HYPATIA: A prospective randomised controlled trial of hydroxychloroquine to improve pregnancy outcome in women with antiphospholipid antibodies
| ISRCTN | ISRCTN19920789 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN19920789 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | 2016-002256-25 |
| Protocol serial number | 8.1, CPMS 37234 |
| Sponsor | Guy's and St Thomas' NHS Foundation Trust |
| Funders | Research for Patient Benefit Programme, Guy's and St Thomas' Charity |
- Submission date
- 26/08/2020
- Registration date
- 27/08/2020
- Last edited
- 12/09/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims
Antiphospholipid syndrome (APS) is the combination of persisting antiphospholipid antibodies (aPL) and a previous thrombosis (blood clot) and/or pregnancy problems. Antibodies are part of the immune system, and can sometimes be directed against part of our own cells, this is known as autoimmune disease, and APS is such a problem. aPL occur in about 1% of the population, so extrapolating this to a birth rate of 800,000/year in the UK, this means 8,000 women with aPL are giving birth every year.
Women with aPL (this term includes those with APS) are more likely to have pregnancy loss. During the first 12 weeks of pregnancy, aPL can inhibit the growth of the early fetal cells and later cause blood clots in the blood vessels of the placenta in the second and third trimester (14-36 weeks). This means that the placenta is unable to supply the fetus with enough nutrition, so the fetus may stop growing, grow slowly (intrauterine growth restriction) and in extreme cases may die. Some mothers in this situation also develop pre-eclampsia (high blood pressure during pregnancy and after labour).
Pregnant women with aPL are treated with aspirin, and sometimes heparin, depending on whether they had blood clots and/or obstetric problems before. This has improved the live birth rate to over 70%.
A study of women with aPL who were taking hydroxychloroquine (HCQ) during pregnancy to treat lupus found that women taking HCQ had a better pregnancy outcome compared to women who do not take it, with fewer miscarriages and preterm births and a higher live birth rate. HCQ is safe in pregnancy, well-tolerated, and costs only £0.10 per tablet in the UK.
To find out more about this, in this study women with aPL are treated either with HCQ or a placebo (dummy drug) throughout pregnancy in addition to their usual medications, and pregnancy outcomes are compared.
Who can participate?
Women aged 18 to 45 with persistent antiphospholipid antibodies who are planning a pregnancy
What does the study involve?
Participants are randomly allocated to take HCQ or a placebo (dummy drug) as one tablet each day until delivery. Pregnancy outcomes are assessed.
What are the possible benefits and risks of participating?
There are no immediate benefits, but participation will help to find out if hydroxychloroquine has positive effects on pregnancy outcomes. It might therefore be beneficial for the individual for their future pregnancy.
Where is the study run from?
St Thomas' Hospital (UK)
When is the study starting and how long is it expected to run for?
January 2016 to December 2029
Who is funding the study?
1. National Institute for Health Research (NIHR) Research for Patient Benefit Programme (UK)
2. Guy's and St Thomas' Charity (UK)
Who is the main contact?
Prof. Beverley Hunt, beverley.hunt12@nhs.net
Contact information
Scientific
Thrombosis and Haemophilia
St Thomas' Hospital
Westminster Bridge Road
London
SE1 7EH
United Kingdom
| Phone | +44 (0)20 7188 2736 |
|---|---|
| beverley.hunt12@nhs.net |
Scientific
Danish Hospital for Rheuamtic diseases
Sonderburg
6400
Denmark
| Phone | +45 (0)60550372 |
|---|---|
| kschreiber@danskgigthospital.dk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Multicentre interventional randomized controlled trial |
| Secondary study design | Randomised controlled trial |
| Participant information sheet | ISRCTN19920789_PIS_V3.0.pdf |
| Scientific title | HYPATIA: A prospective randomised controlled trial of HYdroxychloroquine to improve Pregnancy outcome in women with AnTIphospholipid Antibodies |
| Study acronym | HYPATIA |
| Study objectives | Hydroxychloroquine reduces antiphospholipid antibody-mediated pregnancy morbidity. |
