Metformin and Esomeprazole in Treatment of Early Onset Preeclampsia

Combining Metformin and Esomeprazole in Treatment of Early Onset Preeclampsia: A Double-Blind Randomized, Placebo-controlled Trial

Preeclampsia is globally responsible for tens of thousands of maternal and neonatal deaths each year. Currently, there are no medical therapies to halt disease progression and expectant management and delivery remain the mainstay of treatment. An important step in the pathogenesis of preeclampsia is a poor placental invasion and the subsequent release of the anti-angiogenic factors soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng)into the maternal circulation. Given metformin and esomeprazole successfully mitigate key pathogenic features of preeclampsia, the investigator will study whether combining low-doses of metformin and esomeprazole may be additive or synergistic (or neither) in reducing sFlt-1 and sEng secretion, and mitigating endothelial dysfunction, compared to placebo.

Study Overview

• Status: Unknown
• Conditions: Pre-Eclampsia
• Intervention / Treatment: Drug: metformin; Drug: esomeprazole; Drug: Placebo

Detailed Description

This is a randomized double-blinded placebo-controlled intervention trial investigating preeclampsia, defined according to the International Society for the Study of Hypertension in Pregnancy (ISSHP). The population of interest involves pregnant women diagnosed with pre-eclampsia at a gestational age between 28 and 32 weeks at Aswan university hospital will be invited to participate. To be enrolled, the treating team needs to have determined after their initial assessment that delivery is unlikely to be required within 48 h. A starting point of 28 weeks has been chosen as this would be the earliest gestation that Aswan university hospital to be viable and are suitable to be offered expectant management The intervention involves randomization to oral esomeprazole tablets40 mg plus metformin tablets 1000 mg or identical placebo tablets from recruitment until delivery. Randomization is achieved using computational random allocation, and both participants and researchers will be blinded to the intervention given.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Aswan, Egypt, 81528
    • Recruiting
    • Aswan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant women presenting at a Gestational age between 28 + 0 weeks and 32 + 0 weeks presented with preterm preeclampsia
• The patient will be managed with an expectant management
• Give written informed consent

Exclusion Criteria:

• Multiple pregnancies.
• Previous hypersensitivity reaction esomeprazole or metformin
• Contraindications to the use of esomeprazole or metformin
• The patient is unable or unwilling to give consent
• An established fetal compromise that necessitates delivery

• The presence of any of the following at presentation:

  • Eclampsia.
  • Severe hypertension.
  • A cerebrovascular event as an ischemic or hemorrhagic stroke.
  • Renal impairment.
  • Signs of left ventricular failure which include pulmonary edema.
  • Disseminated intravascular coagulation (DIC)
  • Haemolysis, elevated liver enzymes and low platelets (HELLP syndrome)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: metformin and esomeprazole; Patients will take esomeprazole single dose of 40 mg orally once a day plus single dose of metformin 1000mg orally single dose once a day	Drug: metformin; Patients will take metformin single dose of 1000 mg orally once a day; Other Names: Experimental; Drug: esomeprazole; Patients will take esomeprazole single dose of 40 mg orally once a day; Other Names: Experimental
Placebo Comparator: Placebo; Patients will take inert tablets similar in appearance, color, and consistency	Drug: Placebo; Patients will take inert tablets similar in appearance, color, and consistency

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prolongation of gestation measured from the time of enrollment to the time of delivery.	Prolongation of gestation measured from the time of enrollment to the time of delivery.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe morbidity	Severe morbidity including eclampsia, liver or renal failure, hemolysis, elevated liver enzymes and low platelets syndrome (HELLP), disseminated intravascular coagulation (DIC), stroke, and pulmonary edema	4 weeks
The change in serum level of sFlt-1 and endoglin before the start of treatment and at termination of pregnancy	The change in serum level of sFlt-1 and endoglin before the start of treatment and at termination of pregnancy	4 weeks
Side effects	any side effects or adverse events related to the intervention, intervention stopped due to side effects	4 weeks

Collaborators and Investigators

• Sponsor: Aswan University Hospital
• Investigators: Principal Investigator: hany f sallam, Aswan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Anticipated): November 30, 2020
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: October 22, 2018
• First Posted (Actual): October 24, 2018

Study Record Updates

• Last Update Posted (Actual): January 10, 2019
• Last Update Submitted That Met QC Criteria: January 8, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: metformin; esomeprazole; preeclampsia
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Eclampsia; Pre-Eclampsia; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Metformin; Esomeprazole
• Other Study ID Numbers: aswu/273/9l18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No