Esomeprazole in Treatment of Early Onset Preeclampsia (ESOPE Trial)

Assiut University

Status and phase

Completed

Phase 3

Phase 2

Conditions

Preeclampsia

Treatments

Drug: Placebo Oral Tablet

Drug: Esomeprazole 40 mg Oral Tablet

Study type

Interventional

Funder types

Other

Identifiers

NCT03213639

ESOPE

Details and patient eligibility

About

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.

Full 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.

Enrollment

205 patients

Sex

Female

Ages

18 to 45 years old

Volunteers

No Healthy Volunteers

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