Condition category
Pregnancy and Childbirth
Date applied
20/12/2005
Date assigned
20/12/2005
Last edited
09/04/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 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

01/02/2004

Overall trial end date

01/09/2008

Reason abandoned

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

http://www.amc.uva.nl/

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

Results - basic reporting

Publication summary

2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20335572
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24682612

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.

Additional files

Editorial Notes