Metformin in Women With Type 2 Diabetes in Pregnancy Trial (MiTy)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Metformin in Women With Type 2 Diabetes in Pregnancy Trial|
- A composite of: pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, and NICU admission > 24 hours. [ Time Frame: conception to 28 days after birth ]
- Large for gestational age (LGA) infants [ Time Frame: Up to 24 hours after birth ]Defined as greater than the 90th percentile for weight, based on the National canadian fetal growth standards for singleton boys and girls.
- Pregnancy loss [ Time Frame: Up to 40 weeks gestation ]Spontaneous abortion defined as death of a fetus at <20 weeks gestation; Stillbirth defined as death of a fetus with a birth weight ≥ 500g or at ≥ 20 wks gestational age regardless of birth weight; Neonatal death defined as death of a live born infant within the first 28 days of life or prior to hospital discharge, whichever is later.
- Preterm birth [ Time Frame: Up to 37 weeks gestation ]Birth < 37 weeks gestation
- Respiratory distress [ Time Frame: within 72 hours after birth ]Given surfactant via an endotracheal tube and/or requiring assisted positive pressure ventilation within 72 hours after birth.
- Neonatal hypoglycemia [ Time Frame: NICU admission >24 hours ]A plasma glucose <2.6 mmol/L on one or more occasions, starting at 30-60 minutes after birth, and necessitating intravenous dextrose within the first 48 hours of life.
- NICU admission >24 hours [ Time Frame: NICU admission >24 hours ]Admission to a neonatal intensive or special care unit for > 24 hours during the initial hospitalization after birth
- Cord blood gases pH <7.0 [ Time Frame: Within 4 hours of birth ]
- Hyperinsulinemia as measured by elevated cord blood C-peptide [ Time Frame: Within 4 hours of birth ]A cord serum C-peptide value > 1.7 ug/L (which is >90th percentile of values for the total cohort of participants in the HAPO trial) will be defined as hyperinsulinemia.
- Maternal glycemic control as measured by HbA1c and capillary glucose measurements. [ Time Frame: Up to 40 weeks gestation ]Gestational age at testing will be recorded. All downloaded glucose results will be transmitted on a regular basis to a central site for future analysis. Monthly correlations will be done with the laboratory during routine monthly blood draws.
- Maternal hypoglycemia [ Time Frame: Up to 40 weeks gestation ]Maternal hypoglycemia defined as mild (<3.6, symptomatic and asymptomatic or requiring treatment), or severe (loss of consciousness or confusion requiring assistance) will be documented at each visit.
- Maternal weight gain [ Time Frame: Up to 40 weeks gestation ]The first and last weight will be obtained at the first and last visit in pregnancy, whether they be done by the endocrinologist, family physician or obstetrician.
- Maternal insulin doses [ Time Frame: Up to 40 weeks gestation ]Maternal insulin doses (overall amount and number of patients that are taking 'high' insulin doses defined as 2 Units/kg or more per day)
- Pre-eclampsia, and/or gestational hypertension [ Time Frame: Up to 40 weeks gestation ]
Gestational hypertension: New onset of hypertension in pregnancy ≥ 20 weeks gestation in a woman with previously normal blood pressure, defined as diastolic blood pressure of ≥ 90 mmHg, taken on 2 occasions or placed on antihypertensive medication and without proteinuria.
Pre-eclampsia: please refer to protocol for definition
- Sepsis [ Time Frame: Up to 28 days after birth ]A positive blood and/or cerebral spinal fluid culture during the neonatal hospital stay.
- Hyperbilirubinemia [ Time Frame: First 7 days of life ]Significant jaundice was present based on bilirubin levels requiring treatment with phototherapy> 6 continuous hours, or an exchange transfusion, or receiving intravenous gamma globulin, or requiring readmission into hospital during the first 7 days of life.
- Number of hospitalizations [ Time Frame: Up to 40 weeks gestation ]Number of hospitalizations prior to admission for delivery and the duration of hospital stays for the mother prior to admission for delivery and associated with delivery.
- Rate of caesarean-section [ Time Frame: Up to 40 weeks gestation ]
- Duration of hospital stay for infant. [ Time Frame: Up to 28 days after birth ]Duration of hospital stay for infant associated with his/her birth until the first discharge home
- Fetal fat mass [ Time Frame: Up to 7 days after birth ]Fetal fat mass compared with women treated with insulin plus placebo
- Birth Injury [ Time Frame: Up to 7 days after birth ]Defined as any of the following: spinal cord injury, basal skull fracture or depressed skull fracture, clavicular fracture, long bone fracture, subdural or intracerebral hemorrhage or any kind
- Shoulder dystocia [ Time Frame: At delivery ]Documentation of any shoulder dystocia in the delivery records, plus 3 or more of the following: McRoberts maneuver, suprapubic maneuver, episiotomy, delivery of the posterior arm, Woods maneuver, Rubins maneuver, All fours Gaskins maneuver, intentional fracture of the clavicle, and/or Zavenelli maneuver.
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||June 2018|
|Estimated Primary Completion Date:||June 2018 (Final data collection date for primary outcome measure)|
|Active Comparator: Metformin||
500 mg daily OD from randomisation for 2 weeks, then 1000mg BID throughout the duration of pregnancy
|Placebo Comparator: Sugar pill||
Drug: Placebo Comparator
Please refer to this study by its ClinicalTrials.gov identifier: NCT01353391
|Contact: Siobhan Tobin, Hon.B.Sc.||firstname.lastname@example.org|
|Contact: Johanna Sanchez, MIPHemail@example.com|
|The Centre for Mother, Infant, and Child Research, Sunnybrook Research Institute||Recruiting|
|Toronto, Ontario, Canada, M4N 3M5|
|Contact: Siobhan Tobin, Hon.B.Sc. 416-480-5631 firstname.lastname@example.org|
|Contact: Trinh Hoac, MIPH 416-480-6100 ext 87535 email@example.com|
|Sub-Investigator: Shital Gandhi, MD|
|Principal Investigator:||Denice Feig, MD||Mount Sinai Hospital, New York|