Does placental growth factor testing improve outcomes for women with suspected preterm pre-eclampsia in low- and middle-income countries?
| ISRCTN | ISRCTN70040289 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN70040289 |
- Submission date
- 27/04/2025
- Registration date
- 01/05/2025
- Last edited
- 01/05/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims
Preeclampsia is a serious pregnancy complication that can cause high blood pressure and organ damage in the mother, and poor growth or death of the baby. Globally, preeclampsia is one of the leading causes of death for pregnant women and their babies, especially in low- and middle-income countries (LMICs) such as those in Sub-Saharan Africa and South Asia. Each year, around 30,000 women and 500,000 babies die due to this condition—most of these deaths could be prevented with earlier diagnosis and timely delivery. Diagnosing preeclampsia in LMICs can be challenging due to limited access to tests like blood pressure monitoring, urine testing, and scans. This can lead to missed or late diagnoses with serious consequences. Placental growth factor (PlGF) is a substance in the blood that is low in women with preeclampsia. Testing for PlGF has been shown to help diagnose the condition earlier and reduce complications in high-income countries like the UK, where it is now used routinely. PlGF testing may be especially useful in low-resource settings where the need is greatest, however, its benefits have not yet been fully studied in this setting. Point-of-care PlGF tests are now available that can be done with minimal equipment or training. This study aims to test whether using point-of-care PlGF testing in LMICs improves outcomes for mothers and babies. It will also examine whether PlGF testing is cost-effective and how it affects the use of health resources.
Who can participate?
Women with suspected preeclampsia between 20 and 37 weeks of gestation, with a live, singleton pregnancy, will be able to take part in the study.
What does the study involve?
Half of the women will receive a PlGF test and care based on the results; the other half will receive the usual care available in their hospital, without a test. The outcomes of the mothers and babies will be followed until they are discharged from the hospital.
What are the possible risks and benefits of participating?
By taking part in the study, those who are allocated to receive a PlGF test will have additional information available to their medical team that may help inform their diagnosis. There may be slight discomfort associated with taking the blood test, however, no risks are expected from participation.
Where is the study run from?
The study is being run by King's College London. It will take place in sites in Brazil, India, Sierra Leone and Zambia.
When is the study starting and how long is it expected to run for?
July 2024 to June 2027. Recruitment for the study will start in May 2025 and will continue for one year, the data analysis and report writing is expected to take another year.
Who is funding the study?
The National Institute for Health and Care Research (NIHR), UK
Who is the main contact?
The trial coordinator is Louisa Samuels, louisa.samuels@kcl.ac.uk
Contact information
Principal Investigator
Department of Women and Children's Health, King's College London, 10th Floor, North Wing, St Thomas' Hospital, Westminster Bridge Road
London
SE1 7EH
United Kingdom
 ORCID ID |
0000-0001-5273-3132 |
|---|---|
| Phone | +44 (0)20 7188 7188 |
| andrew.shennan@kcl.ac.uk |
Public, Scientific
Department of Women and Children's Health, King's College London, 10th Floor, North Wing, St Thomas' Hospital, Westminster Bridge Road
London
SE1 7EH
United Kingdom
| ORCID ID |
0000-0001-5384-0458 |
|---|---|
| Phone | +44 (0)20 7188 7188 |
| louisa.samuels@kcl.ac.uk |
Study information
| Study design | Multicenter interventional open-label individual randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital, Laboratory, Medical and other records |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Placental Growth fActor testing for diagnosis of preterm preeclampsia and reductIon of adverse Outcomes in low- and middle-income countries: a pragmatic, international, open-label, randomised controlled trial |
| Study acronym | PAPAGAIO Diagnosis |
| Study objectives | The use of placental growth factor testing for diagnosis of pre-term preeclampsia, implemented alongside a clinical management algorithm, improves maternal and neonatal outcomes in low-and middle-income countries. |
| Ethics approval(s) |
