TY - JOUR
T1 - Does metformin prolong pregnancy in preterm pre-eclampsia? A study protocol for a South African, hospital-based double-blind, randomised, placebo-controlled trial
AU - Cluver, Catherine Anne
AU - Bergman, Lina
AU - Imberg, Henrik
AU - Mol, Ben W.
AU - Hall, David
AU - Bekker, Adrie
AU - Gordon, Adrienne
AU - Brownfoot, Fiona
AU - Kaitu’u-Lino, Tu'uhevaha J.
AU - Walker, Susan P.
AU - Tong, Stephen
N1 - Funding Information:
This trial is supported by an investigator-initiated grant from Merck Healthcare KgaA, Darmstadt, Germany (award/grant number N/A). The trial also receives funding supported from the Mercy Health Foundation, the Wallenberg Center for Molecular and Translational Medicine, the Swedish Research Council and the Swedish Society of Medicine (award grant numbers N/A). The National Health and Medical Research Council of Australia provides salary support to BWM, TJK-L, FB and ST. CAC receives salary support from the Mercy Health Foundation and the Swedish Research Council. LB receives salary support from Wallenberg Center for Molecular and Translational Medicine. This is an investigator-initiated trial. The funders will have no role in the collection, analysis, interpretation of data, writing of the article or decision to submit the article for publication.
Publisher Copyright:
© Author(s) (or their employer(s)) 2024.
PY - 2024/6
Y1 - 2024/6
N2 - Introduction Preterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week in pregnant women undergoing expectant management (7.6 days, geometric mean ratio 1.39, 95% CI 0.99 to 1.95; p=0.057). These findings should be confirmed with a larger sample size, and we need to know if such a prolongation improves neonatal outcome. Here, we describe the protocol for such a follow-up trial. Methods The PI 3 trial is a phase III, intention-to-treat, double-blind, placebo-controlled randomised clinical trial to assess if metformin XR can prolong gestation and improve neonatal outcomes in women undergoing expectant management for preterm pre-eclampsia. We will recruit women who are between 26+0 and 31+6 weeks pregnant. Women will be randomised to receive either 3 g metformin XR or an identical placebo in divided daily doses. The primary outcome is prolongation of pregnancy. Secondary outcomes are neonatal birth weight and length of neonatal care admission (an indicator of neonatal health at birth). All other outcomes will be exploratory. We will record tolerability and adverse events. We plan a sample size of 500 participants to be powered for the primary and secondary outcomes. Ethics and dissemination PI 3 has ethical approval (Health Research Ethics Committee 2, Stellenbosch University, Protocol number M21/03/007, Project ID 21639, Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), and is registered with the Pan African Clinical Trial Registry (PACTR202104532026017) and the South African Medicine Control Council (20211211). Data will be presented at international conferences and published in peer-reviewed journals.
AB - Introduction Preterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week in pregnant women undergoing expectant management (7.6 days, geometric mean ratio 1.39, 95% CI 0.99 to 1.95; p=0.057). These findings should be confirmed with a larger sample size, and we need to know if such a prolongation improves neonatal outcome. Here, we describe the protocol for such a follow-up trial. Methods The PI 3 trial is a phase III, intention-to-treat, double-blind, placebo-controlled randomised clinical trial to assess if metformin XR can prolong gestation and improve neonatal outcomes in women undergoing expectant management for preterm pre-eclampsia. We will recruit women who are between 26+0 and 31+6 weeks pregnant. Women will be randomised to receive either 3 g metformin XR or an identical placebo in divided daily doses. The primary outcome is prolongation of pregnancy. Secondary outcomes are neonatal birth weight and length of neonatal care admission (an indicator of neonatal health at birth). All other outcomes will be exploratory. We will record tolerability and adverse events. We plan a sample size of 500 participants to be powered for the primary and secondary outcomes. Ethics and dissemination PI 3 has ethical approval (Health Research Ethics Committee 2, Stellenbosch University, Protocol number M21/03/007, Project ID 21639, Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), and is registered with the Pan African Clinical Trial Registry (PACTR202104532026017) and the South African Medicine Control Council (20211211). Data will be presented at international conferences and published in peer-reviewed journals.
KW - Clinical Trial
KW - Fetal medicine
KW - Maternal medicine
KW - Neonatology
KW - Pregnancy
KW - Randomized Controlled Trial
UR - http://www.scopus.com/inward/record.url?scp=85196603307&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2023-082880
DO - 10.1136/bmjopen-2023-082880
M3 - Article
C2 - 38890136
AN - SCOPUS:85196603307
SN - 2044-6055
VL - 14
JO - BMJ Open
JF - BMJ Open
IS - 6
M1 - e082880
ER -