Esomeprazole With Sildenafil Citrate in Women With Early-onset Preeclampsia

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

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.

Study Overview

• Status: Unknown
• Conditions: Preeclampsia
• Intervention / Treatment: Drug: Esomeprazole with Sildenafil Citrate; Drug: Sildenafil Citrate; Drug: Placebo to Sildenafil Citrate; Drug: Placebo to Esomeprazole

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Aswan, Egypt, 81528
    • Recruiting
    • Aswan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Esomeprazole with Sildenafil Citrate; 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; Patients will take esomeprazole single dose of 40 mg orally once a day; Other Names: Active Comparator; Drug: Sildenafil Citrate; Patients will take Sildenafil Citrate 40mg every 8 hours; Other Names: active comparator
Active Comparator: Esomeprazole alone plus placebo to Sildenafil Citrate; 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; Patients will take esomeprazole single dose of 40 mg orally once a day; Other Names: Active Comparator; Drug: Placebo to Sildenafil Citrate; Patients will take inert tablets similar in appearance, color, and consistency to Sildenafil Citrate 40mg every 8 hours
Placebo Comparator: placebo to Esomeprazole plus placebo to Sildenafil Citrate; 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 Sildenafil Citrate; Patients will take inert tablets similar in appearance, color, and consistency to Sildenafil Citrate 40mg every 8 hours; Drug: Placebo to Esomeprazole; Patients will take inert tablets similar in appearance, color, and consistency to esomeprazole single dose of 40 mg orally once a day

What is the study measuring?

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
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
Side effects	any side effects or adverse events related to the intervention, intervention stopped due to side effects	4 weeks

Collaborators and Investigators

• Sponsor: Aswan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Anticipated): November 30, 2021
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: October 29, 2018
• First Submitted That Met QC Criteria: October 29, 2018
• First Posted (Actual): October 30, 2018

Study Record Updates

• Last Update Posted (Actual): January 10, 2019
• Last Update Submitted That Met QC Criteria: January 8, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Esomeprazole; Sildenafil Citrate; preterm preeclampsia
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anticoagulants; Anti-Ulcer Agents; Proton Pump Inhibitors; Phosphodiesterase Inhibitors; Chelating Agents; Sequestering Agents; Phosphodiesterase 5 Inhibitors; Calcium Chelating Agents; Sildenafil Citrate; Esomeprazole; Citric Acid; Sodium Citrate
• Other Study ID Numbers: aswu 193/7/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No