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 |
| Protocol serial number | NTR206 |
| Sponsor | Academic Medical Centre (AMC) (Netherlands) |
| Funders | Sanofi-Aventis (The Netherlands), Academic Medical Centre (AMC) (The Netherlands) - Department of Vascular Medicine and Department of Obstetrics and Gynaecology, Viatris BV (The Netherlands) - manufacturer of carbasalate calcium |
- 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
Scientific
Academic Medical Centre
Department of Vascular Medicine, F4-276
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
| Phone | +31 (0)20 5665976 |
|---|---|
| alife@amc.uva.nl |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised, double-blind, placebo controlled, parallel group trial |
| Secondary study design | Randomised controlled trial |
| 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 |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Aspirin, low-molecular-weight heparin |
| Primary outcome measure(s) |
Live birth rate |
| Key secondary outcome measure(s) |
Prevalence of adverse pregnancy outcomes: |
| Completion date | 01/09/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target sample size at registration | 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
1105 AZ
Netherlands
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | 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 |
