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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| study group | Experimental | Patients will take esomeprazole single dose of 40 mg orally once a day |
|
| control group | Placebo Comparator | Patients will take an inert tablet similar in appearance, color and consistency |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Esomeprazole 40 mg Oral Tablet | Drug | once daily oral tablets |
|
| 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 |
| 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 |
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Inclusion Criteria:
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| Ahmed Abbas, MD | Assiut University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Assiut Faculty of Medicine | Asyut | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26510725 | Background | 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. | |
| 26512423 | Background |
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| ID | Term |
|---|---|
| D011225 | Pre-Eclampsia |
| ID | Term |
|---|---|
| D046110 | Hypertension, Pregnancy-Induced |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D064098 | Esomeprazole |
| D013607 | Tablets |
| D005741 | Noble Gases |
| ID | Term |
|---|---|
| D009853 | Omeprazole |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
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| Placebo Oral Tablet | Drug | once daily oral tablets |
|
|
| 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. |
| 18771978 | Background | 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. |
| D009930 |
| Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D005740 | Gases |