Laskin 2009.

Study characteristics
Methods	Open‐label randomised controlled trial (N = 88). Subgroup with aPL antibodies N = 42
Participants	Inclusion criteria 1) aged 18 to 44 years at time of randomisation 2) history of ≥ 2 unexplained consecutive pregnancy losses prior to 32 weeks' gestation 3) presence of at least 1 of the following: ANA, antiphospholipid antibodies (aCL IgG > 15 GPL or IgM > 25 MPL and/or LAC positivity, tested on 2 occasions at least 8 weeks apart), or an inherited thrombophilia 4) confirmed pregnancy by either 2 appropriately rising quantitative beta human chorionic gonadotropin (beta hCG) tests performed 48 hours apart or by ultrasound confirming fetal heart activity Exclusion criteria Systemic lupus erythematosus (fulfilling American College of Rheumatology classification criteria), known peptic ulcer disease (within the last 5 years), sensitivity to aspirin or heparin obtained by self‐report, bone mineral density z score <‐ 2.5, known platelet function abnormality, previous thromboembolic event requiring ongoing anticoagulant therapy including heparin/aspirin/warfarin verified in medical records, genetic/anatomic/hormonal aetiology for pregnancy loss was identified by (respectively) karyotype analysis of both partners, hysterosalpingogram/sonohysterogram, and a hormonal evaluation (which included either an endometrial biopsy or loss while taking progesterone or clomiphene therapy or mid luteal phase serum progesterone levels timed appropriately), geographic distance from the clinic and hospitals in Toronto/Hamilton, failure to consent.
Interventions	LMWH (dalteparin) 5000 U/day sc + aspirin 81 mg/day (N = 22) versus Aspirin 81 mg/day (N = 20)
Outcomes	Live birth
Notes	42 of 88 randomised participants had persistent presence of antiphospholipid antibodies, of whom 22 were randomised to LMWH + aspirin and 20 were randomised to aspirin alone. Aspirin and LMWH started at randomisation (after confirmed pregnancy) and continued until 35 weeks of gestation. Authors have been contacted to provide information on the secondary outcomes for the subgroup of aPL‐positive participants 32/45 in the LMWH + aspirin group had a history of early losses (≤ 14 weeks of gestation) versus 34/43 in the aspirin group. 4/45 in the LMWH + aspirin group had a still birth (20‐32 weeks of gestation) versus 7/43 in the aspirin group. Pregnancy loss in 10/45 in the LMWH + aspirin group (7/10 ≤ 14 weeks of gestation, 2/10 ectopic pregnancy, 1 stillbirth) versus 9/43 in the aspirin group (8/9 ≤ 14 weeks of gestation, 1 stillbirth). Trial registry: study registered at clinicaltrials.gov [NCT 00564174] Dates of study: recruitment period 2000‐2004, publication in 2009. Funding sources: Canadian Institute of Health Research (CIHR) Rx&D grant (PCT 37749) and by a grant from Pfizer Canada (formerly Pharmacia, Canada). LMWH was supplied by Pfizer Canada. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central randomisation. Stratified by presence or absence of aPL, and early (≤ 14 weeks) versus late (15‐32 weeks) losses. Women with history of both early and late losses were assigned to the late stratum.
Allocation concealment (selection bias)	Low risk	Adequate allocation concealment; central randomisation, communication by telephone.
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	Low risk	Exclusions, reasons for exclusion and numbers included in the analysis at each stage were reported; no loss to follow‐up, all participants analysed.
Selective reporting (reporting bias)	Low risk	Study registered at clinicaltrials.gov [NCT 00564174]. All of the study's pre‐specified outcomes and all expected outcomes of interest were reported.
Other bias	Low risk	Multicentre trial (2 centres).