| Ethics approval(s) | Approved 09/03/2018, London Bridge Research Ethics Committee (London Bridge Ethics Committee, Skipton House, 80 London Road, London, SE1 6LH, UK; +44 (0)207 104 8019 or +44 (0)207 104 8124; londonbridge.rec@hra.nhs.uk), REC ref: 170254 |
| Health condition(s) or problem(s) studied | Women with persistent antiphospholipid antibodies who are planning pregnancy |
| Intervention | Method of randomisation is double-blind randomisation provided by the King's Clinical Trials Unit. Participants are randomized to take a hydroxychloroquine 200 mg tablet or a placebo once daily. The total duration of treatment is maximum 12 months before pregnancy and then the individual pregnancy length (max 9 months), maximum total of 21 months treatment. |
| Intervention type | Drug |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Hydroxychloroquine |
| Primary outcome measure(s) |
A composite of three principal aPL-related adverse pregnancy outcomes: one or more pregnancy loss(es) (either <10 weeks gestation or beyond 10 weeks of gestation of a morphologically normal fetus documented by ultrasound or by direct examination of the fetus), premature birth of a morphologically normal neonate before 34 weeks due to any of pre-eclampsia, eclampsia, recognized features of placental insufficiency. Premature birth for other reasons will not be included. |
| Key secondary outcome measure(s) |
Measured using patient/child medical records: |
| Completion date | 31/12/2029 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 45 Years |
| Sex | Female |
| Target sample size at registration | 400 |
| Key inclusion criteria | 1. Women with known aPL (i.e. isolated aPL or APS) who are planning pregnancy. aPL are defined by the presence of a positive test for anticardiolipin antibodies (IgG/IgM isotypes > 95th percentile) and/or lupus anticoagulant and/or anti- beta 2 glycoprotein-I (IgG/IgM isotypes >95th percentile), on two or more consecutive occasions more than 12 weeks apart (a positive aPL test is defined under ‘glossary and definitions’). The last positive test must be within 12 months of study entry. 2. Written informed consent to participate |
| Key exclusion criteria | 1. Women who are already pregnant 2. Allergy or adverse event to hydroxychloroquine. Hypersensitivity to the active substance, 4-aminoquinoline or any of the compounds of the IMP or placebo 3. Current treatment with hydroxychloroquine 4. Age < 18 and > 45 5. Bodyweight < 45 kg 6. Psoriasis 7. Uncontrolled epilepsy 8. Anti-Ro antibodies 9. Renal replacement therapy 10. Other severe active co-morbidities (HIV, hepatitis B, severe gastrointestinal, neurological or blood disorders) 11. Porphyria 12. History of retinopathy or newly diagnosed retinopathy 13. History of galactose intolerance, lactase deficiency or glucose-galactose malabsorption 14. History of glucose-6-dehydrogenase deficiency 15. Participation in any other IMP trial at the time of consent 16. Previous pregnancy failure on hydroxychloroquine |
| Date of first enrolment | 01/07/2017 |
| Date of final enrolment | 31/05/2028 |
Locations
Countries of recruitment
- United Kingdom
- England
- Denmark
- Italy
- Netherlands
Study participating centres
London
SE1 7EH
United Kingdom
NW1 2BU
United Kingdom
NW2 1NY
United Kingdom
OX3 9DU
United Kingdom
L8 7 SS
United Kingdom
CB2 0QQ
United Kingdom
2600
Denmark
5000
Denmark
1105
Netherlands
10124
Italy
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 01/09/2017 | 27/08/2020 | Yes | No |
| Participant information sheet | version V3.0 | 05/09/2020 | No | Yes | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | version 10.0 | 12/12/2022 | 03/11/2023 | No | No |
Additional files
- ISRCTN19920789_PIS_V3.0.pdf
- Uploaded 05/09/2020
- ISRCTN19920789_PROTOCOL_V10.0_12Dec22.pdf
- Protocol file
Editorial Notes
12/09/2025: The following changes were made to the study record:
1. The date of final enrolment was changed from 31/12/2024 to 31/05/2028.
2. The completion date was changed from 12/12/2025 to 31/12/2029.
3. Contact details updated.
03/11/2023: Protocol file uploaded.
21/06/2022: The following changes were made to the trial record:
1. The overall trial end date was changed from 31/10/2024 to 12/12/2025.
2. The intention to publish date was changed from 01/12/2024 to 01/07/2026.
20/06/2022: The recruitment end date was changed from 30/06/2022 to 31/12/2024.
17/09/2021: Internal review.
05/09/2020: The participant information sheet has been uploaded as an additional file.
27/08/2020: Trial's existence confirmed by the NIHR.
