Clinical trial NCT05232994: Metformin and Esomeprazole For Preterm Pre-eclampsia
Official title: Use of Combination Metformin and Esomeprazole in Preterm Pre- Eclampsia: Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Preeclampsia Severe
Preeclampsia Second Trimester
Preterm Birth Complication
Lead sponsor: Christiana Care Health Services
Sponsor class: OTHER
First posted: 2022-02-10
Enrollment: 38
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: mean plasma difference in sFlt-1 from randomization to day 7
timeFrame: from randomization to day 7
Secondary outcomes:
measure: Mean plasma difference in vascular endothelial growth factor (VEGF)
timeFrame: from randomization to day 7
measure: Mean plasma difference in placental growth factor (PlGF) levels
timeFrame: from randomization to day 7
measure: Mean plasma difference in soluble endoglin (sEng)
timeFrame: from randomization to day 7
measure: Maternal death
timeFrame: At time of delivery
measure: Mean highest blood pressure during expectant management mmHg
timeFrame: At time of delivery
measure: Number of anti-hypertensive medications at delivery
timeFrame: at time of delivery
measure: 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
timeFrame: at time of delivery
measure: Gestational age at delivery
timeFrame: at time of delivery
measure: Neonatal intensive care unit (nicu) admission
timeFrame: at time of delivery
Other outcomes:
Locations:
city: Newark
country: United States
facility: Christiana Care Health Systems
state: Delaware
Study officials:
affiliation: ChristianaCare
name: Matthew Hoffman, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: