Metformin and Esomeprazole in Preterm Pre-eclampsia

NCT06359015 | Terminated Phase 4 DMC FDA Drug

• 2 other identifiers: 41138605095
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to better understand diagnosis and treatment of preterm preeclampsia. Currently, there are limited laboratory tests that can be used to diagnosis preeclampsia. Additionally, there are few treatments for this condition. This clinical trial will explore treatment options, Metformin and Esomeprazole, as well as serum markers that could improve the diagnosis and treatment of preterm preeclampsia.

Conditions

Preeclampsia Severe; Preeclampsia; Preeclampsia Second Trimester; Preeclampsia Complicating Childbirth; Preeclampsia Puerperium; Preterm

Keywords

Metformin; Esomeprazole; Preterm Preeclampsia; Preeclampsia with Severe Features; Superimposed Preeclampsia with Severe Features

Outcome Measures

Primary Outcomes (1)

• Mean plasma difference in sFlt-1

  sFlt-1 from serum samples

  Over the first 14 days after randomization and during the remainder of pregnancy, an average of 3-4 months

Secondary Outcomes (5)

• Mean plasma difference in vascular endothelial growth factor (VEGF)

  Over the first 14 days after randomization and during the remainder of pregnancy, an average of 3-4 months

• Mean plasma difference in placental growth factor (PIGF)

  Over the first 14 days after randomization and during the remainder of pregnancy, an average of 3-4 months

• Mean plasma difference in soluble endoglin (sEng)

  Over the first 14 days after randomization and during the remainder of pregnancy, an average of 3-4 months

• sFlt-1:PIGF ratio

  Over the first 14 days after randomization and during the remainder of pregnancy, an average of 3-4 months

• Prolongation of gestation

  Over the first 14 days after randomization and during the remainder of pregnancy, an average of 3-4 months

Study Arms (2)

Metformin and Esomeprazole

EXPERIMENTAL

Patients diagnosed with preterm preeclampsia receive expectant management with additional metformin/esomeprazole.

Drug: Metformin; Drug: Esomeprazole

No Intervention

NO INTERVENTION

Patients diagnosed with preterm preeclampsia receive expectant management only.

Interventions

Metformin DRUG

Oral Metformin schedule: Day 1: 500 milligrams in morning Day 2: 500 milligrams two times a day Day 3: 1000 milligrams in morning, 500 milligrams in evening Day 4 onwards: 1000 milligrams two times a day based on individual tolerance Oral Esomeprazole schedule: 40 milligrams Oral Esomeprazole daily until delivery which can be tapered down to 20 milligrams daily based on individual tolerance.

Metformin and Esomeprazole

Esomeprazole DRUG

40 milligrams Oral Esomeprazole daily until delivery which can be tapered down to 20 milligrams daily based on individual tolerance.

Metformin and Esomeprazole

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women 18 years or older
• Women diagnosed with preeclampsia or preeclampsia with severe features or superimposed preeclampsia with chronic hypertension
• Candidates for expectant management and had no clinical indication for immediate delivery

You may not qualify if:

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

Sponsors & Collaborators

• Christiana Care Health Services: lead

Study Sites (1)

Christianacare Health System

Newark, Delaware, 19718, United States

Location

Related Publications (3)

• Cluver CA, Hiscock R, Decloedt EH, Hall DR, Schell S, Mol BW, Brownfoot F, Kaitu'u-Lino TJ, Walker SP, Tong S. Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial. BMJ. 2021 Sep 22;374:n2103. doi: 10.1136/bmj.n2103.

  PMID: 34551918 BACKGROUND

• Kaitu'u-Lino TJ, Brownfoot FC, Beard S, Cannon P, Hastie R, Nguyen TV, Binder NK, Tong S, Hannan NJ. Combining metformin and esomeprazole is additive in reducing sFlt-1 secretion and decreasing endothelial dysfunction - implications for treating preeclampsia. PLoS One. 2018 Feb 21;13(2):e0188845. doi: 10.1371/journal.pone.0188845. eCollection 2018.

  PMID: 29466360 BACKGROUND

• Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008 May 8;358(19):2003-15. doi: 10.1056/NEJMoa0707193.

  PMID: 18463376 BACKGROUND

MeSH Terms

Conditions

Pre-Eclampsia; Premature Birth

Interventions

Metformin; Esomeprazole

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Obstetric Labor, Premature; Obstetric Labor Complications

Intervention Hierarchy (Ancestors)

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

Study Officials

• Derek Bowden, MA,CIP,CHRC

  ChristianaCare Institutional Review Board

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident Physician

Model Details: There are two groups: experimental and control. The control group receives expectant management. The experimental group receives expectant management and medication treatment.

Study Record Dates

• First Submitted: March 30, 2024
• First Posted: April 11, 2024
• Study Start: February 11, 2021
• Primary Completion: May 8, 2025
• Study Completion: May 8, 2025
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)