Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04766866 |
| Other study ID # |
PE37 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 2, 2021 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
November 2023 |
| Source |
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau |
| Contact |
Elisa Llurba, MD; PhD |
| Phone |
0034687743699 |
| Email |
ellurba[@]santpau.cat |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
- 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.
Description:
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.
Individual participant data, study protocol, statistical analysis plan and informed consent
form will be available with publication by email addresses after approval of a proposal with
a signed data access agreement
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