Condition category
Pregnancy and Childbirth
Date applied
26/08/2020
Date assigned
27/08/2020
Last edited
05/09/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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 October 2024

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

Trial website

Contact information

Type

Scientific

Primary contact

Prof Beverley Hunt

ORCID ID

Contact details

Thrombosis and Haemophilia
St Thomas' Hospital
Westminster Bridge Road
London
SE1 7EH
United Kingdom
+44 (0)20 7188 2736
beverley.hunt@gstt.nhs.uk

Type

Scientific

Additional contact

Dr Karen Schreiber

ORCID ID

Contact details

Danish Hospital for Rheuamtic diseases
Sonderburg
6400
Denmark
+45 (0)60550372
karen.schreiber@gstt.nhs.uk

Additional identifiers

EudraCT number

2016-002256-25

ClinicalTrials.gov number

Nil known

Protocol/serial number

8.1, CPMS 37234

Study information

Scientific title

HYPATIA: A prospective randomised controlled trial of HYdroxychloroquine to improve Pregnancy outcome in women with AnTIphospholipid Antibodies

Acronym

HYPATIA

Study hypothesis

Hydroxychloroquine reduces antiphospholipid antibody-mediated pregnancy morbidity.

Ethics approval

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

Study design

Multicentre interventional randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

See additional file ISRCTN19920789_PIS_V3.0 (added 05/09/2020)

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

Phase

Phase III

Drug names

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 trial start date

01/01/2016

Overall trial end date

31/10/2024

Reason abandoned (if study stopped)

Eligibility

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 type

Patient

Age group

Adult

Gender

Female

Target number of participants

400

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

30/06/2022

Locations

Countries of recruitment

Denmark, Italy, Netherlands, United Kingdom

Trial participating centre

Guy's and St Thomas' NHS Foundation Trust
Westminster Bridge Road
London
SE1 7EH
United Kingdom

Trial participating centre

University College London Hostpitals
London
NW1 2BU
United Kingdom

Trial participating centre

Imperial College London
London
NW2 1NY
United Kingdom

Trial participating centre

University Hospitals Oxford
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Liverpool Women’s Hospital
Liverpool
L8 7 SS
United Kingdom

Trial participating centre

Addenbrook's University Hospital Cambridge
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Rigshospitalet Copenhagen University Hospital
Copenhagen
2600
Denmark

Trial participating centre

Odense University Hospital
Odense
5000
Denmark

Trial participating centre

Academic Medical Centre
Amsterdam
1105
Netherlands

Trial participating centre

Turin University Hospital
Turin
10124
Italy

Sponsor information

Organisation

Guy's and St Thomas' NHS Foundation Trust

Sponsor details

King’s Health Partners Clinical Trial Office
16th Floor
Tower Wing
Guy’s Hospital
Great Maze Pond
London
SE1 7EH
United Kingdom
+44 (0)20 71885732
amy.holton@kcl.ac.uk

Sponsor type

Research organisation

Website

http://www.guysandstthomas.nhs.uk/Home.aspx

Funders

Funder type

Government

Funder name

Research for Patient Benefit Programme

Alternative name(s)

NIHR Research for Patient Benefit Programme, RfPB

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Funder name

Guy's and St Thomas' Charity

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

Other non-profit organizations

Location

United Kingdom

Results and Publications

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 statement
The data-sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/12/2024

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

2017 protocol in https://pubmed.ncbi.nlm.nih.gov/28609801/ (added 27/08/2020)

Publication citations

Additional files

Editorial Notes

05/09/2020: The participant information sheet has been uploaded as an additional file. 27/08/2020: Trial's existence confirmed by the NIHR.