Esomeprazole for the Prevention of Preeclampsia

NCT03717740 | Unknown Phase 3

• 1 other identifier: aswu/291/9/18
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

Preeclampsia, one of the hypertensive disorders of pregnancy, remains a leading cause of maternal death worldwide, with the majority of deaths occurring in developing countries. Preeclampsia is a multi-organ syndrome of pregnancy that manifests after 20 weeks' gestation with new-onset hypertension alongside maternal end-organ dysfunction and/or fetal growth restriction. Importantly, preeclampsia poses serious health risks for the baby, implicated in 12% of cases of fetal growth restriction, and is a known antecedent in up to 19% of preterm births. There is currently no effective treatment for preeclampsia except delivery of the baby, and as such, it remains a significant burden of disease for both mothers and their babies worldwide. Screening for women at risk of preeclampsia is an important part of antenatal care. Once women are identified as high risk, they can be targeted for more intensive antenatal surveillance and prophylactic interventions. Most current strategies for risk assessment are based on obstetric and medical history and clinical examination. However, there is surprisingly little reliable evidence on the actual risk associated with individual factors and how they might interact. Risk factors with a particularly high association with preeclampsia (more than one in ten risks) include maternal diabetes, chronic hypertension, and renal disease. Thrombophilia and autoimmune disease have a strong association with severe early-onset preeclampsia. Obstetric factors associated with high risk are multiple pregnancies, history of preeclampsia in a previous pregnancy especially if severe or early onset, and a current hydropic pregnancy. Other factors linked with preeclampsia but associated with a somewhat lower risk include first pregnancies, age less than 20 or more than 35 years, a family history of preeclampsia, and obesity. Proton pump inhibitors such as esomeprazole have long-term safety data about the treatment of gastric reflux in pregnancy. In vitro studies show proton pump inhibitors decrease soluble fems like tyrosine kinase -1 (sFlt-1) and soluble endoglin and improve markers of endothelial dysfunction . while esomeprazole reduces blood pressure in a preeclampsia transgenic mouse model that overexpresses sFlt-1.

Conditions

Pre-Eclampsia

Keywords

preeclampsia; esomeprazole; Soluble Fms Like Tyrosine Kinase -1

Outcome Measures

Primary Outcomes (1)

• Number of Participants With early onset Preeclampsia

  The number of cases of preeclampsia that appear in both groups before 34 weeks of pregnancy.Blood pressure greater than 140/90 on 2 occasions 6 hrs apart and significant proteinuria (greater than 300 mg in 24 hrs) before 34 weeks gestation

  6 months

Secondary Outcomes (3)

• Prevention of preeclampsia between 37 and 41

  6 months

• The number of cases of Fetal Growth Restriction

  6 months

• The number of cases of preterm birth

  6 months

Study Arms (2)

Esomeprazole

EXPERIMENTAL

Patients will take esomeprazole single dose of 40 mg orally once a day from 12+ and 17 weeks of pregnancy until 34 weeks of pregnancy,

Drug: Esomeprazole

Placebo

PLACEBO COMPARATOR

Patients will take Placebo Oral Tablet once a daily oral tablet from 12+ and 17 weeks of pregnancy until 34 weeks of pregnancy,

Drug: Placebo

Interventions

Esomeprazole DRUG

Patients will take esomeprazole single dose of 40 mg orally once a day from 12+ and 17 weeks of pregnancy until 34 weeks of pregnancy

Also known as: Experimental

Esomeprazole

Placebo DRUG

Patients will take an inert tablet similar in appearance, color, and consistency from 12+ and 17 weeks of pregnancy until 34 weeks of pregnancy

Also known as: Placebo Comparator

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: The population of interest involves women attending the study hospital for antenatal care and delivery
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnant women presenting prior to 17+0 weeks' gestation.
• Moderate to high risk of preeclampsia. One or more of the following: previous history of preeclampsia, antiphospholipid antibodies, pre-existing diabetes, pre-existing hypertension, pre-existing renal disease, autoimmune disease, nulliparity, family history of preeclampsia, elevated BMI \> 25, and maternal age \<20 or \>35.
• Give written informed consent.

You may not qualify if:

• Multiple pregnancies.
• Current or previous esomeprazole ingestion within the last 6 weeks.
• Previous hypersensitivity reaction esomeprazole
• Contraindications to the use of a proton pump inhibitor

Sponsors & Collaborators

• Aswan University Hospital: lead

Study Sites (1)

Aswan University

Aswān, 81528, Egypt

RECRUITING

MeSH Terms

Conditions

Pre-Eclampsia

Interventions

Esomeprazole

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• hany f sallam, md

  Aswan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

hany f sallam, md

CONTACT

01022336052; hany.farouk@aswu.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: both participants and researchers will be blinded to the intervention given.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The population of interest involves women attending the study hospital for antenatal care and delivery. The intervention involves randomization to oral esomeprazole tablets40 mg or identical placebo tablet from recruitment until delivery. Randomization is achieved using computational random allocation, and both participants and researchers will be blinded to the intervention given.

Study Record Dates

• First Submitted: October 22, 2018
• First Posted: October 24, 2018
• Study Start: December 1, 2018
• Primary Completion: November 30, 2021
• Study Completion: January 1, 2022
• Last Updated: January 10, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)