Severe PreeclampsiaMAP 2NCT07665112

Algorithm-Based Timing of Delivery Using the sFlt-1/PlGF Ratio in Early-Onset Severe Preeclampsia. (MAP 2 Study : Management Based on Angiogenic Markers in Preeclampsia 2 Study )

A study testing sFlt-1/PlGF ratio-guided management algorithm in people with Severe Preeclampsia, run by Hospital Clinic of Barcelona at 1 site in Spain.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Severe Preeclampsia
What is being tested?: sFlt-1/PlGF ratio-guided management algorithm
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 386 participants
Where: 1 siteSpain
Study dates: 1 Jul 2026to 31 Dec 2029
Phase: Interventional
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Women aged 18 or older
Singleton pregnancies
Diagnosed with severe preeclampsia per 2020 ACOG criteria, between 30.0 and 33.6 weeks by first-trimester ultrasound.

Who cannot join

Major fetal malformations
Confirmed genetic syndromes.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Cesar Gil Armas, MD contact

+34 638298597

gil3@recerca.clinic.cat

Spain1 site

c/ Sabino Arana, 1. 08028 Barcelona
Barcelona, Barcelona, 08028
Cesar David Gil Armas, MD, 638298597, gil3@recerca.clinic.cat
Francesc Figueras Retuerta, PhD, +34649835994, ffiguera@clinic.cat

Other trials in Spain

About this study

Official title: Multicenter Randomized Trial of an sFlt-1/PlGF Ratio-Based Algorithm for Timing of Delivery in Early-Onset Severe Preeclampsia: The MAP 2 Study

Preeclampsia is a serious pregnancy complication caused by abnormal placental development and function. It can lead to high blood pressure and damage to organs such as the liver, kidneys, brain, or cardiovascular system. In these cases, the only definitive treatment is delivery. However, deciding when to deliver is challenging: delaying delivery increases risks for both mother and baby, while delivering too early increases complications related to prematurity.

This study aims to evaluate whether a blood test measuring the sFlt-1/PlGF ratio an angiogenic marker that reflects placental function and predicts complications more accurately than traditional clinical criteria can help determine the optimal timing of delivery in women with severe preeclampsia between 30 weeks and 33 weeks plus 6 days of gestation. It is a multicenter, randomized controlled clinical trial conducted in 11 referral hospitals in Spain and will include 386 singleton pregnancies.

Participants will be randomly assigned to one of two groups. In the control group, standard expectant management will be followed, aiming to continue the pregnancy until 34 weeks if maternal and fetal conditions remain stable, and the sFlt-1/PlGF results will be masked. In the study group, delivery timing will be guided by the sFlt-1/PlGF ratio: if the ratio is greater than 655, delivery will be planned from 30 weeks onward; if greater than 110, delivery will be planned from 34 weeks; and if 110 or lower, pregnancy may continue until 37 weeks.

The study has two primary outcomes. The first is a composite of severe maternal complications, including neurological, hepatic, renal, respiratory, or cardiovascular dysfunction, severe hypertension, placental abruption, or fetal death. The second is a composite of neonatal complications, including admission to the neonatal intensive care unit or neonatal death.

The goal is to demonstrate that using angiogenic markers reduces maternal complications without significantly increasing neonatal complications. If successful, this approach could support more individualized management of early-onset severe preeclampsia, improving maternal safety while carefully balancing the risks of prematurity for the newborn.

