Contact information
Type
Scientific
Primary contact
Dr Saskia Middeldorp
ORCID ID
Contact details
Academic Medical Centre
Department of Vascular Medicine
F4-276
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
+31 (0)20 5665976
alife@amc.uva.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NTR206
Study information
Scientific title
Acronym
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
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
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
Phase
Not Specified
Drug names
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 trial start date
01/02/2004
Overall trial end date
01/09/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Women with at least two unexplained miscarriages and/or intra-uterine foetal deaths
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
300
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
01/02/2004
Recruitment end date
01/09/2008
Locations
Countries of recruitment
Netherlands
Trial participating centre
Academic Medical Centre
Amsterdam
1105 AZ
Netherlands
Sponsor information
Organisation
Academic Medical Centre (AMC) (Netherlands)
Sponsor details
Department of Obstetrics and Gynaecology
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Sanofi-Aventis (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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
Location
Funder name
Viatris BV (The Netherlands) - manufacturer of carbasalate calcium
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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
Basic results (scientific)
Publication list
2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20335572
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24682612
Publication citations
-
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.
-
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.