Metformin and Esomeprazole For Preterm Pre-eclampsia

Study Overview
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Brief Summary
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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.

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

Conditions
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Preeclampsia Severe, Preeclampsia Second Trimester, Preterm Birth Complication

Intervention / Treatment
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* Drug: Esomeprazole 20mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: combination metformin and esomeprazole<br>Combination 2 g of oral extended release metformin, in divided doses and Esomeprazole 20mg daily until delivery. | Drug: Esomeprazole 20mg<br>* Combination 2 g of oral extended release metformin, Esomeprazole 20mg daily until delivery.<br>* Other names: Metformin;|
| No Intervention: expectant management<br> | |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Gestational age at delivery |  | at time of delivery | 
| Neonatal intensive care unit (nicu) admission |  | at time of delivery |