Metformin + Esomeprazole for Pre-eclampsia

Overseen By Marwan Ma'ayeh, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Christiana Care Health Services

Must not be taking: Metformin, Esomeprazole, Glyburide, others

Disqualifiers: Diabetes, Metabolic acidosis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Until delivery

38 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking metformin or certain drugs that interact with it, like glyburide or furosemide.

What evidence supports the effectiveness of the drug combination of Metformin and Esomeprazole for treating pre-eclampsia?

Research shows that both Metformin and Esomeprazole can reduce harmful substances from the placenta that contribute to pre-eclampsia, and together they may help improve blood vessel function, making them promising candidates for treating this condition. ^{1 2 3 4 5}

Is the combination of Metformin and Esomeprazole safe for treating pre-eclampsia?

Metformin is considered safe during pregnancy and is commonly used to treat gestational diabetes, while Esomeprazole is a proton pump inhibitor used for gastric reflux and has been studied for its potential in treating pre-eclampsia. Existing clinical data suggest that Metformin is safe in human pregnancies, and Esomeprazole has been used during pregnancy, although its use is associated with a slightly increased risk of preeclampsia. However, more research is needed to fully understand the safety of combining these drugs for pre-eclampsia treatment. ^{1 2 4 6 7}

How is the drug combination of Metformin and Esomeprazole unique for treating pre-eclampsia?

The combination of Metformin and Esomeprazole is unique for treating pre-eclampsia because it targets the reduction of harmful factors like sFlt-1 and soluble endoglin, which are linked to high blood pressure and organ damage in pregnancy. This combination also helps improve blood vessel function, potentially allowing pregnancies to continue safely to a later stage, unlike the current standard where delivery is the only definitive treatment. ^{1 2 3 4 8}

What is the purpose of this trial?

This trial tested a slow-releasing form of the medication metformin on pregnant women with early pre-eclampsia. The goal was to see if it could help prolong their pregnancies. The treatment works by lowering harmful substances that can cause blood vessel problems. Results showed that metformin could indeed help extend pregnancy duration in these women. Metformin has been studied for its potential to reduce the risk of pre-eclampsia and has shown promise in both preclinical and clinical studies.

Research Team

Matthew Hoffman, MD

Principal Investigator

ChristianaCare

Eligibility Criteria

This trial is for women over 18 with preterm pre-eclampsia between 24 and almost 32 weeks of pregnancy, carrying a single baby without major anomalies. It's not for those likely to deliver within 48 hours, with immediate delivery needs due to maternal or fetal issues, diabetes on metformin therapy, contraindications to the drugs being tested, certain kidney function levels, using interacting medications, multiple pregnancies, metabolic acidosis or allergies to the drugs.

Inclusion Criteria

I am a woman with worsening high blood pressure during pregnancy.

I am a woman aged 18 or older.

I am advised to wait for natural labor without any medical reason for immediate delivery.

Exclusion Criteria

Maternal or fetal compromise that necessitated immediate delivery

Hypersensitivity to metformin or esomeprazole

Metabolic acidosis

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination metformin and esomeprazole until delivery

Until delivery

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Esomeprazole
• Metformin
• Placebo

Trial Overview The study tests if Esomeprazole (20mg) combined with extended release Metformin can help prolong pregnancy in women with preterm pre-eclampsia. This follows evidence that both drugs may reduce harmful substances from the placenta and improve blood vessel function.

Participant Groups

Group I: combination metformin and esomeprazole Experimental Treatment 1 Intervention

Combination 2 g of oral extended release metformin, in divided doses and Esomeprazole 20mg daily until delivery.

Group II: expectant management Active Control 1 Intervention

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

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Christiana Care Health Services

Lead Sponsor

Trials

118

Recruited

204,000+

Findings from Research

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. Ireland pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

Combining metformin and esomeprazole is additive in reducing sFlt-1 secretion and decreasing endothelial dysfunction - implications for treating preeclampsia. [2018]

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

The glucagon-like peptide 1 receptor agonist liraglutide attenuates placental ischemia-induced hypertension. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Current Researches, Rationale, Plausibility, and Evidence Gaps on Metformin for the Management of Hypertensive Disorders of Pregnancy. [2021]

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

Proton Pump Inhibitors and Preeclampsia Risk Among 157 720 Women. [2019]

8. 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]