Metformin + Esomeprazole for Preterm Pre-eclampsia

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Christiana Care Health Services

Must not be taking: Metformin, Esomeprazole

Disqualifiers: Diabetes, Reflux disease, Metabolic acidosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3-4 months

4 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are currently taking metformin or esomeprazole, or if you use drugs that might interact with metformin like glyburide, furosemide, or cationic drugs.

What evidence supports the effectiveness of esomeprazole for treating preterm pre-eclampsia?

Research shows that esomeprazole, a drug commonly used for acid reflux, can reduce factors associated with pre-eclampsia, such as sFLT-1 and endothelial dysfunction, and enhance blood vessel relaxation, making it a promising candidate for treating pre-eclampsia. ^{1 2 3 4 5}

Is the combination of Metformin and Esomeprazole generally safe for humans?

Esomeprazole, a medication used to treat acid-related disorders, is generally considered safe with common side effects like headache and abdominal symptoms. It has been shown to be at least as safe as other similar medications. However, specific safety data for the combination of Metformin and Esomeprazole is not provided in the available research. ^{1 5 6 7 8}

How does the drug Metformin + Esomeprazole differ from other treatments for preterm pre-eclampsia?

The combination of Metformin and Esomeprazole is unique because Metformin, commonly used for gestational diabetes, has shown potential in treating pre-eclampsia by allowing pregnancies to continue safely, while Esomeprazole, a proton pump inhibitor, may help reduce factors associated with pre-eclampsia, such as endothelial dysfunction and anti-angiogenic factors, making this combination a novel approach compared to the standard treatment of delivery. ^{2 3 9 10 11}

What is the purpose of this trial?

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.

Research Team

Derek Bowden, MA,CIP,CHRC

Principal Investigator

ChristianaCare Institutional Review Board

Eligibility Criteria

This trial is for pregnant individuals diagnosed with preterm preeclampsia, a condition characterized by high blood pressure and signs of damage to another organ system. The study aims to include those who need new treatment options and are willing to try Metformin or Esomeprazole.

Inclusion Criteria

I am a woman aged 18 or older.

I have been diagnosed with preeclampsia during my pregnancy.

My condition allows for waiting before delivery without immediate medical intervention.

Exclusion Criteria

Hypersensitivity to metformin or esomeprazole

Baseline creatinine >124 μmol/L

Maternal or fetal compromise that necessitated immediate delivery

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin and esomeprazole for preterm preeclampsia management

3-4 months

Regular visits throughout pregnancy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Esomeprazole
• Metformin

Trial Overview The trial is testing the effectiveness of two medications, Metformin and Esomeprazole, in treating preterm preeclampsia. It also seeks to identify serum markers that could help diagnose this condition more accurately.

Participant Groups

Group I: Metformin and Esomeprazole Experimental Treatment 2 Interventions

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

Group II: No Intervention Active Control 1 Intervention

Patients diagnosed with preterm preeclampsia receive expectant management only.

Esomeprazole is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Nexium for:

• Gastroesophageal reflux disease (GERD)
• Stomach ulcers
• Duodenal ulcers
• Zollinger-Ellison Syndrome

Approved in United States as Nexium for:

• Gastroesophageal reflux disease (GERD)
• Stomach ulcers
• Duodenal ulcers
• Zollinger-Ellison Syndrome
• Pathological hypersecretory conditions

Approved in Canada as Nexium for:

• Gastroesophageal reflux disease (GERD)
• Stomach ulcers
• Duodenal ulcers
• Zollinger-Ellison Syndrome

Approved in Japan as Nexium for:

• Gastroesophageal reflux disease (GERD)
• Stomach ulcers
• Duodenal ulcers

Approved in China as Nexium for:

• Gastroesophageal reflux disease (GERD)
• Stomach ulcers
• Duodenal ulcers

Approved in Switzerland as Nexium for:

• Gastroesophageal reflux disease (GERD)
• Stomach ulcers
• Duodenal ulcers
• Zollinger-Ellison Syndrome

Who Is Running the Clinical Trial?

Christiana Care Health Services

Lead Sponsor

Trials

118

Recruited

204,000+

Findings from Research

Esomeprazole sodium remains chemically and physically stable for at least 2 days at room temperature and 5 days when refrigerated, making it suitable for short-term infusion use.

The study found no significant loss of drug content (less than 7%) in esomeprazole samples across various infusion solutions, indicating its reliability for treating gastroesophageal reflux disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical and chemical stability of esomeprazole sodium solutions. Kupiec, TC., Aloumanis, V., Ben, M., et al.[2022]

In a study of 47 mechanically ventilated patients at high risk for stress ulcers, intravenous esomeprazole effectively maintained gastric acidity above pH 5 and prevented bleeding of the gastric mucosa, demonstrating its safety and efficacy as a preventive treatment.

No instances of gastric mucosal bleeding were observed, and the study suggests that esomeprazole could be a reliable option for preventing stress ulcers in ICU patients, although further comparative studies with other treatments are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficiency and safety of the intravenous application of esomeprazole (nexium - Astra Zeneca) in high risk patients subjected to mechanic ventilation]. Stefanov, Ch., Batashki, I., Dimitrov, D., et al.[2018]

Esomeprazole, as a single isomer of omeprazole, shows improved pharmacokinetics and pharmacodynamics, leading to better acid control in the stomach compared to other proton pump inhibitors.

Clinical trials have demonstrated that esomeprazole is effective in treating gastroesophageal reflux disease and in healing ulcers associated with nonsteroidal anti-inflammatory drugs, highlighting its clinical significance in managing acid-related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esomeprazole: potent acid suppression in the treatment of acid-related disorders. Morgner-Miehlke, A., Petersen, K., Miehlke, S., et al.[2010]

The PI2 Trial is a phase II clinical study involving 150 women with preterm pre-eclampsia, testing the efficacy of extended-release metformin compared to a placebo, with the primary goal of delaying delivery by at least 5 days.

Metformin is already known to be safe during pregnancy and may provide a new therapeutic option to manage preterm pre-eclampsia, potentially improving outcomes for both mothers and their babies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double blind, randomised, placebo-controlled trial to evaluate the efficacy of metformin to treat preterm pre-eclampsia (PI2 Trial): study protocol. Cluver, C., Walker, SP., Mol, BW., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Physical and chemical stability of esomeprazole sodium solutions. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Magnesium sulfate versus esomeprazole impact on the neonates of preeclamptic rats. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Esomeprazole: a clinical review. [2019]

6. Bulgaria pubmed.ncbi.nlm.nih.gov

[Efficiency and safety of the intravenous application of esomeprazole (nexium - Astra Zeneca) in high risk patients subjected to mechanic ventilation]. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Structural characterization of the optical isomers esomeprazole and omeprazole using the JADER and FAERS databases. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Esomeprazole: potent acid suppression in the treatment of acid-related disorders. [2010]

9. England pubmed.ncbi.nlm.nih.gov

A double blind, randomised, placebo-controlled trial to evaluate the efficacy of metformin to treat preterm pre-eclampsia (PI2 Trial): study protocol. [2023]

10. Denmark pubmed.ncbi.nlm.nih.gov

Clinical experiences and a review of chlormethiazole in the management of pre-eclampsia and eclampsia. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of esomeprazole in patients with preterm preeclampsia. [2022]