Clinical trial NCT03213639: Esomeprazole in Treatment of Early Onset Preeclampsia (ESOPE Trial)
Official title: Use of Esomeprazole in Treatment of Early Onset Preeclampsia:a Double Blind Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Preeclampsia
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2017-07-11
Enrollment: 205
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of women who develop HELLP syndrome
timeFrame: 1 month
measure: The change in serum level of sFlt-1 and endoglin before the start of treatment and at termination of pregnancy
timeFrame: 2 weeks
Secondary outcomes:
measure: Prolongation of gestation measured from the time of enrollment to the time of delivery
timeFrame: 2 weeks
measure: The side effects of the drugs
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut Faculty of Medicine
Study officials:
affiliation: Assiut University
name: Ahmed Abbas, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.