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
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
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
1105 AZ
Netherlands
Sponsor information
Academic Medical Centre (AMC) (Netherlands)
Hospital/treatment centre
Hospital/treatment centre
Department of Obstetrics and Gynaecology
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
Website | http://www.amc.uva.nl/ |
---|---|
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 |