Read the detailed description

This is a multicenter, open-label, randomized controlled clinical trial designed to evaluate whether incorporating maternal angiogenic markers into clinical decision-making improves outcomes in early-onset severe preeclampsia. The study will include 386 singleton pregnancies diagnosed with preeclampsia with severe features according to ACOG criteria between 30+0 and 33+6 weeks of gestation across 11 tertiary referral centers in Spain. At inclusion, the maternal plasma sFlt-1/PlGF ratio will be measured in all participants. Women will then be randomly assigned (1:1) to either standard expectant management (control group) or angiogenic marker-guided management (intervention group) using a centralized REDCap randomization system that will generate the allocation sequence in blocks of 10, stratified by participating center. In the control group, clinical management will follow current standard practice, with planned delivery at 34 weeks if maternal and fetal conditions remain stable, and sFlt-1/PlGF results will be masked to treating clinicians. In the intervention group, timing of delivery will be guided by predefined sFlt-1/PlGF thresholds: >655 from 30+0 weeks, >110 from 34+0 weeks, and ≤110 allowing expectant management up to 37 weeks, provided no other obstetric indication for delivery arises. The primary objective is to evaluate whether the use of an algorithm based on the sFlt-1/PlGF ratio to guide the timing of delivery in women with early-onset severe preeclampsia with severe features improves maternal and neonatal outcomes compared with standard management. Secondary objectives include evaluating the predictive value of baseline and longitudinal sFlt-1/PlGF measurements, assessing the association between angiogenic marker abnormalities and disease progression, determining their relationship with placental dysfunction assessed by Doppler and histopathological examination, and evaluating the impact of the algorithm on maternal and neonatal healthcare resource utilization. Analyses will follow the intention-to-treat principle and will account for the multicenter design of the study.

Conditions: Severe Preeclampsia
Being tested: sFlt-1/PlGF ratio-guided management algorithm, Usual Care
Keywords: Angiogenic biomarkers, sFlt-1/PlGF ratio
Medical subject headings: Pre-Eclampsia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

sFlt-1/PlGF ratio-guided management algorithmOther
Management will be optimized based on angiogenic factor results. The sFlt-1/PlGF ratio will be determined at 30.0 weeks or at diagnosis between 30.0 and 33.6 weeks of gestation, and weekly measurements will be repeated. Based on predefined thresholds, delivery will be planned as follows: if sFlt-1/PlGF >655, planned delivery will occur after fetal lung maturation if gestational age is <35 weeks; if sFlt-1/PlGF <655 and ≥110, planned delivery will occur after 34 weeks (with prior lung maturation if gestational age is <35 weeks); and if sFlt-1/PlGF <110, planned delivery will occur at 37 weeks. If immediate delivery criteria are met, delivery will be recommended regardless of the ratio.
Usual CareOther
The control arm will receive usual care for severe preeclampsia according to each center's clinical protocols. The sFlt-1/PIGF ratio will be determined at 30 weeks or diagnosis between 30 and 33.6 weeks of gestation, and weekly measurements will be repeated, but the ratio will not be available to the clinician or researchers

Study groups in NCT07665112
Study group	Role	What they receive
sFlt-1/PlGF ratio-based management algorithm	Experimental	In the intervention arm, participants will be managed according to a predefined algorithm based on the sFlt-1/PlGF ratio, which will guide the timing of delivery according to established thresholds and gestational age. Receives: Other: sFlt-1/PlGF ratio-guided management algorithm
Standard care	Active comparator	The control arm will receive usual care for severe preeclampsia according to each center's clinical protocols. Receives: Other: Usual Care

What is being measured

The primary outcome is the main question the study is designed to answer.

Composite adverse maternal and fetal outcomes
Dichotomous outcome: occurrence of ≥1 maternal or fetal complication from randomization to delivery. Complications included: (1) central nervous system dysfunction (eclampsia, Glasgow Coma Scale <13, stroke, reversible ischaemic neurological deficit, or cortical blindness); (2) hepatic dysfunction (INR >1.2 without disseminated intravascular coagulation, MELD score >10, or hepatic hematoma/rupture); (3) renal dysfunction (dialysis, serum creatinine >1.5 mg/dL, urine output <0.5 mL/kg/h over 12 h per RIFLE criteria, or need for furosemide); (4) respiratory dysfunction (pulmonary edema, mechanical ventilation, oxygen >50% for >1 h, or severe respiratory distress with dyspnoea, crackles, and SaO₂ <90%); (5) cardiovascular dysfunction (inotropes, left ventricular failure, myocardial infarction, or transfusion >4 units); (6) resistant hypertension (≥3 drugs at maximal doses or controlled with ≥4); (7) placental abruption; and (8) stillbirth (≥22 weeks, WHO).
Measured: From randomization until delivery or completion of maternal follow-up, assessed up to 40 days postpartum.
The neonatal composite outcome
Dichotomous outcome: Occurrence of ≥1 neonatal complication, defined as neonatal death before 28 days of life or admission to a neonatal intensive care unit or high-dependency unit according to British Association of Perinatal Medicine criteria, between birth and 28 days of life.
Measured: From delivery up to neonatal discharge from hospital or neonatal death or 28 days of life (whichever comes first).

Secondary outcomes (14)

Maternal risk prediction using the fullPIERS model
The fullPIERS model is a validated prediction scoring for preeclampsia that incorporates gestational age (weeks), chest pain or dyspnea, oxygen saturation (%), platelet count (×10⁹/L), serum creatinine (mg/dL or µmol/L), and aspartate transaminase (AST, U/L) to estimate the risk of severe maternal complications, primarily within 48 hours after assessment.
Measured: From randomization until delivery, assessed up to 37 completed weeks of gestation
Maternal length of hospitalization
Duration of maternal hospitalization, defined as the number of days from randomization to hospital discharge. This is a continuous variable.
Measured: From randomization until maternal hospital discharge, assessed up to 40 days postpartum.
Intrauterine growth restriction
Occurrence of prenatal fetal growth restriction (FGR), defined as an antenatal estimated fetal weight <10th percentile for gestational age on ultrasound, assessed as a dichotomous outcome (yes/no)
Measured: From date of randomization until the last scan before delivery or fetal death, assessed up to 37 completed weeks of gestation.
Postnatal small for gestational age
Occurrence of small for gestational age (SGA), defined as birthweight <10th percentile for gestational age and sex, analyzed as a binary outcome
Measured: At delivery
Gestational age at delivery
Gestational age at delivery (in weeks):
Measured: At the time of delivery
Proportion of participants undergoing cesarean delivery
Cesarean delivery will be defined as any surgical delivery of the fetus. The outcome will be analyzed as a dichotomous variable and reported as the proportion of participants undergoing cesarean delivery .
Measured: At delivery
Neonatal morbidity according to the Morbidity Assessment Index for Newborns (MAIN)
Neonatal morbidity will be assessed using the Morbidity Assessment Index for Newborns (MAIN), a validated composite score based on 47 weighted clinical and laboratory indicators. Scores range from 0 (no morbidity) upward, with higher scores indicating greater neonatal morbidity and worse neonatal health status. Scores of 0-150 represented minimal/no morbidity, 151-500 mild morbidity, 501-800 moderate morbidity, and >800 severe morbidity .
Measured: From delivery up to neonatal discharge from hospital or neonatal death or 28 days of life (whichever comes first).
Neonatal complications
Neonatal complications will include metabolic acidosis (umbilical artery pH <7.00 and base excess <-16), Apgar score <7 at 5 minutes, bronchopulmonary dysplasia, necrotizing enterocolitis stage 2 or 3 according to Bell's classification, Grade III intraventricular haemorrhage (IVH) and periventricular haemorrhagic infarction (PHI), according to the contemporary classification proposed by Parodi (28), periventricular leukomalacia, retinopathy stage 3-5, hypoxic-ischemic encephalopathy (defined by Apgar score <5 at 10 minutes, umbilical artery pH <7.00, or base excess >-16 at 60 minutes, associated with neurological signs), neonatal renal insufficiency (creatinine >1.5 mg/dL), and the need for inotropic agents.
Measured: From delivery up to neonatal discharge from hospital or neonatal death or 28 days of life (whichever comes first).
Days of admission in the neonatal high-dependency care unit
Number of days admitted in the high-dependency care unit
Measured: From delivery up to neonatal discharge from hospital or neonatal death or 28 days of life (whichever comes first)
Days of neonatal admission to the intensive care unit
Lenght of neonatal stay from admission to discharge from NICU
Measured: From delivery up to neonatal discharge from hospital or neonatal death or 28 days of life (whichever comes first).
Uterine artery pulsatility index
Mean uterine artery pulsatility index measured by Doppler ultrasound.
Measured: From date of randomization until the last scan before delivery or fetal death, assessed up to 37 completed weeks of gestation.
Middle cerebral artery pulsatility index
Middle cerebral artery pulsatility index measured by fetal Doppler ultrasound.
Measured: From date of randomization until the last scan before delivery or fetal death, assessed up to 37 completed weeks of gestation.
Umbilical artery pulsatility index
Umbilical artery pulsatility index measured by Doppler ultrasound.
Measured: From date of randomization until the last scan before delivery or fetal death, assessed up to 37 completed weeks of gestation.
Placental dysfunction (histological assessment)
Placental dysfunction assessed by histopathological examination according to the Amsterdam consensus classification, including features of maternal vascular malperfusion and fetal vascular malperfusion
Measured: At delivery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jul 202631 Dec 2029

