through adjudicator masking: outcome assessors were blinded to treatment allocation when evaluating endpoints 1, 2
- This design (open-label with blinded endpoint adjudication) is standard methodology for trials comparing active treatment versus no treatment
Key Design Features
The trial evaluated:
- Population: AF patients with CHA₂DS₂-VASc score of 1 (men) or 2 (women)—intermediate stroke risk 1, 2
- Intervention: Direct oral anticoagulants (apixaban or rivaroxaban) 2
- Comparator: No anticoagulation therapy 1, 2
- Primary endpoint: Composite of stroke, systemic embolism, major bleeding, and cardiovascular death at 24 months 1, 2
Important Methodological Note
If you observed a discrepancy in group sizes in any presentation of the data, this likely reflects:
- Differential dropout or loss to follow-up (not reported as significant in the main results)
- Subgroup analyses that may have excluded certain patients
- The baseline randomization was definitively 1:1 as designed
The trial successfully demonstrated DOAC superiority (primary endpoint: 0.5% vs. 1.5%, HR 0.31,95% CI 0.10-0.94, P=0.03) 1, providing the first randomized evidence for anticoagulation in this intermediate-risk population.