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 design	Randomised, double-blind, placebo controlled, parallel group trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title
Study acronym	ALIFE - Anticoagulants for Living Foetuses
Study objectives	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(s)	Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studied	Unexplained recurrent miscarriages, intra-uterine foetal death
Intervention	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	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Aspirin, low-molecular-weight heparin
Primary outcome measure	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 study start date	01/02/2004
Completion date	01/09/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target number of participants	300
Key inclusion criteria	Women with at least two unexplained miscarriages and/or intra-uterine foetal deaths
Key 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)
Date of first enrolment	01/02/2004
Date of final enrolment	01/09/2008

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"	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 share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not 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