sFlt1/PlGF and Selective Labor Induction to Prevent Preeclampsia at Term (PE37)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04766866 |
|
Recruitment Status :
Recruiting
First Posted : February 23, 2021
Last Update Posted : December 14, 2021
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
- Preeclampsia (PE) affects ~5% of pregnancies. Although improved obstetrical care has significantly diminished associated maternal mortality, PE remains a leading cause of maternal morbidity and mortality in the world.
- Term PE accounts for 70% of all PE and a large proportion of maternal-fetal morbidity related with this condition. Prediction and prevention of term PE remains unsolved.
- Previously proposed approaches are based on combined screening and/or prophylactic drugs, but these policies are unlikely to be implementable in many world settings.
- Recent evidence shows that sFlt1-PlGF ratio at 35-37w predicts term PE with 80% detection rate.
- Likewise, recent studies demonstrate that induction of labor (IOL) from 37w is safe.
- The investigators hypothesize that a single-step universal screening for term PE based on sFlt1/PlGF ratio at 35-37w followed by IOL from 37w would reduce the prevalence of term PE without increasing cesarean section rates or adverse neonatal outcomes.
- The investigators propose a randomized clinical trial to evaluate the impact of a screening of term PE with sFlt-1/PlGF ratio in asymptomatic nulliparous women at 35-37w. Women will be assigned to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cutoff of >90th centile will be used to define high risk of PE and offer IOL from 37w.
- If successful, the results of this trial will provide evidence to support a simple universal screening strategy reducing the prevalence of term PE, which could be applicable in most healthcare settings and have enormous implications on perinatal outcomes and public health policies worldwide.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Preeclampsia Intrauterine Growth Restriction Maternal Hypertension Neonatal Outcome Perinatal Death | Diagnostic Test: sFlt1/PlGF screening in maternal blood at 35 to 37 weeks of gestation | Not Applicable |
Finding an effective prediction and prevention for term PE remains an unsolved challenge. From previous recent evidence it seems clear that prediction very close to term may achieve a high detection rate, but there is no evidence as to which strategy might be effective in preventing PE in high-risk women. The investigators postulate that a solution that would be applicable in most settings worldwide would require a simplified, pragmatic, approach. The rationale of this proposal is that PE could be reduced with a single-step lab test screening followed by induction of labor (IOL).
A single-step lab measure to detect PE. Combined algorithms using angiogenic factors with Doppler ultrasound and maternal features seem to achieve the highest performance in detecting pre-clinical PE. However, the need to train staff and change pregnancy care protocols renders difficult generalization in high-resource and even more low-resource settings. On the contrary, single lab tests can be more easily incorporated into the mainstream clinical practice and provide a widespread solution for high-resource settings and specially sub-optimal healthcare systems heavily affected by the consequences of term PE. Angiogenic factors are the obvious candidate for these purposes. The sFlt1/PlGF ratio at 35-36w predicts term PE with a DR of 82% and is a standardized lab test nowadays, realizable by ELISA with widely available automated lab platforms. Normal values in late pregnancy have been reported and are fairly similar among different populations. As preliminary research for this study, the investigators have confirmed that the gestational-age adjusted normal values of sFlt1/PlGF matched quite remarkably those previously published in different populations across Europe. A one-step screening with sFlt1/PlGF would select a 5-10% of the population with the highest risk for PE.
IOL at 37 weeks as an intervention in women at high-risk for PE. Previous trials based on statins have failed to show a reduction of PE in high-risk women. IOL at 37 weeks is an alternative to avoid PE in those high-risk women. IOL has consistently been demonstrated to be safe ( ) and does not affect long-term maternal quality of life ( ). Both the HYPITAT and the DIGITAT randomized trials showed that IOL did not increase caesarean rates or adverse neonatal outcomes ( ). A recent large randomized trial in the US has shown that even in low-risk women, universal IOL decreased cesarean section rates and was well accepted ( ). While in low-risk pregnancies labour induction has been found to be beneficial from 39 weeks (ARRIVE study), in women with placental-related conditions such as hypertension (HYPITAT) or small-for-gestational age (DIGITAT) it is 37+ weeks when the trade-off between neonatal and maternal benefits makes induction recommendable.
Therefore, the investigators hypothesize that a single-step universal screening for term PE based on sFlt1/PlGF ratio at 35-36.6 w followed by IOL at 37w in those women found to be at high risk might represent a feasible and reproducible strategy, applicable worldwide, to reduce the prevalence of term PE without increasing cesarean section rates or adverse neonatal outcomes.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 9132 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Prospective, open-label randomized study with parallel groups. |
| Masking: | Double (Participant, Care Provider) |
| Masking Description: | Upon agreement to participate in this study, patients will be randomized to one of the following groups: • Intervention group or reveal group (sFlt-1/PlGF result known to clinicians). A ratio cutoff of >p90th will be used to define low and elevated risk of developing a placental complications of pregnancy and therefore induction of labour will be offered from 37th weeks of gestation Non-intervention or non-reveal (result unknown) group: routine follow-up and spontaneous delivery |
| Primary Purpose: | Prevention |
| Official Title: | PE37: A Multicenter Randomized Trial of Screening With sFlt1/PlGF and Selective Labor Induction to Prevent Preeclampsia at Term |
| Actual Study Start Date : | March 2, 2021 |
| Estimated Primary Completion Date : | December 31, 2022 |
| Estimated Study Completion Date : | December 31, 2023 |
| Arm | Intervention/treatment |
|---|---|
|
No Intervention: Non-intervention or non-reveal group
Non-intervention or non-reveal (result unknown) group: routine follow-up and spontaneous delivery
|
|
|
Experimental: Intervention group or reveal group
A ratio cutoff of >p90th will be used to define low and elevated risk of developing a placental complications of pregnancy and therefore induction of labour will be offered from 37th weeks of gestation
|
Diagnostic Test: sFlt1/PlGF screening in maternal blood at 35 to 37 weeks of gestation
A ratio cutoff of >p90th will be used to define low and elevated risk of developing a placental complications of pregnancy and therefore induction of labour will be offered from 37th weeks of gestation |
- Rate of Preeclampsia development [ Time Frame: 4 weeks ]Number of participants with preeclampsia/total number participants.