First posted24 Jun 2026
Study start1 Jul 2026 (estimated)
Primary completion30 Sep 2029 (estimated)
Study completion31 Dec 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (23)Papers the sponsor has linked to this study.
Other trials for Severe PreeclampsiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Multicenter, randomized, open-label, controlled trial of superiority conducted across 11 national reference university hospitals in Spain, with two parallel groups . Participants will be recruited at diagnosis or at 30 weeks' gestation if preeclampsia was previously identified. Participants will be randomized to one of the two study arms in a 1:1 ratio to the intervention group or the control group using the online service (REDCap) that will generate the randomized sequence in blocks of 10 stratified by participating center. The allocation will be sequestered internally by a Clinical Trials Unit. The management of patients will follow the standard practices of the participating center and include the administration of corticosteroids for fetal lung maturation, magnesium sulfate for eclampsia prophylaxis, and clinical laboratory monitoring according to established protocols.
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 386 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07665112
Sponsor's protocol ID: PI25/00371
Other IDs: PI25/00371
Acronym: MAP 2
Status last verified: Jun 2026
First submitted: 13 Mar 2026
Last updated: 24 Jun 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: De-identified individual participant data underlying the results reported in publications arising from this study will be made available, including baseline maternal characteristics, angiogenic marker measurements, treatment allocation, delivery timing, and maternal and neonatal outcomes. The study protocol, statistical analysis plan, and data dictionary may also be made available. Data will be shared after publication of the primary results, upon reasonable request, with qualified researchers who provide a methodologically sound proposal and obtain any required ethics approvals. Data access will be granted after review and approval by the study investigators and the sponsoring institution, and after signature of a data access agreement.

