PI4 - A Trial Assessing Metformin to Prolong Gestation in Preterm Preeclampsia
Preeclampsia Intervention 4 - A Triple Blind Phase III Randomised Controlled Trial Assessing Metformin to Prolong Gestation in Preterm Preeclampsia
Lina Bergman
294 participants
Jan 19, 2024
INTERVENTIONAL
Conditions
Summary
Preterm preeclampsia is a severe condition for both the mother and the fetus. Currently, the only treatment available to stop disease progression is termination/delivery of the fetus and placenta. Therefore, preterm preeclampsia carries the highest rates of neonatal morbidity and mortality due to iatrogenic preterm birth. There is evidence suggesting metformin, a drug commonly used to treat diabetes in and outside pregnancy, may be able to counter the pathophysiology of preeclampsia, raising the possibility that it could be used to treat the condition. This multi centre double blind randomised controlled trial aims to investigate if metformin can prolong gestation, lower neonatal length of stay and increase birthweight in a Swedish setting.
Eligibility
Inclusion Criteria6
- A diagnosis of preeclampsia (defined as hypertension in combination with significant proteinuria (albumin/creatinine ratio \>8 mg/mmol, protein/creatinine ratio\>30 mg/mmol or \>2+ protein on a urinary dipstick) has been made by the attending clinician
- The managing clinicians have made the assessment to proceed with expectant management.
- The subject has given written consent to participate in the study.
- The woman must be 18 years of age or older
- The gestational age is between 22+0 weeks to 33+6 weeks with a viable fetus
- The woman carries a singleton pregnancy
Exclusion Criteria13
- Contraindications to treatment with metformin as outlined in SmPC
- Contraindications for expectant management of preeclampsia such as an immediate indication for delivery according to SFOG guidelines for preeclampsia (https://www.sfog.se/media/338533/pe-riktlinje-230214.pdf).
- Type 1 Diabetes Mellitus
- Current use of metformin
- Known or suspected allergies against metformin
- Reluctance or language difficulties that result in difficulty understanding the meaning of study participation
- Unable to understand the informed consent process
- Previous participation in the study
- Established fetal compromise that necessitates imminent delivery (including planned delivery after 48 hours of corticosteroid treatment). This will be decided by the clinical team before expectant management is offered to the patient.
- Suspicion of a major known fetal anomaly or malformation.
- Renal disease or dysfunction, suggested by a creatinine level greater than or equal to 125 µmol/L or rapidly declining renal function
- Known acute or chronic metabolic acidosis, including diabetic ketoacidosis
- Not suitable for inclusion by the opinion of the investigator
Interventions
Metformin ER, one gram three times daily taken orally. Once the participants have been recruited, they will start by taking one 500 mg tablet three times a day. If well tolerated it will be increased day two to a maximum of two tablets three times a day. Treatment will continue until delivery. If there are side effects that are not tolerable, the dose will be decreased and the participant will remain blinded. Each participant will keep a treatment diary and number of tablets taken will be documented by the participant or hospital staff. The study will not alter or interfere with treatment or care routinely given for preterm preeclampsia.
Placebo, two tablets three times daily taken orally. Once the participants have been recruited, they will start by taking one tablet three times a day. If well tolerated it will be increased day two to a maximum of two tablets three times a day. Treatment will continue until delivery. If there are side effects that are not tolerable, the dose will be decreased and the participant will remain blinded. Each participant will keep a treatment diary and number of tablets taken will be documented by the participant or hospital staff. The study will not alter or interfere with treatment or care routinely given for preterm preeclampsia.
Locations(9)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06033131