Esomeprazole in Treatment of Early Onset Preeclampsia (ESOPE Trial)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Use of Esomeprazole in Treatment of Early Onset Preeclampsia:a Double Blind Randomized, Placebo-controlled Trial

Conditions
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Preeclampsia

Intervention / Treatment
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* Drug: Esomeprazole 40 mg Oral Tablet
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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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. 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

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: study group<br>Patients will take esomeprazole single dose of 40 mg orally once a day | Drug: Esomeprazole 40 mg Oral Tablet<br>* once daily oral tablets<br>* Other names: Nexium;|
| Placebo Comparator: control group<br>Patients will take an inert tablet similar in appearance, color and consistency | Drug: Placebo Oral Tablet<br>* once daily oral tablets<br>* Other names: inert;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prolongation of gestation measured from the time of enrollment to the time of delivery |  | 2 weeks | 
| The side effects of the drugs |  | 2 weeks |