Publications

Peguero A, Fernandez-Blanco L, Mazarico E, Benitez L, Gonzalez A, Youssef L, Crispi F, Hernandez S, Figueras F. Added prognostic value of longitudinal changes of angiogenic factors in early-onset severe pre-eclampsia: a prospective cohort study. BJOG. 2021 Jan;128(2):158-165. doi: 10.1111/1471-0528.16383. Epub 2020 Jul 21.
PubMed 32593222
Peguero A, Herraiz I, Perales A, Melchor JC, Melchor I, Marcos B, Villalain C, Martinez-Portilla R, Mazarico E, Meler E, Hernandez S, Matas I, Del Rio M, Galindo A, Figueras F. Placental growth factor testing in the management of late preterm preeclampsia without severe features: a multicenter, randomized, controlled trial. Am J Obstet Gynecol. 2021 Sep;225(3):308.e1-308.e14. doi: 10.1016/j.ajog.2021.03.044. Epub 2021 Apr 3.
PubMed 33823150
Iams JD, Romero R, Culhane JF, Goldenberg RL. Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth. Lancet. 2008 Jan 12;371(9607):164-75. doi: 10.1016/S0140-6736(08)60108-7.
PubMed 18191687
Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol. 2013 Dec;209(6):544.e1-544.e12. doi: 10.1016/j.ajog.2013.08.019. Epub 2013 Aug 22.
PubMed 23973398
Rana S, Powe CE, Salahuddin S, Verlohren S, Perschel FH, Levine RJ, Lim KH, Wenger JB, Thadhani R, Karumanchi SA. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation. 2012 Feb 21;125(7):911-9. doi: 10.1161/CIRCULATIONAHA.111.054361. Epub 2012 Jan 18.
PubMed 22261192
Soundararajan R, Suresh SC, Mueller A, Heimberger S, Avula S, Sathyanarayana C, Mahesh S, Madhuprakash S, Rana S. Real life outpatient biomarker use in management of hypertensive pregnancies in third trimester in a low resource SeTting: ROBUST study. Pregnancy Hypertens. 2021 Mar;23:97-103. doi: 10.1016/j.preghy.2020.11.010. Epub 2020 Dec 3.
PubMed 33307400
Lopes Perdigao J, Chinthala S, Mueller A, Minhas R, Ramadan H, Nasim R, Naseem H, Young D, Shahul S, Chan SL, Yeo KJ, Rana S. Angiogenic Factor Estimation as a Warning Sign of Preeclampsia-Related Peripartum Morbidity Among Hospitalized Patients. Hypertension. 2019 Apr;73(4):868-877. doi: 10.1161/HYPERTENSIONAHA.118.12205.
PubMed 30798660
Sibiude J, Guibourdenche J, Dionne MD, Le Ray C, Anselem O, Serreau R, Goffinet F, Tsatsaris V. Placental growth factor for the prediction of adverse outcomes in patients with suspected preeclampsia or intrauterine growth restriction. PLoS One. 2012;7(11):e50208. doi: 10.1371/journal.pone.0050208. Epub 2012 Nov 28.
PubMed 23209675
Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, Calda P, Holzgreve W, Galindo A, Engels T, Denk B, Stepan H. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol. 2012 Jan;206(1):58.e1-8. doi: 10.1016/j.ajog.2011.07.037. Epub 2011 Jul 30.
PubMed 22000672
Verlohren S, Galindo A, Schlembach D, Zeisler H, Herraiz I, Moertl MG, Pape J, Dudenhausen JW, Denk B, Stepan H. An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia. Am J Obstet Gynecol. 2010 Feb;202(2):161.e1-161.e11. doi: 10.1016/j.ajog.2009.09.016. Epub 2009 Oct 21.
PubMed 19850276
Chappell LC, Duckworth S, Seed PT, Griffin M, Myers J, Mackillop L, Simpson N, Waugh J, Anumba D, Kenny LC, Redman CW, Shennan AH. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation. 2013 Nov 5;128(19):2121-31. doi: 10.1161/CIRCULATIONAHA.113.003215.
PubMed 24190934
Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennstrom M, Olovsson M, Brennecke SP, Stepan H, Allegranza D, Dilba P, Schoedl M, Hund M, Verlohren S. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med. 2016 Jan 7;374(1):13-22. doi: 10.1056/NEJMoa1414838.
PubMed 26735990
Zhang J, Klebanoff MA, Roberts JM. Prediction of adverse outcomes by common definitions of hypertension in pregnancy. Obstet Gynecol. 2001 Feb;97(2):261-7. doi: 10.1016/s0029-7844(00)01125-x.
PubMed 11165592
Romero R, Nien JK, Espinoza J, Todem D, Fu W, Chung H, Kusanovic JP, Gotsch F, Erez O, Mazaki-Tovi S, Gomez R, Edwin S, Chaiworapongsa T, Levine RJ, Karumanchi SA. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med. 2008 Jan;21(1):9-23. doi: 10.1080/14767050701830480.
PubMed 18175241
Wang A, Rana S, Karumanchi SA. Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology (Bethesda). 2009 Jun;24:147-58. doi: 10.1152/physiol.00043.2008.
PubMed 19509125

Interested in taking part?

