Kutteh 1996b.

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 documented pregnancy losses 4) Presence of antiphospholipid antibodies IgG ≥ 27 GPL (> 2.5 multiples of the median) on 2 separate occasions 5) Consent to treatment protocol Exclusion criteria Systemic lupus erythematosus, a positive test for lupus anticoagulant, an allergy to aspirin, a documented bone disorder, another abnormal test result that was not corrected aspirin allergy, refused treatment.
Interventions	Aspirin 81 mg/day plus heparin 5000 U twice daily sc adjusted to maintain the PTT at 1.2 to 1.5 times the baseline (high dose) (N = 25) versus Aspirin 81 mg/day + heparin 5000 U twice daily sc adjusted to maintain the PTT at the upper limit of normal (low dose) (N = 25)
Outcomes	Obstetric complications (preterm birth, intrauterine growth retardation and maternal complications (gestational diabetes, major and minor bleeding, thrombocytopenia, pre‐eclampsia)
Notes	Mean daily dose in low‐dose heparin group 8127 ± 2389 U twice daily; mean daily dose in high‐dose heparin group 13300 ± 3500 U twice daily. Aspirin commenced before conception, heparin commenced at the first confirmed pregnancy test. Treatment was continued until delivery and heparin continued for 3 weeks postpartum. Mean total prior miscarriages per patient was 3.6 ± 1.0 in the low‐dose UFH + aspirin group (92.9% of these < 20 weeks of gestation) versus 3.9 ± 1.4 in the aspirin group (91.2% of these < 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
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	The first 25 women had heparin dosages adjusted periodically to maintain the baseline PTT at 1.2 to 1.5 times baseline (HD heparin). The second 25 women had heparin dosages adjusted periodically to maintain the PTT at the allocated to upper limits of the normal range (LD heparin).
Allocation concealment (selection bias)	High risk	No concealment of allocation.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding not reported, but knowledge of treatment allocation unlikely to influence outcome live birth.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding not reported, but knowledge of treatment allocation unlikely to influence outcome live birth.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Over 750 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 any other source of bias.