- Maternal morbidity rate [ Time Frame: 6 weeks ]Composite including any of the following: (i) HELLP syndrome; (ii) Central nervous system dysfunction (eclampsia, Glasgow Coma Score <13, stroke, reversible ischemic neurological deficit or cortical blindness); (iii) hepatic dysfunction; (iv) renal dysfunction; (v) respiratory dysfunction; (vi) cardiovascular dysfunction; (vii) placental abruption; or, (viii) a requirement for transfusion of blood products according to the total deliveries.
- Maternal Hospital stay [ Time Frame: 6 weeks ]Days of admission
- Caesarean section rate [ Time Frame: 4 weeks ]number of c-section / total deliveries
- Perinatal complications rate [ Time Frame: 18 weeks ]Presence of placental abruptio, severe fetal growth restriction (defined as birth weight <3rd centile), perinatal mortality, an Apgar score at 5-minute below 7.0, an umbilical artery pH below 7.10, need for respiratory support within 72 hours after birth neonatal intraventricular haemorrhage grade III/IV, necrotizing enterocolitis, periventricular leukomalacia, sepsis, bronchopulmonary dysplasia or hypoxic ischemic encephalopathy/total deliveries.
- Neonatal hospital stay [ Time Frame: 18 weeks ]Days
- Maternal experience [ Time Frame: 12 weeks ]Satisfaction score (PSS, STAI, WHO and Labor Agentry scale).
- Incurred costs [ Time Frame: 6 weeks ]Calculated costs
- Number of participants with Cardiovascular risk [ Time Frame: 6 months post-delivery ]Maternal blood pressure and endothelial function 6-months postpartum/ participants
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Gender Based Eligibility: | Yes |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Nulliparous women
- Singleton pregnancies
- >18 years old
- 35.0-36.6 weeks of gestation
- Maternal written consent form
- Planned vaginal delivery
Exclusion Criteria:
• Any maternal or fetal complications that require labor induction before 38 weeks according to local institutional protocols (including established preeclampsia).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04766866
| Contact: Elisa Llurba, MD; PhD | 0034687743699 | ellurba@santpau.cat |
| Belgium | |
| CHU Liège | Recruiting |
| Liège, Belgium | |
| Contact: Frederic Chantraine | |
| Czechia | |
| Institute for the Care of Mother and Child | Recruiting |
| Prague, Czechia | |
| Contact: Ladislav Kofta | |
| Poland | |
| Centre of Postgraduate Medical Education, Obstetrics and Gynecology and Perinatal Medicine | Recruiting |
| Warsaw, Poland | |
| Contact: Anna Kajdy | |
| Spain | |
| Hospital Germans Trias i Pujol | Recruiting |
| Badalona, Barcelona, Spain | |
| Contact: Mina Comas, PhD minacomas.germanstrias@gencat.cat | |
| Complejo Hospitalario Universitario Insular Materno Infantil | Not yet recruiting |
| Las Palmas De Gran Canaria, Islas Canarias, Spain | |
| Contact: Leonor Valle leonorvalle@yahoo.es | |
| Virgen de la Arrixaca | Not yet recruiting |
| El Palmar, Murcia, Spain, 30120 | |
| Contact: Jose Luís Delgado juanluisdelgado.tokos@gmail.com | |
| Hospital de la Santa Creu i Sant Pau | Recruiting |
| Barcelona, Spain | |
| Contact: Elisa Llurba | |
| Hospital del Mar | Recruiting |
| Barcelona, Spain | |
| Contact: Toni Payà | |
| Hospital Maternitat del Clínic | Recruiting |
| Barcelona, Spain | |
| Contact: Francesc Figueras ffiguera@clinic.cat | |
| Hospital Sant Joan de Déu | Recruiting |
| Barcelona, Spain | |
| Contact: Francesc Figueras | |
| Hospital La Paz | Not yet recruiting |
| Madrid, Spain | |
| Contact: José Luis Bartha | |
| Hospital Son Llatzer | Recruiting |
| Palma De Mallorca, Spain | |
| Contact: Albert Tubau | |
| Hospital la Fe | Recruiting |
| Valencia, Spain | |
| Contact: Alfredo Perales | |
| Hospital Lozano Blesa | Not yet recruiting |
| Zaragoza, Spain | |
| Contact: Daniel Oros | |
Documents provided by Elisa Llurba, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau:
| Responsible Party: | Elisa Llurba, Professor of Obstetric and Gynecology Universitat Autònoma de Barcelona, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau |
| ClinicalTrials.gov Identifier: | NCT04766866 |
| Other Study ID Numbers: |
PE37 |
| First Posted: | February 23, 2021 Key Record Dates |
| Last Update Posted: | December 14, 2021 |
| Last Verified: | December 2021 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
|
Preeclampsia, angiogenic factors, perinatal death, induction of labour |
|
Pre-Eclampsia Fetal Growth Retardation Perinatal Death Death Pathologic Processes |
Hypertension, Pregnancy-Induced Pregnancy Complications Fetal Diseases Growth Disorders |