Cesar Gil Armas, MD

+34 638298597

gil3@recerca.clinic.cat

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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All Severe Preeclampsia trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Multicenter Randomized Trial of an sFlt-1/PlGF Ratio-Based Algorithm for Timing of Delivery in Early-Onset Severe Preeclampsia: The MAP 2 Study
ClinicalTrials.gov ID: NCT07665112
Acronym / sponsor ID: MAP 2 / PI25/00371
Conditions: Severe Preeclampsia
Keywords: Angiogenic biomarkers, sFlt-1/PlGF ratio
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 386 participants (estimated)
Lead sponsor: Hospital Clinic of BarcelonaUniversity, hospital or other
Collaborators: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain., Hospital Universitario 12 de Octubre, Hospital de Sant Pau, Fundació Sant Joan de Déu, Hospital Universitario La Paz, Hospital Materno-Infantil de Canarias. Las Palmas de Gran Canaria. Spain, Hospital Son Llatzer, Hospital Clinico Universitario San Cecilio, Hospital Universitario Virgen de la Arrixaca, Fundacion Para La Investigacion Hospital La Fe, Hospital Vall d'Hebron
Study start: 1 Jul 2026 (estimated)
Primary completion: 30 Sep 2029 (estimated)
Study completion: 31 Dec 2029 (estimated)
First posted: 24 Jun 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2
Model description: Multicenter, randomized, open-label, controlled trial of superiority conducted across 11 national reference university hospitals in Spain, with two parallel groups . Participants will be recruited at diagnosis or at 30 weeks' gestation if preeclampsia was previously identified. Participants will be randomized to one of the two study arms in a 1:1 ratio to the intervention group or the control group using the online service (REDCap) that will generate the randomized sequence in blocks of 10 stratified by participating center. The allocation will be sequestered internally by a Clinical Trials Unit. The management of patients will follow the standard practices of the participating center and include the administration of corticosteroids for fetal lung maturation, magnesium sulfate for eclampsia prophylaxis, and clinical laboratory monitoring according to established protocols.

Arm	Type	Receives
sFlt-1/PlGF ratio-based management algorithm	Experimental	Other: sFlt-1/PlGF ratio-guided management algorithmIn the intervention arm, participants will be managed according to a predefined algorithm based on the sFlt-1/PlGF ratio, which will guide the timing of delivery according to established thresholds and gestational age.
Standard care	Active comparator	Other: Usual CareThe control arm will receive usual care for severe preeclampsia according to each center's clinical protocols.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Women aged 18 or older
Singleton pregnancies
Diagnosed with severe preeclampsia per 2020 ACOG criteria, between 30.0 and 33.6 weeks by first-trimester ultrasound.

Key exclusion criteria (2 listed)

Major fetal malformations
Confirmed genetic syndromes.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
sFlt-1/PlGF ratio-guided management algorithmManagement will be optimized based on angiogenic factor results. The sFlt-1/PlGF ratio will be determined at 30.0 weeks or at diagnosis between 30.0 and 33.6 weeks of gestation, and weekly measurements will be repeated. Based on predefined thresholds, delivery will be planned as follows: if sFlt-1/PlGF >655, planned delivery will occur after fetal lung maturation if gestational age is <35 weeks; if sFlt-1/PlGF <655 and ≥110, planned delivery will occur after 34 weeks (with prior lung maturation if gestational age is <35 weeks); and if sFlt-1/PlGF <110, planned delivery will occur at 37 weeks. If immediate delivery criteria are met, delivery will be recommended regardless of the ratio.	Other	sFlt-1/PlGF ratio-based management algorithm
Usual CareThe control arm will receive usual care for severe preeclampsia according to each center's clinical protocols. The sFlt-1/PIGF ratio will be determined at 30 weeks or diagnosis between 30 and 33.6 weeks of gestation, and weekly measurements will be repeated, but the ratio will not be available to the clinician or researchers	Other	Standard care

