The death of a mother is a tragedy with far-reaching consequences. Pregnancy-relatedvenous thromboembolism (VTE) remains a leading causes of maternal deathin western countries including Ireland. Pregnant women with prior VTE have a highrisk of recurrence. Therefore, thromboprophylaxis with low-molecular-weight-heparin (LWMH) is indicated. Potentially fatal recurrent VTE occurs despitethromboprophylaxis. International guidelines suggest one of two LMWH doses toprevent recurrence. However, the precise optimal doseremains unknown. This poses major challenges in the management of pregnantmothers who are at high risk of a dangerous complication. In Ireland, astaggering 160 pregnant women experienced VTE in 2012.
The HIGHLOW study will evaluate the efficacy and safety of intermediate doseversus low dose LMWH in pregnant women with a history of previous VTE.HIGHLOW is a multicentre, international randomized controlled trial led by international leader and co-PI Prof. Saskia Middeldorp.
The Lead Applicant is currently PI for this important trial in Ireland at one tremendously successful pilot Irish site.We now request funding toscale this up to include 6 Irish sites. In total, we estimate thatIreland will contribute a third of all patients to this international study. With the international team, the Lead Applicant and Co-applicant Dr Donnelly have already co-authored an international publication on the HIGHLOW trial protocol. It is predicted that the final study will be viewed as a landmark publication in a very high-impact journal.
The trial will be supportedby the wealth of experience of the HRB Ireland Perinatal Clinical Trials Network.As a team, the PIs and collaborators have a strong track record in the managementof high quality clinical research including randomized controlled trials (RCTs). Pregnant women are usually excluded from clinical trials and despite the terriblepotential consequences, good quality evidence is frequently lacking. Internationalpolicymakers have recently called for urgent action to address this critical issue. Thisapplication has received support letters from international leaders in the fieldincluding Prof. Ian Greer.
In summary, the HIGHLOW study addresses an urgent need in Irish and internationalhealthcare, for the benefit of our pregnant mothers and their familes.
