Esomeprazole in Treatment of Early Onset Preeclampsia (ESOPE Trial)

Phase 2

Completed

• Conditions: Preeclampsia
• Interventions: Drug: Esomeprazole 40 mg Oral Tablet; Drug: Placebo Oral Tablet

• Registration Number: NCT03213639
• Lead Sponsor: Assiut University

Brief Summary

Pre-eclampsia is one of the most serious complications of pregnancy affecting 3-8 % of pregnancies worldwide. It is a multi-system disorder involving maternal vessels (causing hypertension and endothelial dysfunction), the kidneys, the liver, the lungs, the hematological system, the cardiovascular system and the feto-placental unit. In its most severe form, it affects the brain, causing seizures (eclampsia), cerebro-vascular events and even death.

Detailed Description

The key aspects in the pathophysiology of pre-eclampsia are placental oxidative stress (and hypoxia), placental release of the anti-angiogenic factors Soluble Fms Like Tyrosine Kinase -1 and soluble endoglin and maternal endothelial dysfunction. A drug that can counter these pathological steps could be a strategy to treat pre-eclampsia.

If an affordable and safe treatment was available it could temporize the disease progression of pre-eclampsia thereby delaying delivery to gain gestation. This could save the lives of many infants and decrease the hospital burden caused by iatrogenic prematurity.

Currently, there are trials investigating the possible use of pravastatin to treat pre-eclampsia, and to prevent it There are no other significant trials of orally available small molecules to treat pre-eclampsia that we are aware of.

The Translational Obstetrics Group at Melbourne University has generated strong preclinical evidence suggesting esomeprazole as one of the proton pump inhibitors may have potent actions giving it significant potential as a treatment for pre-eclampsia

Proton pump inhibitors have been commonly used in pregnancy to treat gastroesophageal reflux disorders and more serious gastrointestinal complications like Helicobacter pylori-infection, peptic and duodenal ulcers and Zollinger-Ellison syndrome.

Esomeprazole counters three key steps in pre-eclampsia pathogenesis, by up-regulating heme oxygenase-1 ( strongly decreasing the release of antiangiogenic factors Soluble Fms Like Tyrosine Kinase -1 and soluble endoglin and quenching endothelial dysfunction.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-07-08
• Study First Submitted QC: 2017-07-08
• Study First Posted: 2017-07-11
• Study Start: 2018-03-15
• Primary Completion: 2020-07-01
• Study Completion: 2020-10-15
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-06
• Last Update Posted: 2021-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 205

Inclusion Criteria

• Gestational age between 28 + 0 weeks and 31 + 6 weeks
• Estimated fetal weight by ultrasound between 500 gm and 1800 gm (if gestation is not certain).
• Singleton pregnancy.
• The patient will be managed with expectant management.

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Exclusion Criteria

• Patient is unable or unwilling to give consent

• Established fetal compromise that necessitates delivery.

• The presence of any of the following at presentation:

  • Eclampsia.
  • Severe hypertension.
  • Cerebrovascular event as an ischaemic or haemorrhagic stroke.
  • Renal impairment.
  • Signs of left ventricular failure which include pulmonary oedema.
  • Disseminated intravascular coagulation (DIC)
  • Haemolysis, elevated liver enzymes and low platelets (HELLP syndrome)
  • Fetal distress on cardiotocography

• Contra-indications for expectant management of pre-eclampsia

• Current use of a proton pump inhibitor

• Contraindications to the use of a proton pump inhibitor

• Previous hypersensitivity reaction to a proton pump inhibitor

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
study group	Esomeprazole 40 mg Oral Tablet	Patients will take esomeprazole single dose of 40 mg orally once a day
control group	Placebo Oral Tablet	Patients will take an inert tablet similar in appearance, color and consistency

Primary Outcome Measures

Name	Time	Method
The change in serum level of sFlt-1 and endoglin before the start of treatment and at termination of pregnancy	2 weeks
Number of women who develop HELLP syndrome	1 month

Secondary Outcome Measures

Name	Time	Method
Prolongation of gestation measured from the time of enrollment to the time of delivery	2 weeks
The side effects of the drugs	2 weeks

Trial Locations

Locations (1)

Assiut Faculty of Medicine; 🇪🇬 Assiut, Egypt