Primary outcome

Composite adverse maternal and fetal outcomes
Time frame: From randomization until delivery or completion of maternal follow-up, assessed up to 40 days postpartum.
Dichotomous outcome: occurrence of ≥1 maternal or fetal complication from randomization to delivery. Complications included: (1) central nervous system dysfunction (eclampsia, Glasgow Coma Scale <13, stroke, reversible ischaemic neurological deficit, or cortical blindness); (2) hepatic dysfunction (INR >1.2 without disseminated intravascular coagulation, MELD score >10, or hepatic hematoma/rupture); (3) renal dysfunction (dialysis, serum creatinine >1.5 mg/dL, urine output <0.5 mL/kg/h over 12 h per RIFLE criteria, or need for furosemide); (4) respiratory dysfunction (pulmonary edema, mechanical ventilation, oxygen >50% for >1 h, or severe respiratory distress with dyspnoea, crackles, and SaO₂ <90%); (5) cardiovascular dysfunction (inotropes, left ventricular failure, myocardial infarction, or transfusion >4 units); (6) resistant hypertension (≥3 drugs at maximal doses or controlled with ≥4); (7) placental abruption; and (8) stillbirth (≥22 weeks, WHO).
The neonatal composite outcome
Time frame: From delivery up to neonatal discharge from hospital or neonatal death or 28 days of life (whichever comes first).
Dichotomous outcome: Occurrence of ≥1 neonatal complication, defined as neonatal death before 28 days of life or admission to a neonatal intensive care unit or high-dependency unit according to British Association of Perinatal Medicine criteria, between birth and 28 days of life.

14 secondary outcomes

Maternal risk prediction using the fullPIERS model
Time frame: From randomization until delivery, assessed up to 37 completed weeks of gestation
Maternal length of hospitalization
Time frame: From randomization until maternal hospital discharge, assessed up to 40 days postpartum.
Intrauterine growth restriction
Time frame: From date of randomization until the last scan before delivery or fetal death, assessed up to 37 completed weeks of gestation.
Postnatal small for gestational age
Time frame: At delivery
Gestational age at delivery
Time frame: At the time of delivery
Proportion of participants undergoing cesarean delivery
Time frame: At delivery
Neonatal morbidity according to the Morbidity Assessment Index for Newborns (MAIN)
Time frame: From delivery up to neonatal discharge from hospital or neonatal death or 28 days of life (whichever comes first).
Neonatal complications
Time frame: From delivery up to neonatal discharge from hospital or neonatal death or 28 days of life (whichever comes first).
Days of admission in the neonatal high-dependency care unit
Time frame: From delivery up to neonatal discharge from hospital or neonatal death or 28 days of life (whichever comes first)
Days of neonatal admission to the intensive care unit
Time frame: From delivery up to neonatal discharge from hospital or neonatal death or 28 days of life (whichever comes first).
Uterine artery pulsatility index
Time frame: From date of randomization until the last scan before delivery or fetal death, assessed up to 37 completed weeks of gestation.
Middle cerebral artery pulsatility index
Time frame: From date of randomization until the last scan before delivery or fetal death, assessed up to 37 completed weeks of gestation.
Umbilical artery pulsatility index
Time frame: From date of randomization until the last scan before delivery or fetal death, assessed up to 37 completed weeks of gestation.
Placental dysfunction (histological assessment)
Time frame: At delivery

