Preeclampsia Severe, Preeclampsia Second Trimester, Preterm Birth Complication
Conditions
Brief summary
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.
Interventions
Combination 2 g of oral extended release metformin, Esomeprazole 20mg daily until delivery.
Sponsors
Christiana Care Health Services
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| mean plasma difference in sFlt-1 from randomization to day 7 | from randomization to day 7 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Mean plasma difference in vascular endothelial growth factor (VEGF) | from randomization to day 7 |
| 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 |
| Number of anti-hypertensive medications at delivery | at time of delivery |
Countries
United States
Contacts
Primary ContactMarwan Ma'ayeh, MD
Backup ContactKendall M Bielak, MD
Outcome results
None listed