Kutteh 1996a.

Study characteristics
Methods	Single‐centre, quasi‐randomised, non‐blinded, non‐placebo controlled trial (N = 50)
Participants	Inclusion criteria 1) Desire to become pregnant 2) Agreement to be completely evaluated 3) ≥ 3 spontaneous consecutive miscarriages 4) Consent to alternative treatment assignment 5) Presence of antiphospholipid antibodies ≥ 27 IgG or ≥ 23 IgM phospholipid units (> 2.5 multiples of the median) on 2 separate occasions Exclusion criteria Systemic lupus erythematosus, positive for lupus anticoagulant, presence of another abnormal test result that was not corrected either medically or surgically, aspirin allergy, another reason for anticoagulation during pregnancy, refused treatment or assignment to treatment.
Interventions	Unfractionated heparin 5000 units sc twice daily + aspirin 81 mg/day (N = 25) versus Aspirin 81 mg/day (N = 25)
Outcomes	Obstetric complications (preterm birth, intrauterine growth retardation and maternal complications (gestational diabetes, major and minor bleeding, thrombocytopenia, pre‐eclampsia)
Notes	Aspirin commenced before conception, heparin commenced at the first confirmed pregnancy test (5.3 weeks post‐gestation). Treatment was continued until delivery and heparin continued for 3 weeks postpartum. Heparin dose increased by 1000 units/dose weekly until PTT was 1.2‐1.5 times baseline. Mean total prior miscarriages per patient was 3.9 ± 1.4 in the UFH + aspirin group (79.1% of these < 12 weeks of gestation, 91.3% < 20 weeks of gestation) versus 3.7 ± 1.0 in the aspirin group (76.6% of these < 12 weeks of gestation, 88.5% < 20 weeks of gestation). As study outcome total pregnancy loss reported; no specification for early and late loss reported. Trial registry: trial not registered in clinical trial registry, but clinical trial registry at time of publication non‐existing. No published study protocol. Dates of study: recruitment period not specified, publication in 1996. Funding sources: not stated Declarations of interest: not stated Authors report that treatment was initiated at the first documented pregnancy test, to eliminate selection bias.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Non‐random alternative assignment of treatment.
Allocation concealment (selection bias)	High risk	No concealment of allocation.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	No blinding, but knowledge of treatment allocation unlikely to influence outcome live birth.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	No blinding, but knowledge of treatment allocation unlikely to influence outcome live birth.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	600 women evaluated, 50 consented to study participation; exclusions, reasons for exclusion and numbers included in the analysis at each stage were not reported. Unclear whether all evaluated participants started low‐dose aspirin before conception, prior to randomisation. Analysis by intent‐to‐treat and loss to follow‐up unclear.
Selective reporting (reporting bias)	Unclear risk	Trial not registered in clinical trial registry, but clinical trial registry at time of publication non‐existing, therefore unclear risk. No published study protocol.
Other bias	Low risk	No indication of other sources of bias