Pulmonary embolism (PE), the most serious form of venous thromboembolism (VTE), is a leading cause of maternal mortality in the developed world. Maternal mortality is a devastating event with far-reaching emotional, social and economic implications. Symptomatic VTE is estimated to occur antepartum in 5-12 per 10,000 pregnancies, and to occur postpartum in 3-7 per 10,000 deliveries. Compared with age-matched, non- pregnant controls, this translates into a per day risk that is increased 7-10 fold for antepartum VTE, and 15-35 fold for postpartum VTE. Hence, the postpartum period is the period of greatest risk. The important question of how best to prevent pregnancy-related VTE remains unanswered, in part because it has been difficult to identify otherwise young and otherwise healthy women who are at high risk for VTE. However, a recent large, well-conducted case control study identified risk factors in postpartum women, including factors, when combined, which resulted in multiplicative effect. Based on these data, we can define a group of women with OR >10 for post-partum VTE. We hypothesize that targeted VTE prophylaxis in the early post-partum period will result in a significant decrease in symptomatic deep vein thrombosis (DVT) and PE and asymptomatic proximal DVT. Targeted post-partum prophylaxis could impact >25% of deliveries in the U.S. and Canada and significantly change obstetric care. A randomized trial to assess the efficacy of VTE prophylaxis in this setting is needed. Important questions regarding the feasibility of such a trial need to be addressed prior to embarking on a definitive trial. This application outlines a feasibility study with the following Specific Aims: 1) To enroll women at risk (OR>10) of post-partum VTE, without other indications for VTE prophylaxis, in a randomized controlled trial of prophylactic LMWH versus placebo, beginning within 36 hours post-partum and continuing for 3 weeks at 3 participating institutions, 2) To assess our prediction that at least 30% of eligible women approached will agree to enroll, at least 80% of women will comply with study drug injections, and at least 90% will have an evaluable ultrasound at end of study, 3) To assess the acceptance of a placebo injection arm in this setting, and 4) To finalize a multi-center trial based on the findings of this pilot/feasibility study.

Public Health Relevance

Venous thromboembolism (VTE) including deep venous thrombosis and pulmonary embolism are major contributors to maternal morbidity and mortality in the U.S. This study aims to determine the feasibility of a trial to assess low molecular weight heparin prophylaxis in this setting, in order to decrease the incidence of post-partumVTE and associated illness and death.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Planning Grant (R34)
Project #
5R34HL107725-02
Application #
8288722
Study Section
Clinical Trials Review Committee (CLTR)
Program Officer
Kindzelski, Andrei L
Project Start
2011-07-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2012
Total Cost
$300,699
Indirect Cost
$50,446
Name
Puget Sound Blood Center
Department
Type
DUNS #
092881085
City
Seattle
State
WA
Country
United States
Zip Code
98104