Low molecular weightheparin (Fragmin) in pregnant women with a history of uteroplacentalinsufficiency and thrombophilia, a randomized trial
See also FRUIT study on the NVOG website
Aim of the study
Primary: Does preventive treatment with low-molecular-weight heparinreduce the occurrence of preeclampsia in women with thrombophilia and ahistory of preeclampsia before 34 weeks of pregnancy.
Secondary: A reduction of recurrence of small for gestational ageinfants in women with a history of small for gestational age infantsbefore 34 weeks and thrombophilia.
Multi-center open two-armed randomized study.
The recurrence rate of preeclampsia is 35% and small for gestationalage infants 21% as recently studied in a Dutch population with a priorpregnancy with severe early onset preeclampsia or small for gestationalage infants (before 34 weeks gestation) and coagulation abnormalities,being treated with or without low-molecular-weight heparin and aspirin.
To detect a 50% reduction from 35% recurrence rate of preeclampsia 262patients will be randomized, aiming for 131 + 131 patients in the 2arms of the study (2-tailed, an alpha of 0.05 and a power of 80%).Recurrence rate of uteroplacental insufficiency in women withantiphospholipid antibodies is 60%. To detect a 50% reduction from 60%recurrence rate of uteroplacental insufficiency 84 patients will berandomized, aiming for 42 + 42 patients in the 2 arms of the study(2-tailed, an alpha of 0.05 and a power of 80%).
The verum group will receive low-molecular weight heparin (Fragmin,subcutaneously 1 x 5000 IU AXA per day) + low dose acetylsalicylacid(ASA 80mg). Fragmin is started as early as possible between six andtwelve weeks gestation, after ultrasound confirmation of a viableintrauterine pregnancy. Fragmin will be continued until six weeks postpartum. ASA is given from 12 weeks gestation till 36 weeks gestation.The control group will receive ASA and standard care that is normallygiven to these high-risk pregnancies.
Differences between the groups treated with low-molecular weightheparin and aspirin versus aspirin only will be assessed, accountingfor prognostic factors, with the Mantel-Haenszel method or withlogistic regression. Quantitative analysis will be assessed with linearregression.
Download here the FRUIT protocol - version 20-01-2000.