Low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy: Rationale and design of the Highlow study, a randomised trial of two doses. Issue 144 (August 2016)

• Record Type: Journal Article
• Authors: Bleker, Suzanne M.; Buchmüller, Andrea; Chauleur, Céline; Áinle, Fionnuala Ní; Donnelly, Jennifer; Verhamme, Peter; Jacobsen, Anne Flem; Ganzevoort, Wessel; Prins, Martin; Beyer-Westendorf, Jan; DeSancho, Maria; Konstantinides, Stavros; Pabinger, Ingrid; Rodger, Marc; Decousus, Hervé; Middeldorp, Saskia
• Is Part Of: Thrombosis research. Issue 144(2016)
• Page Start: 62
• Page End: 68
• Publication Date: 2016-08
• Subjects: Prophylaxis -- Pregnancy -- Venous thrombosis -- Clinical trials -- LMWH; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2016.06.001
• Languages: English
• ISSNs: 0049-3848

Abstract

Summary: Background: Women with a history of venous thromboembolism (VTE) have a 2% to 10% absolute risk of VTE recurrence during subsequent pregnancies. Therefore, current guidelines recommend that all pregnant women with a history of VTE receive pharmacologic thromboprophylaxis. The optimal dose of low-molecular-weight heparin (LMWH) for thromboprophylaxis is unknown. In the Highlow study (NCT 01828697;www.highlowstudy.org ), we compare a fixed low dose of LMWH with an intermediate dose of LMWH for the prevention of pregnancy-associated recurrent VTE. We present the rationale and design features of this study. Methods: The Highlow study is an investigator-initiated, multicentre, international, open-label, randomised trial. Pregnant women with a history of VTE and an indication for ante- and postpartum pharmacologic thromboprophylaxis are included before 14 weeks of gestation. The primary efficacy outcome is symptomatic recurrent VTE during pregnancy and 6 weeks postpartum. The primary safety outcomes are clinically relevant bleeding, blood transfusions before 6 weeks postpartum and mortality. Patients are closely monitored to detect cutaneous reactions to LMWH and are followed for 3 months after delivery. A central independent adjudication committee adjudicates all suspected outcome events. Conclusion: The Highlow study is the first large randomised controlled trial in pregnancy that will provide high-quality evidence on the optimal dose of LWMH thromboprophylaxis for the prevention of recurrent VTE in pregnant women with a history of VTE. Highlights: Pregnant women with a history of VTE have a high risk of recurrent VTE. The optimal dose of LMWH for thromboprophylaxis ante- and postpartum is unknown. The Highlow study randomizes to a fixed low dose or an intermediate dose of LMWH. The primary efficacy outcome is recurrent symptomatic VTE up to 6 weeks postpartum. The primary safety outcomes are clinically relevant bleeding and mortality.