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2026.
Background: PubMed 32593222Peguero A, Fernandez-Blanco L, Mazarico E, Benitez L, Gonzalez A, Youssef L, Crispi F, Hernandez S, Figueras F. Added prognostic value of longitudinal changes of angiogenic factors in early-onset severe pre-eclampsia: a prospective cohort study. BJOG. 2021 Jan;128(2):158-165. doi: 10.1111/1471-0528.16383. Epub 2020 Jul 21.
Background: PubMed 33823150Peguero A, Herraiz I, Perales A, Melchor JC, Melchor I, Marcos B, Villalain C, Martinez-Portilla R, Mazarico E, Meler E, Hernandez S, Matas I, Del Rio M, Galindo A, Figueras F. Placental growth factor testing in the management of late preterm preeclampsia without severe features: a multicenter, randomized, controlled trial. Am J Obstet Gynecol. 2021 Sep;225(3):308.e1-308.e14. doi: 10.1016/j.ajog.2021.03.044. Epub 2021 Apr 3.
Background: PubMed 18191687Iams JD, Romero R, Culhane JF, Goldenberg RL. Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth. Lancet. 2008 Jan 12;371(9607):164-75. doi: 10.1016/S0140-6736(08)60108-7.
Background: PubMed 23973398Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol. 2013 Dec;209(6):544.e1-544.e12. doi: 10.1016/j.ajog.2013.08.019. Epub 2013 Aug 22.
Background: PubMed 22261192Rana S, Powe CE, Salahuddin S, Verlohren S, Perschel FH, Levine RJ, Lim KH, Wenger JB, Thadhani R, Karumanchi SA. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation. 2012 Feb 21;125(7):911-9. doi: 10.1161/CIRCULATIONAHA.111.054361. Epub 2012 Jan 18.
Background: PubMed 33307400Soundararajan R, Suresh SC, Mueller A, Heimberger S, Avula S, Sathyanarayana C, Mahesh S, Madhuprakash S, Rana S. Real life outpatient biomarker use in management of hypertensive pregnancies in third trimester in a low resource SeTting: ROBUST study. Pregnancy Hypertens. 2021 Mar;23:97-103. doi: 10.1016/j.preghy.2020.11.010. Epub 2020 Dec 3.
Background: PubMed 30798660Lopes Perdigao J, Chinthala S, Mueller A, Minhas R, Ramadan H, Nasim R, Naseem H, Young D, Shahul S, Chan SL, Yeo KJ, Rana S. Angiogenic Factor Estimation as a Warning Sign of Preeclampsia-Related Peripartum Morbidity Among Hospitalized Patients. Hypertension. 2019 Apr;73(4):868-877. doi: 10.1161/HYPERTENSIONAHA.118.12205.
Background: PubMed 23209675Sibiude J, Guibourdenche J, Dionne MD, Le Ray C, Anselem O, Serreau R, Goffinet F, Tsatsaris V. Placental growth factor for the prediction of adverse outcomes in patients with suspected preeclampsia or intrauterine growth restriction. PLoS One. 2012;7(11):e50208. doi: 10.1371/journal.pone.0050208. Epub 2012 Nov 28.
Background: PubMed 22000672Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, Calda P, Holzgreve W, Galindo A, Engels T, Denk B, Stepan H. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol. 2012 Jan;206(1):58.e1-8. doi: 10.1016/j.ajog.2011.07.037. Epub 2011 Jul 30.
Background: PubMed 19850276Verlohren S, Galindo A, Schlembach D, Zeisler H, Herraiz I, Moertl MG, Pape J, Dudenhausen JW, Denk B, Stepan H. An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia. Am J Obstet Gynecol. 2010 Feb;202(2):161.e1-161.e11. doi: 10.1016/j.ajog.2009.09.016. Epub 2009 Oct 21.
Background: PubMed 24190934Chappell LC, Duckworth S, Seed PT, Griffin M, Myers J, Mackillop L, Simpson N, Waugh J, Anumba D, Kenny LC, Redman CW, Shennan AH. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation. 2013 Nov 5;128(19):2121-31. doi: 10.1161/CIRCULATIONAHA.113.003215.
Background: PubMed 26735990Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennstrom M, Olovsson M, Brennecke SP, Stepan H, Allegranza D, Dilba P, Schoedl M, Hund M, Verlohren S. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med. 2016 Jan 7;374(1):13-22. doi: 10.1056/NEJMoa1414838.
Individual participant dataSharing planned: Yes. De-identified individual participant data underlying the results reported in publications arising from this study will be made available, including baseline maternal characteristics, angiogenic marker measurements, treatment allocation, delivery timing, and maternal and neonatal outcomes. The study protocol, statistical analysis plan, and data dictionary may also be made available. Data will be shared after publication of the primary results, upon reasonable request, with qualified researchers who provide a methodologically sound proposal and obtain any required ethics approvals. Data access will be granted after review and approval by the study investigators and the sponsoring institution, and after signature of a data access agreement.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Cesar Gil Armas, MD contact

+34 638298597

gil3@recerca.clinic.cat

Francesc Figueras Retuerta, PhD principal investigator

Hospital Clinic of Barcelona

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing sFlt-1/PlGF ratio-guided management algorithm in people with Severe Preeclampsia, run by Hospital Clinic of Barcelona at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Cesar Gil Armas, MD (+34 638298597, gil3@recerca.clinic.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite adverse maternal and fetal outcomes (time frame: From randomization until delivery or completion of maternal follow-up, assessed up to 40 days postpartum.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07665112, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2026; AzTrials last refreshed its copy on 27 Oct 2026.