Preeclampsia Intervention Netherlands
- Conditions
- Pre-Eclampsia Onset Less Than 37 WeeksPre-EclampsiaHELLPPre-Eclampsia; Complicating PregnancyPre-Eclampsia as Antepartum ConditionPre-eclampsia or Eclampsia With Pre-existing HypertensionPre-Eclampsia; Affecting FetusHELLP Syndrome Complicating PregnancyHELLP Syndrome
- Interventions
- Drug: Placebo
- Registration Number
- NCT06452498
- Lead Sponsor
- Amsterdam UMC
- Brief Summary
The goal of this study is to find out if pregnant individuals with preterm preeclampsia (PE) who are treated with metformin can stay pregnant for longer, and if this is safe(r) for the mother and child. Preterm PE affects about 1 in 100 pregnant individuals in the Netherlands. Signs of preterm PE can be high blood pressure and protein in the urine in the second half of pregnancy (but before 32-34 weeks of pregnancy). Other symptoms can develop, such as problems with blood clotting and how well the blood cells, liver, lungs, and brain work. The disease can lead to serious complications for both the mother and child. The only way to cure preterm PE is to make sure the child is born, and many times, children have to be delivered (very) early (before 37 weeks). Children born (very) early can suffer from infections, breathing difficulties, and problems in their development.
Metformin is a medicine used to treat high blood sugar during and outside of pregnancy. In a previous study in South Africa, women with preterm PE that used metformin were able to safely remain pregnant for an extra week. Similarly, the main goal of the Preeclampsia Intervention NetherLands (PI-NL) study is to see if patients with preterm PE in the Netherlands that use metformin can remain pregnant for a longer time than patients taking a placebo. A placebo is a look-a-like capsule that contains no active ingredients. Researchers, the treating medical team, and participants will not know which participant gets which treatment. In addition, all participants will receive the standard care that all preterm PE patients get.
- Detailed Description
Preterm preeclampsia (PE) is a severe hypertensive disorder of pregnancy and a major cause of maternal and perinatal morbidity and mortality. Currently, the only treatment to halt disease progression is delivery of the dysfunctional placenta and thereby the child. This often happens prematurely. Being able to safely (for mother and child) extend pregnancy, even by a few days, is expected to reduce the short- and long-term risks associated with (severe) prematurity. Preclinical and recent clinical evidence presents metformin, a drug commonly used to treat diabetes in and outside of pregnancy, as a promising treatment candidate for preterm PE. Metformin might reduce inflammation, oxidative stress, and anti-angiogenesis, and improve endothelial function. In a recent South African trial, use of metformin was associated with a safe median 7.6 day prolongation of pregnancy in women with preterm PE, compared to placebo. There was a nonsignificant increase in the neonatal birthweight and a decrease in the length of stay in any neonatal nursery. Metformin did not lead to any serious adverse events.
The goal of this multicenter, triple-blind, randomized placebo-controlled trial is to investigate whether metformin can safely prolong gestation in patients with preterm PE in the Dutch population. Secondary outcomes include composite adverse maternal, fetal, and neonatal outcomes. Cost-effectiveness of the treatment will be evaluated.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 180
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo, divided by three daily doses (3 times 2 capsules; following a step-up schedule) from randomization till delivery, aside from usual preterm preeclampsia care. Metformin Metformin Hydrochloride Metformin 3000 mg divided by three daily doses (3 times 2 capsules of 500 mg; following a step-up schedule) from randomization till delivery, aside from usual preterm preeclampsia care.
- Primary Outcome Measures
Name Time Method Number of days between randomization and delivery Time between randomization and delivery (up to 37 weeks of gestation) Prolongation of gestation
- Secondary Outcome Measures
Name Time Method Number of participants reaching a composite maternal adverse outcome Randomization till 90 days postpartum (unless otherwise specified) Combined endpoint of maternal death (during pregnancy or within 42 days postpartum), eclampsia, pulmonary edema, severe renal impairment, cerebrovascular accident, placental abruption, and/or liver hematoma or rupture.
Number of participants reaching a composite fetal adverse outcome Randomization till delivery (up to 37 weeks of gestation) Combined endpoint of intrauterine fetal demise, suboptimal fetal condition based on CTG, and fetal growth restriction.
Number of participants reaching a composite neonatal adverse outcome Birth till 90 days after birth (unless otherwise specified) Combined endpoint of neonatal death (within 28 days after birth), grade 3 or 4 intraventricular hemorrhage, retinopathy of prematurity requiring treatment, necrotizing enterocolitis (grade II or higher), bronchopulmonary dysplasia, neonatal sepsis, and cystic periventricular leukomalacia (grade II or higher)