1. Approved 05/03/2025, King's College London Research Ethics Committee (5-11 Lavington Street, London, SE1 0NZ, United Kingdom; +44 (0) 20 7836 5454; rec@kcl.ac.uk), ref: HR/DP-24/25-46560 2. Approved 03/02/2025, University of Zambia Biomedical Research Ethics Committee (Ridgeway Campus, Lusaka, P.O. Box 50110, Zambia; +260 977925304; unzarec@unza.zm), ref: 6222-2024 3. Approved 24/02/2025, Sierra Leone Ethics and Scientific Review Committee (Directorate of Training and Research, Youyi Building, Brookfields, Freetown, FQG2+CP5, Sierra Leone; +23278366493; efoday@mohs.gov.sl), ref: 004/02/2025 4. Approved 20/01/2025, Institutional Ethics Committee of KLE Academy of Higher Education and Research (KLES Dr Prabhakar Kore Hospital, Nehru Nagar, Belagavi, 590010, India; +91-831-255 1876; kleclinicalresearch@gmail.com), ref: KAHER/EC/2025-26/D-21012501 |
| Health condition(s) or problem(s) studied | Diagnosis of pre-term preeclampsia |
| Intervention | Participants with suspected preeclampsia will be randomised to receive either a placental growth factor test, implemented alongside a clinical management algorithm (intervention), or usual care (control). The allocation ratio will be 1:1. Randomisation will be managed by a secure web-based randomisation facility hosted by OMDA. A minimisation algorithm will ensure balance between the intervention and control group, with respect to the country, site, gestational age at randomisation (20+0 to 27+6, 28+0 to 31+6, 32+0 to 33+6, 34+0 to 36+6 weeks’ gestation), primary indication for testing (hypertension, other) and severity of hypertension (≥160mmHg, <160mmHg). Following randomisation, the participant will either receive a PlGF test, or ongoing usual care as the randomisation indicates. In the intervention (PlGF test) group, a point-of-care PlGF test will be performed on whole blood collected as soon as feasible after randomisation. The clinical teams caring for the participant will be informed of the PlGF test result. All clinicians at the trial sites will be trained in interpretation of PlGF results. A 'normal' test result will indicate that preeclampsia can be ruled out, an 'abnormal' test will indicate that preeclampsia cannot be ruled out and ongoing follow-up is required, a 'very abnormal' test will indicate a confirmed diagnosis of preeclampsia (in accordance with the International Society for the Study of Hypertension in Pregnancy guidelines). Participants will be treated in accordance with local guidelines and at the discretion of the treating clinician. The control group will receive routine clinical management according to local guidelines and clinician discretion. Participants will be followed up until postnatal discharge of both mother and baby. |
| Intervention type | Other |
| Primary outcome measure | The following primary outcome measures will be assessed from data collected from medical records at discharge, using data collected between recruitment and primary hospital discharge: 1. Primary maternal outcome: A composite of maternal mortality and morbidity (based on the miniPIERS composite of adverse maternal outcomes) during pregnancy and delivery until primary hospital discharge 2. Primary perinatal outcome: Composite of stillbirth and early neonatal death (<7 days) until primary hospital discharge |
| Secondary outcome measures | The following secondary outcome measures will be assessed from data collected from medical records at discharge, using data collected between recruitment and primary hospital discharge: Tested Maternal Outcomes: 1. Maternal mortality according to clinical diagnosis 2. Eclampsia according to clinical diagnosis 3. Placental abruption according to clinical diagnosis 4. Termination pre-viability for maternal preeclampsia according to clinical diagnosis 5. Time to diagnosis of pre-eclampsia according to the International Society for the Study of Hypertension in Pregnancy definition 6. Proportion of women diagnosed with preeclampsia according to the International Society for the Study of Hypertension (ISSHP) in pregnancy definition 7. Time to delivery 8. Mode of birth (vaginal, assisted vaginal, caesarean section) Descriptive Maternal Outcomes: 1. Stroke 2. Cortical blindness 3. Retinal detachment 4. Pulmonary oedema 5. Acute Kidney Injury and using laboratory creatinine measurements, definition according to the KIDIGO definitions 6. Liver capsule haematoma/rupture 7. Major post-partum haemorrhage 8. Hepatic dysfunction measured according to the hospital medical records and using laboratory AST/ALT measurements, definition according to ISSHP definitions 9. Low platelets measured according to the hospital medical records and using laboratory platelet measurements, definition according to ISSHP definitions 10. ICU admission 11. Intubation and ventilation (other than for delivery) 12. Glasgow coma score <13 13. Transient ischaemic attack 