Aspirin and/or low-molecular weight heparin for women with unexplained recurrent miscarriages and/or intra-uterine foetal death

ISRCTN ISRCTN58496168
DOI https://doi.org/10.1186/ISRCTN58496168
Secondary identifying numbers NTR206
Submission date
20/12/2005
Registration date
20/12/2005
Last edited
09/04/2014
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Pregnancy and Childbirth
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Saskia Middeldorp
Scientific

Academic Medical Centre
Department of Vascular Medicine, F4-276
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Phone +31 (0)20 5665976
Email alife@amc.uva.nl

Study information

Study designRandomised, double-blind, placebo controlled, parallel group trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific title
Study acronymALIFE - Anticoagulants for Living Foetuses
Study objectivesThere 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(s)Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studiedUnexplained recurrent miscarriages, intra-uterine foetal death
InterventionAfter 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Aspirin, low-molecular-weight heparin
Primary outcome measureLive birth rate
Secondary outcome measuresPrevalence 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 study start date01/02/2004
Completion date01/09/2008

Eligibility

Participant type(s)Patient
Age groupAdult
SexFemale
Target number of participants300
Key inclusion criteriaWomen with at least two unexplained miscarriages and/or intra-uterine foetal deaths
Key exclusion criteria1. 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)
Date of first enrolment01/02/2004
Date of final enrolment01/09/2008

Locations

Countries of recruitment

  • Netherlands

Study participating centre

Academic Medical Centre
Amsterdam
1105 AZ
Netherlands

Sponsor information

Academic Medical Centre (AMC) (Netherlands)
Hospital/treatment centre

Department of Obstetrics and Gynaecology
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Website http://www.amc.uva.nl/
ROR logo "ROR" https://ror.org/03t4gr691

Funders

Funder type

Hospital/treatment centre

Sanofi-Aventis (The Netherlands)

No information available

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

No information available

Viatris BV (The Netherlands) - manufacturer of carbasalate calcium

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 29/04/2010 Yes No
Results article results 01/06/2014 Yes No