Preeclampsia
Conditions
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.
Interventions
DRUGEsomeprazole 40 mg Oral Tablet
once daily oral tablets
DRUGPlacebo Oral Tablet
once daily oral tablets
Sponsors
Assiut University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
Egypt
Outcome results
None listed