14. Posterior reversible encephalopathy 15. Positive inotropic support 16. Myocardial infarction/ischaemia 17. Blood oxygen saturation <90% 18. Requirement of ≥50% FiO2 for over one hour 19. Supplemental oxygen >50% for more than one hour 20. Dialysis required 21. HDU admission 22. Labour onset (spontaneous, induced or pre-labour caesarean section) 23. Indication for delivery 24. Use of MgSO4 25. Use of steroids 26. Use of antihypertensives 27. Parenteral infusion of third-line antihypertensives required Perinatal Outcomes Tested Perinatal Outcomes 1. Stillbirth 2. Early neonatal death (within 7 days of life) 3. Neonatal unit admission 4. Neonatal unit admission for more than 48 hours 5. Gestational age at delivery 6. Preterm birth before 37 weeks’ gestation 7. Preterm birth before 34 weeks’ gestation 8. Birthweight <10th centile (Intergrowth-21) Descriptive Perinatal Outcomes 1. Late neonatal death (after 7 days of life, up to primary hospital discharge) 2. Respiratory support 3. Sepsis 4. Neonatal seizures 5. Birthweight 6. Birthweight <3rd centile (Intergrowth-21) 7. Antibiotics given 8. APGARs at 1 and 5 minutes 9. Hypoxic Ischaemic Encephalopathy and grade 10. Respiratory distress syndrome 11. Supplementary oxygen and duration 12. Administration of surfactant 13. Hypoglycaemia requiring intervention 14. Hypothermia (temperature < 35.6 °c) 15. Neonatal jaundice requiring phototherapy 16. Necrotising enterocolitis 17. Nasogastric feeding required 18. Umbilical artery and venous pH 19. Abnormal cerebral ultrasound 20. Fetal sex Adherence Measures Among the intervention group: 1. Valid PlGF test result obtained, measured using a point-of-care PlGF test 2. PlGF test result documented in patient notes Among the control group: 3. PlGF test performed at any point Health resource use outcomes for budget impact analysis: 1. Number of test cartridges used measured by the research team audit 2. Number of test cartridges wasted measured by the research team audit 3. Number of failed tests measured by the research team audit Maternal: 1. Antenatal outpatient attendances 2. Formal ultrasound scans 3. Inpatient days 4. Intensive care unit days Perinatal: 1. Total days in hospital 2. Total days in each level of care (intensive care, high dependency and special care unit days) |
| Overall study start date | 01/07/2024 |
| Completion date | 30/06/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Sex | Female |
| Target number of participants | 1310 |
| Key inclusion criteria | 1. Hypertension or other clinical suspicion of preeclampsia [such as proteinuria, abnormal blood test results suggestive of preeclampsia, small for gestational age with suspicion of preeclampsia, symptoms of preeclampsia (including headache, visual disturbances, right upper quadrant pain)] 2. Between 20- and 36+6-weeks’ gestation 3. Singleton pregnancy 4. Live pregnancy 5. Able to give informed written or thumbprint consent (or assent if aged less than 18 years with parental or guardian consent) |
| Key exclusion criteria | 1. In active labour (cervix dilated more than 4cm) |
| Date of first enrolment | 26/05/2025 |
| Date of final enrolment | 29/05/2026 |
Locations
Countries of recruitment
- Brazil
- India
- Sierra Leone
- Zambia
Study participating centres
Lusaka
50001
Zambia
Ndola
10101
Zambia
Kitwe
6625+VHM
Zambia
HC8H+5QP
Zambia
Freetown
FQRJ+2CP
Sierra Leone
Jaipur
302001
India
Bhubaneswar
751025
India
Vijayapura
586103
India
Hubballi
580022
India
Belgavi
590010
India
Brasília
70840-901
Brazil
Campinas
13083-888
Brazil
Belo Horizonte
30130-100
Brazil
Botucatu
18618-970
Brazil
Ribeirão Preto
14015-010
Brazil
Recife
50670-901
Brazil
Sponsor information
University/education
Strand
London
WC2R 2LS
England
United Kingdom
| Phone | +44 (0)20 7836 5454 |
|---|---|
| bashir.al-hashimi@kcl.ac.uk | |
| Website | https://www.kcl.ac.uk/ |
"ROR" |
https://ror.org/0220mzb33 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 25/05/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from Louisa Samuels louisa.samuels@kcl.ac.uk. Type of data that will be shared: quantitative. When the data will become available and for how long: 25/05/2027 By what access criteria data will be shared including with whom: to be determined at a later date. For what types of analyses, and by what mechanism: to be determined at a later date. Whether consent from participants was obtained: Consent will be gained for the research team to use participants data for future research if ethical approval from a research committee is gained. Comments on data anonymisation: Data would only be supplied in fully anonymised format. |
Editorial Notes
28/04/2025: Study's existence confirmed by the King's College London Research Ethics Committee.
