Esomeprazole in Treatment of Early Onset Preeclampsia (ESOPE Trial)

NCT ID: NCT03213639

Last Updated: 2021-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 205 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-15
• Study Completion Date: 2020-10-15

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.

Conditions

Preeclampsia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

study group

Patients will take esomeprazole single dose of 40 mg orally once a day

Group Type: EXPERIMENTAL

Esomeprazole 40 mg Oral Tablet

Intervention Type: DRUG

once daily oral tablets

control group

Patients will take an inert tablet similar in appearance, color and consistency

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

once daily oral tablets

Interventions

Esomeprazole 40 mg Oral Tablet

once daily oral tablets

Intervention Type: DRUG

Placebo Oral Tablet

once daily oral tablets

Intervention Type: DRUG

Other Intervention Names

Nexium; inert

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Ahmed Mohamed Abbas

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ahmed Abbas, MD

Role: STUDY_DIRECTOR

Assiut University

Locations

Assiut Faculty of Medicine

Asyut, , Egypt

Countries

Egypt

References

Cluver CA, Walker SP, Mol BW, Theron GB, Hall DR, Hiscock R, Hannan N, Tong S. Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol. BMJ Open. 2015 Oct 28;5(10):e008211. doi: 10.1136/bmjopen-2015-008211.

Reference Type: BACKGROUND

PMID: 26510725 (View on PubMed)

Lagana AS, Favilli A, Triolo O, Granese R, Gerli S. Early serum markers of pre-eclampsia: are we stepping forward? J Matern Fetal Neonatal Med. 2016 Sep;29(18):3019-23. doi: 10.3109/14767058.2015.1113522. Epub 2015 Nov 23.

Reference Type: BACKGROUND

PMID: 26512423 (View on PubMed)

Baumann MU, Bersinger NA, Mohaupt MG, Raio L, Gerber S, Surbek DV. First-trimester serum levels of soluble endoglin and soluble fms-like tyrosine kinase-1 as first-trimester markers for late-onset preeclampsia. Am J Obstet Gynecol. 2008 Sep;199(3):266.e1-6. doi: 10.1016/j.ajog.2008.06.069.

Reference Type: BACKGROUND

PMID: 18771978 (View on PubMed)

Other Identifiers

ESOPE

Identifier Type: -

Identifier Source: org_study_id