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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods to diagnose and treat preterm preeclampsia, a condition in pregnant women marked by high blood pressure and potential organ damage. Researchers are testing two treatments, Metformin and Esomeprazole (commonly used to reduce stomach acid), to determine their effectiveness in managing this condition. The trial also seeks new blood markers that might improve diagnosis. Women diagnosed with preeclampsia who do not require immediate delivery might be suitable candidates for this trial. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, and the research aims to understand how they benefit more patients.

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 is the safety track record for Metformin and Esomeprazole?

Research has shown that combining metformin and esomeprazole is under study for potential benefits in treating preterm pre-eclampsia. Metformin, commonly used to control blood sugar in diabetes, may help extend pregnancy in women with this condition. Esomeprazole, typically used for acid reflux, is added to enhance the treatment's effectiveness.

Previous studies suggest that this combination is safe. Metformin is generally well-tolerated, with mild side effects like nausea. Esomeprazole also has a good safety record, with mild side effects such as headache or stomach pain. Together, these drugs appear safe, with no serious side effects reported in early research.

The trial is in a later stage, providing more safety information than earlier phases. This indicates that the combination has been safe in humans over time. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about combining metformin and esomeprazole for preterm pre-eclampsia because it offers a novel approach compared to traditional treatments like antihypertensives and corticosteroids. Metformin, typically used for diabetes, may help by improving blood vessel function and reducing inflammation, while esomeprazole, a proton pump inhibitor, might have protective effects on vascular health. This combination targets different pathways, potentially offering a more comprehensive management strategy for pre-eclampsia, which is why it's generating interest in the medical community.

What evidence suggests that this trial's treatments could be effective for preterm preeclampsia?

This trial will compare the combination of metformin and esomeprazole with expectant management alone for patients with preterm preeclampsia. Research has shown that using metformin and esomeprazole together might be more effective in treating early preeclampsia than using either drug alone. Studies indicate that this combination can help lower the levels of certain substances released by the placenta, which are involved in preeclampsia. Metformin alone has been associated with a significant decrease in preeclampsia cases. Specifically, one study found a 70% reduction in preeclampsia rates among some high-risk groups using metformin. This suggests that these medications might help manage early preeclampsia more effectively. ^{1 2 3 6 7}

Who Is on the Research Team?

Derek Bowden, MA,CIP,CHRC

Principal Investigator

ChristianaCare Institutional Review Board

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5821305/

Combining metformin and esomeprazole is additive in ... The combination of metformin and esomeprazole may provide a more effective treatment or prevention for preeclampsia compared to either as single ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05232994?term=AREA%5BBasicSearch%5D(%22christiana%20care%22)&rank=9

Metformin and Esomeprazole For Preterm Pre-eclampsia Details for study NCT05232994, | ClinicalTrials.gov.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11575948/

Metformin Use and Preterm Preeclampsia in Pregnant ... In contrast, Syngelaski et al. reported a 70% reduction in preeclampsia (from 11% to 3%) among participants with obesity randomized to ...

4. ctv.veeva.com ctv.veeva.com/study/metformin-and-esomeprazole-for-preterm-pre-eclampsia

Metformin and Esomeprazole For Preterm Pre-eclampsia Combination metformin and esomeprazole has shown promise in the treatment of preeclampsia as both agents reduce placental and endothelial secretion.

5. preeclampsia.org preeclampsia.org/public/frontend/assets/img/gallery/pdf/2021%20Summary.pdf

Metformin to treat Preterm Pre-eclampsia: A randomised, ... The primary outcome was prolongation of pregnancy. ... were observed though gastrointestinal side effects were common among those who took metformin.

6. trial.medpath.com trial.medpath.com/clinical-trial/35fcababb3baf108/use-metformin-esomeprazole-preterm-eclampsia

Metformin and Esomeprazole For Preterm Pre-eclampsia Investigators found that extended release metformin (3g daily) can prolong gestation in women with preterm pre-eclampsia. Combination metformin and esomeprazole ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03717701?cond=%22Eclampsia%22&intr=%22Metformin%22&viewType=Table&rank=3

Metformin and Esomeprazole in Treatment of Early Onset ... Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...