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ALIFE2 study

 

Go to the ALIFE2 website.

 

Anticoagulants for living fetuses in women with recurrent miscarriage and inherited thrombophilia


Objective
The primary objective of the ALIFE2 study is to evaluate the efficacy of low molecular weight heparin (LMWH) in women with recurrent miscarriage (RM) and inherited thrombophilia. Secondary objectives are to evaluate other possible effects of LMWH on adverse pregnancy outcome other than miscarriage (e.g. preeclampsia, intra-uterine growthrestriction, HELLP syndrome, placental abruption, premature delivery, congenital malformations) as well as to evaluate the safety of LMWH in women with RM with inherited thrombophilia by registering complications such as haemorrhage, thrombocytopenia and (allergic) skin reactions.

Study design
International multicenter randomized controlled trial.
Women with a history of RM (2 or more not necessarily consecutive miscarriages), confirmed inherited thrombophilia and who are attempting to conceive or are less than 7 weeks pregnant will be recruited for the study. As soon as a urine pregnancy test is positive, they will be randomised to one of two groups. Women in group 1 will inject LMWH once daily, starting immediately after randomisation. To avoid peripartum hemorrage, LMWH will be discontinued at the beginning of labour. Women in group 2 will receive no intervention in addition to standard pregnancy surveillance.

Study population
Women, aged 18-42 at randomisation, with a history of two or more miscarriages with confirmed inherited thrombophilia, who are actively trying to conceive or less than 7 weeks pregnant will be recruited for the study.
The research population will be drawn from women with a history of RM and a positive test for either factor V Leiden, prothrombin gene mutation (G20210A), antithrombin deficiency, protein C deficiency or protein S deficiency, or a combination hereof.
Recruitment will take place in the Netherlands, as well as in several other countries, to be determined.

Intervention
Women randomized to the intervention arm of the study will receive LMWH, once daily, in a dose comparable to the prophylactic dose used after orthopedic surgery. Women randomized to the no-treatment arm will receive standard pregnancy surveillance.

Outcome measures
The primary outcome measure of this objective is live birth in each treatment group. Secondary outcome measures include adverse pregnancy outcomes (e.g. pre-eclampsia, HELLP syndrome, intra-uterine growth restriction, placental abruption, premature delivery, congenital malformations) and adverse effects of treatment (hemorrhagic episodes, thrombocytopenia and(allergic) skin reactions to LMWH).

Power/data analysis
In the previous ALIFE study (Kaandorp, NEJM 2010), the occurrence of live birth in the subgroup of women who had an abnormal thrombophilia test and who became pregnant was 60% in those who were randomized to placebo. Based on this information, a conservative sample size assuming a live birth of 55% in the no treatment group is calculated. In order to detect an absolute risk difference of 15%, with a power of 80% and a two-sided confidence level of 95% (P<0.05), the sample size required for the study will be n=332, with in each arm 166 women. Taking a potential loss to follow up and exclusion from the study (due to ectopic pregnancy for example) into consideration, we aim to recruit 20% more women (n=399).

Time schedule
Start of recruitment: December 2012
Planned duration of the study: three years

Projectleaders
prof. dr. S. Middeldorp, internist, Academic Medical Center, Amsterdam
dr. M. Goddijn,gynecologist, Academic Medical Center, Amsterdam

Methodology
dr. B.A. Hutten, epidemiologist, Academic Medical Center, Amsterdam

Subsidy
ZonMW VIDI grant
 
Contact (researcher)

Luuk Scheres, MD
Ph D student / investigator ALIFE2 study
Academic Medical Center, University of Amsterdam
Meibergdreef 9
1105 AZ Amsterdam, the Netherlands
P: +31 20 5662377/+31 71 5265635