To evaluate the efficacy of low molecular weight heparin (LMWH) in women with inherited thrombophilia and recurrent miscarriage on live birth.
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
- Abortions and stillbirth
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy outcome is live birth in each treatment group.
Secondary outcome
Secondary efficacy outcome measures are prevalence of adverse pregnancy
outcomes, such as miscarriage rates, pre-eclampsia, the syndrome of haemolysis,
elevated liver enzymes en low platelets (HELLP-syndrome), intrauterine growth
restriction, placental abruption, premature delivery and congenital
malformations.
Safety outcomes are thrombocytopenia, hemorrhagic episodes and skin reactions
to the prescribed study medication.
Background summary
In all clinically recognized pregnancies, a single spontaneous miscarriage
occurs in 14-19% of patients, and 1-5% of women experience two or more
miscarriages (recurrent miscarriage). In over 50% of cases of miscarriage the
cause remains unexplained. Many studies have confirmed a relationship between
inherited thrombophilia and miscarriage and other pregnancy complications. The
role of thrombophilia in recurrent miscarriage can be explained partially by
the concept of thrombosis of the (microvasculature of the) placenta, and
partially because of inhibition of extravillous trophoblast differentiation.
Therefore, anticoagulants are considered a possible therapy for women with
recurrent miscarriage and inherited thrombophilia.
Beneficial effects of anticoagulants (low molecular weight heparin with or
without aspirin) for women with unexplained recurrent miscarriage were reported
in several studies. However, these studies were either not randomized, not
placebo-controlled, or had other methodological limitations. Recently, the
results of three RCT's (ALIFE study, SPIN study and Habenox study) showed that
treatment with low molecular weight heparin with or without aspirin does not
improve the chance of live birth in women with unexplained recurrent
miscarriage. Neither the ALIFE-study, nor the SPIN-study, nor the Habenox study
was sufficiently powered to demonstrate an effect of pharmacological therapy in
the subgroup of women with inherited thrombophilia. Pregnancy failure is
severely distressing for couples who desire to have children. As can be
concluded from the above written; there is an urgent need for randomized,
adequately designed trials on the use of anticoagulants in women with recurrent
miscarriage and inherited thrombophilia.
Study objective
To evaluate the efficacy of low molecular weight heparin (LMWH) in women with
inherited thrombophilia and recurrent miscarriage on live birth.
Study design
Randomized intervention study of LMWH plus standard pregnancy surveillance vs.
standard pregnancy surveillance alone.
Intervention
The subjects will be randomly assigned to receive LMWH plus standard pregnancy
surveillance or standard pregnancy surveillance alone.
Study burden and risks
The administration of LMWH is considered to be safe in healthy human subjects,
as well as in pregnant women. However, there are possible adverse effects.
Potential risks include maternal or fetal bleeding, heparin induced
thrombocytopenia and heparin induced osteoporosis. Subjects will receive
standard surveillance care provided by their own obstetrician throughout
pregnancy, including structural fetal ultrasonography.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
-Women with recurrent miscarriage (>= 2) and/or intra-uterine fetal deaths (i.e. >= 2 miscarriages of intra-uterine fetal deaths, irrespective of gestational age;
-Confirmed inherited thrombophilia; factor V Leiden mutation, prothrombin gene mutation (G20210A), protein S deficiency, protein C deficiency or antithrombin deficiency or a combination hereof. Protein S, -C and antithrombin deficiencies need to be confirmed by two independent tests, performed on two separate occasions and not during pregnancy or anticoagulant therapy;
-Pregnancy confirmed by urine pregnancy test;
-Age 18 - 42 years at randomisation;
-Willing and able to give informed consent;
Exclusion criteria
-Duration of current pregnancy >= 7 weeks; based on first day of last menstruation.
-Indication for anticoagulant treatment during pregnancy (for instance prosthetic heart valves, a history of venous thromboembolism or antiphospholipid syndrome);
-Contraindications to LMWH (previous heparin induced thrombocytopenia, active bleeds or renal insufficiency with creatinine clearance of less than 30ml/min);
-Known allergy to at least 3 different LMWH preparations;
-Previous inclusion in the ALIFE2 study (for another pregnancy);
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-001447-43-NL |
| CCMO | NL40256.018.12 |