Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Saskia Middeldorp


Contact details

Academic Medical Centre
Department of Vascular Medicine
Meibergdreef 9
1105 AZ
+31 (0)20 5665976

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title


ALIFE - Anticoagulants for Living Foetuses

Study hypothesis

There is reasonable evidence to suggest that some cases of recurrent pregnancy loss (RPL), including recurrent miscarriage (RM) and/or later intra-uterine foetal death, are associated with placental thrombosis and infarction. Approximately 5% of women experience two or more consecutive pregnancy losses. Recurrent miscarriage, defined as two or more spontaneous first trimester pregnancy losses, may affect as many as 1% to 2% of women of reproductive age. The prognosis in subsequent pregnancies of women with RM or late foetal death is a rate of live birth of approximately 65% and 50%, respectively, without any therapeutic intervention. Some haematologic conditions, such as the antiphospholipid syndrome (APLS) are associated with RPL. Compared to controls, women with familial thrombophilia, especially those with combined defects or antithrombin deficiency, have an increased risk of RM (odds ratio: 1.35) and late foetal death (odds ratio: 3.6).

Heparin and low-dose aspirin have been shown to be effective and safe in reducing the pregnancy loss rate in patients with APLS, with significantly better pregnancy outcome than low dose aspirin alone. While several non-randomised studies have suggested that anticoagulant therapy in women with RPL with or without thrombophilia may be of benefit resulting in an increased live birth rate, strong evidence based on randomised controlled trials is still lacking. The aim of the present trial is to evaluate the efficacy of different anticoagulant therapies in women with RPL with or without thrombophilia.

Ethics approval

Ethics approval received from the local medical ethics committee

Study design

Randomised, double-blind, placebo controlled, parallel group trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Unexplained recurrent miscarriages, intra-uterine foetal death


After inclusion in the study, patients will be randomised to the following groups:
1. Placebo
2. Aspirin (carbasalate calcium) 100 mg/day
3. Aspirin (carbasalate calcium) 100 mg/day plus low dose LMWH subcutaneously (s.c.)

Placebo or low-dose aspirin is given from inclusion until 36 weeks of gestation. LMWH is given from 7 weeks gestation confirmed by foetal heartbeat throughout gestation.

Intervention type



Not Specified

Drug names

Aspirin, low-molecular-weight heparin

Primary outcome measures

Live birth rate

Secondary outcome measures

Prevalence of adverse pregnancy outcomes:
1. Pre-eclampsia
2. Haemolysis, elevated liver enzymes, low blood levels of platelets (HELLP) syndrome
3. Intra-uterine growth retardation
4. Premature delivery
5. Congenital malformations
6. Prevalence of thromboembolic and haemorragic complications
7. Thrombocytopaenia
8. Allergic reactions

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

Women with at least two unexplained miscarriages and/or intra-uterine foetal deaths

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Previous thromboembolism
2. Antiphospholipid syndrome (APLS)
3. Uterine abnormalities
4. Patients’ or their partners’ abnormal karyotype
5. Indication for anticoagulant treatment during pregnancy (for instance prosthetic heart valves)
6. Metabolic and toxic factors (diabetes mellitus, radiation exposure)
7. Known erythrocyte antibody anti-P syndrome
8. Pregnancy losses due to documented foetal malformation or the result of an infectious complication
9. Known allergy to at least three different low-molecular-weight heparin (LMWH) preparations
10. Previous inclusion in the ALIFE trial (for another pregnancy)

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Academic Medical Centre
1105 AZ

Sponsor information


Academic Medical Centre (AMC) (Netherlands)

Sponsor details

Department of Obstetrics and Gynaecology
Meibergdreef 9
1105 AZ

Sponsor type

Hospital/treatment centre



Funder type

Hospital/treatment centre

Funder name

Sanofi-Aventis (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Academic Medical Centre (AMC) (The Netherlands) - Department of Vascular Medicine and Department of Obstetrics and Gynaecology

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Viatris BV (The Netherlands) - manufacturer of carbasalate calcium

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2010 results in:
2014 results in:

Publication citations

  1. Results

    Kaandorp SP, Goddijn M, van der Post JA, Hutten BA, Verhoeve HR, Hamulyák K, Mol BW, Folkeringa N, Nahuis M, Papatsonis DN, Büller HR, van der Veen F, Middeldorp S, Aspirin plus heparin or aspirin alone in women with recurrent miscarriage., N. Engl. J. Med., 2010, 362, 17, 1586-1596, doi: 10.1056/NEJMoa1000641.

  2. Results

    Kaandorp SP, van Mens TE, Middeldorp S, Hutten BA, Hof MH, van der Post JA, van der Veen F, Goddijn M, Time to conception and time to live birth in women with unexplained recurrent miscarriage., Hum. Reprod., 2014, 29, 6, 1146-1152, doi: 10.1093/humrep/deu052.

Editorial Notes