PreeclampsiaPhase 2/3NCT03213639
Esomeprazole in Treatment of Early Onset Preeclampsia (ESOPE Trial)
A Phase 2/3 study testing Esomeprazole 40 mg Oral Tablet in people with Preeclampsia, run by Assiut University at 1 site in Egypt.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Preeclampsia
- What is being tested?
- Esomeprazole 40 mg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 205 participants
- Where
- 1 siteEgypt
- Study dates
- 15 Mar 2018to 15 Oct 2020
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Use of Esomeprazole in Treatment of Early Onset Preeclampsia:a Double Blind Randomized, Placebo-controlled Trial
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.
Read the 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
- Being tested
- Esomeprazole 40 mg Oral Tablet, Placebo Oral Tablet
- Medical subject headings
- Pre-Eclampsia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esomeprazole 40 mg Oral TabletDrug
Also called Nexium
once daily oral tablets
Placebo Oral TabletDrug
Also called inert
once daily oral tablets
| Study group | Role | What they receive |
|---|---|---|
| study group | Experimental | Patients will take esomeprazole single dose of 40 mg orally once a day Receives: Drug: Esomeprazole 40 mg Oral Tablet |
| control group | Placebo comparator | Patients will take an inert tablet similar in appearance, color and consistency Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of women who develop HELLP syndrome
Measured: 1 month
The change in serum level of sFlt-1 and endoglin before the start of treatment and at termination of pregnancy
Measured: 2 weeks
Secondary outcomes (2)
Prolongation of gestation measured from the time of enrollment to the time of delivery
Measured: 2 weeks
The side effects of the drugs
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2017
- Study start15 Mar 2018
- Primary completion1 Jul 2020
- Study completion15 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PreeclampsiaStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 205 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmed Mohamed Abbas, Assiut University
- Investigators
- Ahmed Abbas, MD, Study director, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03213639
- Sponsor's protocol ID
- ESOPE
- Status last verified
- Jan 2021
- First submitted
- 8 Jul 2017
- Last updated
- 7 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26510725Lagana 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.
PubMed 26512423Baumann 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.
PubMed 18771978
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Esomeprazole in Treatment of Early Onset Preeclampsia:a Double Blind Randomized, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT03213639
- Acronym / sponsor ID
- ESOPE
- Conditions
- Preeclampsia
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 205 participants (actual)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 15 Mar 2018 (actual)
- Primary completion
- 1 Jul 2020 (actual)
- Study completion
- 15 Oct 2020 (actual)
- First posted
- 11 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| study group | Experimental | Drug: Esomeprazole 40 mg Oral TabletPatients will take esomeprazole single dose of 40 mg orally once a day |
| control group | Placebo comparator | Drug: Placebo Oral TabletPatients will take an inert tablet similar in appearance, color and consistency |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Esomeprazole 40 mg Oral TabletAlso: Nexiumonce daily oral tablets | Drug | study group |
| Placebo Oral TabletAlso: inertonce daily oral tablets | Drug | control group |
Primary outcome
Number of women who develop HELLP syndrome
Time frame: 1 month
The change in serum level of sFlt-1 and endoglin before the start of treatment and at termination of pregnancy
Time frame: 2 weeks
2 secondary outcomes
Prolongation of gestation measured from the time of enrollment to the time of delivery
Time frame: 2 weeks
The side effects of the drugs
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2021.
- Background: PubMed 26510725Cluver 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.
- Background: PubMed 26512423Lagana 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.
- Background: PubMed 18771978Baumann 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahmed Abbas, MD study director
Assiut University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Esomeprazole 40 mg Oral Tablet in people with Preeclampsia, run by Assiut University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of women who develop HELLP syndrome (time frame: 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03213639, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2021.