Low-dose aspirin versus placebo in postpartum venous thromboembolism: a multi-national, pilot, randomised, placebo-controlled trial.

Abstract

BACKGROUND Despite the morbidity and mortality of venous thromboembolism, there is little evidence to guide postpartum thromboprophylaxis in patients at moderate risk. We aimed to assess the feasibility of conducting a double-blind, randomised trial of aspirin versus placebo in postpartum individuals with two or more venous thromboembolism risk factors, mild-to-moderate thrombophilia, or both. METHODS The pilot PARTUM trial, a multi-national, randomised, double-blind, placebo-controlled trial, was conducted in seven centres across Canada, France, Ireland, and the Netherlands. Postpartum individuals aged 18 years or older with venous thromboembolism risk factors, including mild-moderate inherited thrombophilia, antepartum immobilisation, pre-pregnancy BMI of 30 kg/m2 or higher, pre-pregnancy smoking, previous superficial vein thrombosis, and other pregnancy-related conditions, were eligible. Participants were randomly assigned (1:1) within 48 h of delivery to aspirin 81 mg (80 mg in Europe) orally daily (low-dose aspirin group) or placebo orally once daily (placebo group) for 42 days. Follow-up visits occurred at 6 weeks and 90 days postpartum. The primary outcome was the mean recruitment rate (participants per site per month). Additional feasibility metrics were reported, and clinical outcomes were analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT04153760, and EudraCT, 2020-000619-58, and is completed. FINDINGS Between Nov 2, 2020, and June 19, 2023, 10 040 patients were assessed for eligibility and 808 met all eligibility criteria, of whom 257 (32%) provided consent and were enrolled. 127 were randomly assigned to the low-dose aspirin group and 130 to the placebo group. The median follow-up was 91 days (IQR 89-96). The median age was 34·0 years (IQR 30·0-37·0), and 161 (63%) of participants were White. The mean recruitment rate was 6·3 (95% CI 5·5 to 7·2) patients per site per month. No venous thromboembolism events occurred in the low-dose aspirin group, and one participant had distal deep vein thrombosis in the placebo group (-0·82 [95% CI -2·42 to 0·78]). No major bleeds occurred. Three (2%) participants in the low-dose aspirin group versus one (1%) in the placebo group had clinically relevant non-major bleeds (absolute risk difference 1·66 [95% CI -1·54 to 4·86]). Ten serious adverse events occurred in nine (4%) of 257 participants, and 11 serious adverse events occurred in ten (4%) of 271 infants of participants. No treatment-related death occurred. INTERPRETATION A global postpartum thromboprophylaxis trial evaluating low-dose aspirin is possible and needed to provide high-quality data. FUNDING Canadian Institutes of Health Research and the INVENT-VTE Network.