Pre-Eclampsia; Mild Clinical Trial
Official title:
Use of Sildenafil Citrate in Management of Mild Pre-eclampsia: A Randomized Controlled Trial
- Mild pre-eclampsia represents 75% of cases with pre-eclampsia, possible progression to
severe pre-eclampsia makes mild pre-eclampsia a serious problem that requires attention.
- Previous studies have shown that expectant and conservative management of pre-eclampsia
in the context of extreme prematurity may improve perinatal outcomes. Indeed, it has
been estimated that for each additional day of pregnancy prolongation between 24 and 32
weeks of gestation, there is a nonlinear corresponding gain of 1% in fetal survival.
- Sildenafil citrate has been used for increasing utero-placental perfusion in cases with
intrauterine growth restriction, which makes it a promising drug in management of mild
pre-eclampsia.
- Pre-eclampsia affects approximately 2-8% of all pregnancies worldwide. In Egypt, the
prevalence of pre-eclampsia is 10.7% in a community based study. While, in hospital based
studies it ranged from 9.1% to 12.5% of all deliveries. The incidence of pre-eclampsia has
risen in the developing countries and even in the developed countries as the USA since the
1990s. Among the hypertensive disorders that complicate pregnancy, pre-eclampsia and
eclampsia stand as major causes of maternal and perinatal morbidity and mortality worldwide.
Nearly one tenth of all maternal deaths in Africa and Asia and one quarter in Latin America
are associated with hypertensive diseases in pregnancy, a category that includes
pre-eclampsia and the complications that are related to it.
However, the pathogenesis of pre-eclampsia is only partially understood and it is related to
disturbances in placentation at the beginning of pregnancy, followed by generalized
inflammation and progressive endothelial damage. There are other uncertainties too: the
diagnosis, screening and management of pre-eclampsia remain controversial, as does the
classification and the degree of its severity.
However, it is generally accepted as published in the different journals and in the WHO
recommendations that the onset of a new episode of hypertension during pregnancy (with
persistent systolic blood pressure 140 mm Hg and diastolic blood pressure 90 mm Hg or more)
with the occurrence of substantial proteinuria (>0.3 g/24 h or confirmation of proteinuria by
semiquantitative urine dipstick analysis with a result of at least 1+) can be used as
criteria for identifying pre-eclampsia.
Although pathophysiological changes (e.g. inadequate placentation) exist from very early
stages of the pregnancy, hypertension and proteinuria usually become apparent in the second
half of pregnancy.
Complications of pre-eclampsia can affect both the mother and the fetus. Acutely,
pre-eclampsia can be complicated by eclampsia , the development of HELLP Syndrome ,
hemorrhagic or ischemic stroke, liver damage and dysfunction, acute kidney injury and Acute
Respiratory Distress Syndrome (ARDS).
So early detection of pre-eclampsia and prevention of the occurrence of any of its
complications would save the lives of many women and prevent the possible devastating
maternal and neonatal outcome of pre-eclampsia, That's why we are concerned in our study with
pre-eclampsia, covering the gestational age from 28 - 36 weeks.
Mild pre-eclampsia represents 75% of cases with pre-eclampsia, possible progression to severe
pre-eclampsia makes mild pre-eclampsia a serious problem that requires attention.
Previous studies have shown that expectant and conservative management of pre-eclampsia in
the context of extreme prematurity may improve perinatal outcomes. Indeed, it has been
estimated that for each additional day of pregnancy prolongation between 24 and 32 weeks of
gestation, there is a nonlinear corresponding gain of 1% in fetal survival.
Sildenafil citrate has been used for increasing utero-placental perfusion in cases with
intrauterine growth restriction, which makes it a promising drug in management of mild
pre-eclampsia.
Its action is similar to the action of nitric oxide, which is a potent vasodilator,
especially for the venules, besides being an inhibitor of platelet aggregation. During
pregnancy, nitric oxide is synthesized in in utero-placental tissues and endothelial cells,
helping to maintain low vascular resistance in the utero- and fetoplacental circulations.
Phosphodiesterase metabolizes cyclic guanosine monophosphate; therefore, phosphodiesterase
type 5 inhibition leads to cyclic guanosine monophosphate increase with associated
vasodilation, independently of nitric oxide. Therefore, phosphodiesterase type 5 inhibitors
have the potential to achieve similar therapeutic goals when compared with nitric oxide.
A potential advantage of phosphodiesterase type 5 inhibitors is that they may overcome the
main limitation to nitric oxide use in pregnancy, which is tolerance and headaches. The most
studied phosphodiesterase type 5 inhibitor is sildenafil citrate, which has previously shown
promising outcomes both in vitro and in animal studies.
That is why we decided to study the role of Sildenafil Citrate in expectant and conservative
management of mild pre-eclampsia, as it has shown its ability to be beneficial to both the
mother and the fetus through increasing the maternofetal circulation perfusion and achieving
a maternal hemodynamic stability and compare it to the current NICE (National Institute for
Health and Care Excellence) guidelines that are currently used, that recommends conservative
management of mild pre-eclampsia through control of maternal blood pressure and frequent
screening of maternal laboratory investigations' abnormalities to detect possible progression
to severe pre-eclamptic toxemia.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT03323762 -
Effect of RIC on BP and Inflammatory Response in Women With Pre-eclampsia
|
N/A |