The HABIT: Heparin and Aspirin on Birth in Inherited Thrombophilia, an International Multicenter Phase IIb Randomized Triple Blinded Clinical Trial

Abstract

Background/Objective: In pregnant women with inherited thrombophilia (IT) and recurrent pregnancy loss, there is no higher-level evidence proving the beneficial effects of anticoagulation or platelet inhibition in preventing miscarriages. We hypothesize that anticoagulation with low molecular weight heparin (LMWH) and/or platelet aggregation inhibition with aspirin will increase the proportion of live birth in this population. Methods: In this phase IIb, factorial, randomized, triple blinded, placebo-controlled (double dummy) clinical trial, pregnant women age 18 to 40 with a history of IT and 2 or more previous miscarriages will be randomized and stratified by age and number of miscarriages in a 2x2 factorial design will be allocated equally to one of the four arms. The primary outcome of live birth will be analyzed through logistic regression analysis, controlling for strata, and results will be reported as odds ratio (OR) and 95% confidence intervals (CIs). Analyzed similarly, the secondary outcomes will include pregnancy loss, maternal mortality, major bleeding events, medication-associated adverse events, placental abruption, preterm birth, and gestational age at delivery. We will perform subgroup analysis for smoking status, weight, age, number of miscarriages, and type of thrombophilia. Discussion: There is lack of evidence for the use of anticoagulants to prevent pregnancy loss in women with inherited thrombophilia, despite the common diverging prescribing practice predominantly extrapolated from observations in acquired thrombophilia. With this study, we aim to provide an evidence base to create a standard of care in cases of recurrent pregnancy loss in women with IT. Keywords: heparin; aspirin; inherited thrombophilia; pregnant; live birth