Metformin and Esomeprazole For Preterm Pre-eclampsia

Use of Combination Metformin and Esomeprazole in Preterm Pre- Eclampsia: Randomized Controlled Trial

A recent randomized controlled trial by Cluver et al included 180 women with preterm pre-eclampsia between 26+0 to 31+6 weeks' gestation undergoing expectant management: 90 were randomised to extended release metformin and 90 to placebo. Investigators found that extended release metformin (3g daily) can prolong gestation in women with preterm pre-eclampsia. Combination metformin and esomeprazole has shown promise in the treatment of preeclampsia as both agents reduce placental and endothelial secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin, and reduce endothelial dysfunction.

Study Overview

• Status: Not yet recruiting
• Conditions: Preterm Birth Complication; Preeclampsia Severe; Preeclampsia Second Trimester
• Intervention / Treatment: Drug: Esomeprazole 20mg

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Health Systems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Individuals presenting with pre-eclampsia between 24+0 and 31+6 weeks of gestation, with a single viable fetus and no major anomalies

• Women 18 years or older
• Women diagnosed with preeclampsia
• Women with pre-eclampsia superimposed on chronic hypertension
• Candidates for expectant management and had no clinical indication for immediate delivery

Exclusion Criteria:

• Delivery within 48hr is highly likely
• Maternal or fetal compromise that necessitated immediate delivery
• Diabetes or gestational diabetes currently on metformin therapy
• Contraindications to metformin, esomeprazole
• Baseline creatinine >124 μmol/L
• Hypersensitivity to metformin or esomeprazole
• Metabolic acidosis
• Use of drugs that might interact with metformin (glyburide, furosemide, or cationic drugs) Multiple gestations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: combination metformin and esomeprazole; Combination 2 g of oral extended release metformin, in divided doses and Esomeprazole 20mg daily until delivery.	Drug: Esomeprazole 20mg; Combination 2 g of oral extended release metformin, Esomeprazole 20mg daily until delivery.; Other Names: Metformin
NO_INTERVENTION: expectant management

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
mean plasma difference in sFlt-1 from randomization to day 7	from randomization to day 7

Secondary Outcome Measures

Outcome Measure	Time Frame
Gestational age at delivery	at time of delivery
Mean plasma difference in vascular endothelial growth factor (VEGF)	from randomization to day 7
Mean plasma difference in placental growth factor (PlGF) levels	from randomization to day 7
Mean plasma difference in soluble endoglin (sEng)	from randomization to day 7
Maternal death	At time of delivery
Mean highest blood pressure during expectant management mmHg	At time of delivery
Number of anti-hypertensive medications at delivery	at time of delivery
Fetal growth restriction defined as a sonographic estimated fetal weight (EFW) or abdominal circumference (AC) below the 10th percentile for gestational age using Hadlock cutoffs	at time of delivery
Neonatal intensive care unit (nicu) admission	at time of delivery

Collaborators and Investigators

• Sponsor: Christiana Care Health Services

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2023
• Primary Completion (ANTICIPATED): December 31, 2024
• Study Completion (ANTICIPATED): December 31, 2025

Study Registration Dates

• First Submitted: January 31, 2022
• First Submitted That Met QC Criteria: January 31, 2022
• First Posted (ACTUAL): February 10, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Hypertension, Pregnancy-Induced; Premature Birth; 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: DDD# 605095

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Data are available for 5 years at a third party website
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No