Clinical trial NCT02980276: RCT Metformin for Reduction of Gestational Diabetes Mellitus Effects
Official title: A Randomised Placebo Controlled Trial of the Effectiveness of Early MEtformin in Addition to Usual Care in the Reduction of Gestational Diabetes Mellitus Effects (EMERGE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gestational Diabetes
Keywords: Gestational Diabetes
Diabetes
Pregnancy
Lead sponsor: National University of Ireland, Galway, Ireland
Sponsor class: OTHER
Collaborators: name: Health Research Board, Ireland
name: HRB Clinical Research Facility Galway
name: University College Hospital Galway
name: Portiuncula University Hospital
name: University Hospital of Limerick
name: University Maternity Hospital Limerick
name: Clinical Research Support Unit, University of Limerick
First posted: 2016-12-02
Enrollment: 535
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The overall objective of the EMERGE trial is to determine whether metformin + usual care, compared to placebo + usual care (introduced at the time of initial diagnosis of GDM), reduces a) the need for insulin use, or hyperglycemia (primary outcome measure); b) excessive maternal weight gain; c) maternal and neonatal morbidities and, d) cost of treatment for women with Gestational Diabetes Mellitus.


Eligibility criteria: Inclusion Criteria:

1. Willing and able to provide written informed consent
2. Participants aged 18-50
3. Pregnancy gestation up to 28 weeks (+ 6 days) confirmed by positive pregnancy test
4. Singleton pregnancy as determined by scan
5. Positive diagnosis of Gestational Diabetes Mellitus on a Oral Glucose Tolerance Test (OGTT) according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria if any one of the following are achieved: i) Fasting glucose \>/= 5.1mmol/l and \<7mmol/l, or ii) 1 hour post glucose load of \>/=10mmol/l, or iii) 2 hour post glucose load of \>/=8.5 mmol/l and \<11.1mmo/l
6. Resident in the locality and intending to deliver within the trial site

Exclusion Criteria:

1. Participants who have an established diagnosis of diabetes (Type 1, Type 2, Monogenic or secondary)
2. Participants with a fasting glucose \> 7mmol/l or a 2h value \> 11.1 mmol/l
3. Multiple pregnancies (twins, triplets etc.) as determined by scan
4. Known intolerance to metformin
5. Known contraindication to the use of metformin which include: i) renal insufficiency (defined as serum creatinine of greater than 130 µmol/L or creatinine clearance \<60 ml/min), ii) moderate to severe liver dysfunction (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) greater than 3 times the upper limit of normal, iii) shock or sepsis, and iv) previous hypersensitivity to metformin
6. Major congenital malformations or an abnormally deemed unsuitable for metformin by the site PI or attending consultant
7. Known small for gestational age (Small for gestational age (SGA) refers to foetal growth less than the 10th percentile (RCOG, 2014), or if foetal growth is deemed unsatisfactory by the treating obstetrician)
8. Known gestational hypertension or pre-eclampsia or ruptured membranes
9. Participants who have a history of drug or alcohol use that, in the opinion of the investigator, would interfere with adherence to study requirements
10. Participants with significant gastrointestinal problems such as severe vomiting, Crohn's disease or colitis which will inadvertently affect absorption of the study drug
11. Participants with congestive heart failure or history of congestive heart failure
12. Participants with serious mental illness which would affect adherence to study medication or compliance with study protocol in the opinion of the investigator
13. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

Primary outcomes:
measure: Primary Composite Outcome
timeFrame: Enrolment through delivery, an average of 16 weeks.
measure: Insulation of Insulin
timeFrame: Enrolment through delivery, an average of 16 weeks.
Secondary outcomes:
measure: Time to Insulin Initiation
timeFrame: Time to Insulin Initiation, from date of randomization until the date of delivery, an average of 16 weeks..
measure: Insulin Initiated
timeFrame: Enrolment through delivery, an average of 16 weeks.
measure: Fasting Hyperglycemia
timeFrame: Measured at 32 and 38 weeks' gestation.
measure: Insulin Dose Required
timeFrame: Enrolment through delivery, an average of 16 weeks.
measure: Gestational Weight Gain
timeFrame: Enrolment through delivery, an average of 16 weeks.
measure: Postpartum Impaired Fasting Glucose
timeFrame: 12 weeks post-partum
measure: Postpartum Impaired Glucose Tolerance
timeFrame: 12 weeks postpartum
measure: Postpartum Metabolic Syndrome
timeFrame: 12 weeks postpartum
measure: Gestational Age at Delivery
timeFrame: At delivery, an average of 16 weeks after enrolment
measure: Mode of Delivery - Cesarian Delivery
timeFrame: At delivery, an average of 16 weeks after enrolment
measure: Mode of Delivery - Emergency Cesarian Section
timeFrame: At delivery, an average of 16 weeks after randomization.
measure: Mode of Delivery - Induced
timeFrame: At time of labor, an average of 16 weeks after enrolment.
measure: Maternal Morbidity - Pregnancy-induced Hypertension
timeFrame: From enrolment through 6 weeks postpartum, an average of 22 weeks.
measure: Maternal Morbidity - Pre-eclampsia
timeFrame: Enrolment through 6 weeks postpartum, an average of 22 weeks.
measure: Maternal Morbidity - Antepartum Hemorrhage
timeFrame: From enrolment through delivery, an average of 16 weeks.
measure: Maternal Morbidity - Postpartum Hemorrhage
timeFrame: From delivery through 6 weeks postpartum.
measure: Birthweight
timeFrame: At birth
measure: Neonatal Head Circumference
timeFrame: At birth
measure: Neonatal Height
timeFrame: At birth
measure: Neonatal Abdominal Circumference
timeFrame: At birth
measure: Neonatal Ponderal Index
timeFrame: At birth
measure: Birth Weight >4000g
timeFrame: At birth
measure: Birth Weight >90th Percentile
timeFrame: At birth
measure: Birth Weight <2500g
timeFrame: At birth
measure: Birth Weight <10th Percentile
timeFrame: At birth
measure: Neonatal Morbidity - Need for NICU Care
timeFrame: From birth until 6 weeks of life.
measure: Neonatal Morbidity - Preterm Birth
timeFrame: At birth
measure: Neonatal Morbidity - Respiratory Distress Syndrome Requiring Respiratory Support
timeFrame: From birth until 6 weeks of life.
measure: Neonatal Morbidity - Jaundice Requiring Phototherapy
timeFrame: From birth until 6 weeks of life.
measure: Neonatal Morbidity - Major Congenital Anomalies
timeFrame: From birth until 6 weeks of life.
measure: Neonatal Morbidity - Apgar Score <7 at 5 Minutes
timeFrame: At 5 minutes after birth
measure: Neonatal Morbidity - Neonatal Hypoglycemia
timeFrame: First hour of life.
Other outcomes:
Locations:
city: Ballinasloe
country: Ireland
facility: Portiuncula University Hospital
state: Galway
city: Galway
country: Ireland
facility: University Hospital Galway
Study officials:
affiliation: National University of Ireland, Galway, Ireland
name: Prof. Fidelma Dunne
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dunne F, Newman C, Devane D, Smyth A, Alvarez-Iglesias A, Gillespie P, Browne M, O'Donnell M. A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol. Trials. 2022 Sep 21;23(1):795. doi: 10.1186/s13063-022-06694-y.