Esomeprazole With Sildenafil Citrate in Women With Early-onset Preeclampsia

Study Overview
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Brief Summary
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Previous studies have shown that expectant management of preeclampsia 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. In this study, we evaluate the use of Esomeprazole alone or with Sildenafil Citrate for the treatment of singleton pregnancies complicated by preeclampsia. We hypothesized that the potential increase in uteroplacental and fetoplacental blood flow with the use of Esomeprazole alone or with Sildenafil Citrate may be associated with pregnancy prolongation (the primary study outcome) and improved maternal and perinatal outcomes.

Detailed Description
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The etiology and pathophysiology of preeclampsia have not been clearly established; impaired immunologic adaptation and genetic incompatibility seem to be involved in deficient trophoblastic implantation. Placental hypoxia and endothelial dysfunction may lead to preeclampsia through an exacerbated systemic inflammatory reaction. Increased placental expression and secretion of soluble fms-like tyrosine kinase 1 appear to play a central role in the pathogenesis of preeclampsia. The soluble fms-like tyrosine kinase 1 antagonizes the proangiogenic biologic activity of circulating vascular endothelial growth factor and placental growth factor, leading to a failure of nitric oxide signaling to smooth muscle The investigators will conduct a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of Esomeprazole alone or with Sildenafil Citrate in preterm pregnancies complicated by preeclampsia.

Official Title
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Esomeprazole Alone or With Sildenafil Citrate in Women With Early-onset Preeclampsia: A Randomized Controlled Trial

Conditions
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Preeclampsia

Intervention / Treatment
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* Drug: Esomeprazole with Sildenafil Citrate
* Drug: Sildenafil Citrate
* Drug: Placebo to Esomeprazole
* Drug: Placebo to Sildenafil Citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women presenting at a Gestational age between 28 + 0 weeks and 32 + 0 weeks presented with preterm preeclampsia The patient will be managed with an expectant management Give written informed consent Exclusion Criteria: Multiple pregnancies. Previous hypersensitivity reaction esomeprazole or sildenafil citrate Contraindications to the use of esomeprazole or sildenafil citrate The patient is unable or unwilling to give consent An established fetal compromise that necessitates delivery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: We will conduct a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of Esomeprazole alone or with Sildenafil Citrate in preterm pregnancies complicated by preeclampsia.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Esomeprazole with Sildenafil Citrate<br>Patients will take esomeprazole single dose of 40 mg orally once a day plus three doses of Sildenafil Citrate 40mg orally every 8 hours | Drug: Esomeprazole with Sildenafil Citrate<br>* Patients will take esomeprazole single dose of 40 mg orally once a day<br>* Other names: Active Comparator;Drug: Sildenafil Citrate<br>* Patients will take Sildenafil Citrate 40mg every 8 hours<br>* Other names: active comparator;|
| Active Comparator: Esomeprazole alone plus placebo to Sildenafil Citrate<br>Patients will take esomeprazole single dose of 40 mg orally once a day plus three doses of placebo identical in shape and consistency withSildenafil Citrate 40mg orally every 8 hours | Drug: Esomeprazole with Sildenafil Citrate<br>* Patients will take esomeprazole single dose of 40 mg orally once a day<br>* Other names: Active Comparator;Drug: Placebo to Sildenafil Citrate<br>* Patients will take inert tablets similar in appearance, color, and consistency to Sildenafil Citrate 40mg every 8 hours<br>|
| Placebo Comparator: placebo to Esomeprazole plus placebo to Sildenafil Citrate<br>Patients will take placebo identical in shape and consistency with esomeprazole single dose of 40 mg orally once a day plus three doses of placebo identical in shape and consistency withSildenafil Citrate 40mg orally every 8 hours | Drug: Placebo to Esomeprazole<br>* Patients will take inert tablets similar in appearance, color, and consistency to esomeprazole single dose of 40 mg orally once a day<br>Drug: Placebo to Sildenafil Citrate<br>* Patients will take inert tablets similar in appearance, color, and consistency to Sildenafil Citrate 40mg every 8 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prolongation of gestation measured from the time of enrollment to the time of delivery. | Prolongation of gestation measured from the time of enrollment to the time of delivery | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe morbidity | Severe morbidity including eclampsia, liver or renal failure, hemolysis, elevated liver enzymes and low platelets syndrome (HELLP), disseminated intravascular coagulation (DIC), stroke, and pulmonary edema | 4 weeks | 
| Side effects | any side effects or adverse events related to the intervention, intervention stopped due to side effects | 4 weeks | 
| The change in serum level of sFlt-1 and endoglin before the start of treatment and at termination of pregnancy | The change in serum level of sFlt-1 and endoglin before the start of treatment and at termination of pregnancy | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esomeprazole, Sildenafil Citrate, preterm preeclampsia