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 |
| EudraCT/CTIS number | 2016-002256-25 |
| Secondary identifying numbers | 8.1, CPMS 37234 |
- Submission date
- 26/08/2020
- Registration date
- 27/08/2020
- Last edited
- 03/11/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English Summary
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 2025
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.hunt@gstt.nhs.uk
Contact information
Scientific
Thrombosis and Haemophilia
St Thomas' Hospital
Westminster Bridge Road
London
SE1 7EH
United Kingdom
| Phone | +44 (0)20 7188 2736 |
|---|---|
| beverley.hunt@gstt.nhs.uk |
Scientific
Danish Hospital for Rheuamtic diseases
Sonderburg
6400
Denmark
| Phone | +45 (0)60550372 |
|---|---|
| karen.schreiber@gstt.nhs.uk |
Study information
| Study design | Multicentre interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| 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 hypothesis | 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 |
| Condition | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Hydroxychloroquine |
| Primary outcome measure | 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. |
| Secondary outcome measures | Measured using patient/child medical records: 1. Pregnancy loss < 10 weeks gestation 2. Pregnancy loss > 10th week of gestation of a morphologically normal fetus documented by ultrasound or by direct examination of the fetus 3. Premature birth of a morphologically normal neonate < 34 weeks due to any of pre-eclampsia, eclampsia, recognized features of placental insufficiency 4. Gestational age at delivery 5. Birth weight, measured at delivery 6. Delivery by Caesarean section, measured at delivery 7. Apgar score < 7 measured at 5 min from delivery 8. Neonatal morbidity (bleeding or thrombotic complications, infections, congenital abnormalities) 9. Days to hospital discharge following delivery (mother and child) 10. Thrombotic events in the mother during pregnancy and 6 weeks postpartum 11. Days of neonate in special care 12. Safety and tolerability of hydroxychloroquine in the mother and in the neonate measured until 6 weeks postpartum |
| Overall study start date | 01/01/2016 |
| Overall study end date | 12/12/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 45 Years |
| Sex | Female |
| Target number of participants | 400 |
| Participant 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 |
| Participant 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 |
| Recruitment start date | 01/07/2017 |
| Recruitment end date | 31/12/2024 |
Locations
Countries of recruitment
- Denmark
- England
- Italy
- Netherlands
- United Kingdom
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
Sponsor information
Hospital/treatment centre
King’s Health Partners Clinical Trial Office
16th Floor
Tower Wing
Guy’s Hospital
Great Maze Pond
London
SE1 7EH
United Kingdom
| Phone | +44 (0)20 71885732 |
|---|---|
| amy.holton@kcl.ac.uk | |
| Website | http://www.guysandstthomas.nhs.uk/Home.aspx |
"ROR" |
https://ror.org/00j161312 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Research for Patient Benefit Programme, RfPB
- Location
- United Kingdom
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Guy's and St Thomas' Charity, Guy's and St Thomas' Foundation, GSTTFoundation
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/07/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | On successful completion of the HYPATIA study, the results of the study will be disseminated to medical professionals and our patients. The final results will be submitted to major peer-review journals. The researchers will present these findings at national and international conferences including obstetric, rheumatologic, haematological and vascular medicine conferences. They are well served by their PIs who come from disparate clinical areas and will therefore disseminate the results to a wide audience. As clinical guidelines are based upon evidence-based medicine, this multicentre trial is likely to reach clinical specialists all over the world. Locally in the UK the researchers will update their teams about the outcome of the study and revise and update standard of care protocols. The treatment protocols are under continuous revision in order to improve the care of patients and the decisions of major changes comply with the principles of evidence-based medicine and, if not available, based on expert opinions. The researchers will also present their findings at patients’ days of Thrombosis UK & World Thrombosis Day. |
| 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 | |
| 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
Editorial Notes
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.
