Gestational Diabetes Mellitus Clinical Trial
— DECIDEOfficial title:
DECIDE: A Comparative Effectiveness Trial of Oral Metformin Versus Injectable Insulin for the Treatment of Gestational Diabetes
This is a non-inferiority patient-centered and pragmatic comparative-effectiveness pregnancy randomized controlled trial (RCT) with postpartum maternal and child follow-up through 2 years of 1,572 individuals with gestational diabetes mellitus (GDM) randomized to oral metformin versus injectable insulin. This study will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. A total of 1,572 pregnant individuals with GDM who need pharmacotherapy will be recruited at 20 U.S. sites using consistent treatment criteria to metformin versus insulin. Participants and their children will be followed through delivery to two years postpartum.
Status | Not yet recruiting |
Enrollment | 1572 |
Est. completion date | December 2030 |
Est. primary completion date | December 2029 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Singleton gestation. Twin reduction to singleton, either spontaneously or therapeutically, is eligible if it occurred before 14 weeks gestational age. - Age 18 years or older - Gestational age at randomization between 20 0/7 - 31 6/7 weeks based on project gestational age. - GDM diagnosis between 20 0/7 - 31 6/7 weeks based on project gestational age. - Requires medication for glucose control defined as = 30% elevated glucose values (either fasting or postprandial or both) in the week prior to randomization per determination of the provider or documented in the medical record. - Patient willingness and ability to attend 2-year follow-up visit. Exclusion criteria: - Renal disease (serum creatinine >1.3 mg/dL) due to the potential impact of metformin on renal function. - Major structural malformation of the fetus. - Known fetal aneuploidy based on invasive testing or positive for aneuploidy on cell-free fetal DNA screening. - Contraindication to metformin or insulin, including: history of lactic acidosis, intractable nausea and vomiting, prior documented allergy and/or anaphylaxis. - Pregestational diabetes documented in the medical record, GDM diagnosis <20 weeks, or prior A1c>6.5% - Fasting hyperglycemia >115 mg/dl for = 50% of fasting glucose values in the past week (due to the high risk of metformin failure with fasting hyperglycemia). - Enrolled in a trial that influences primary study outcomes (composite neonatal outcome at delivery or childhood body mass index at 2 years). - Prenatal care or delivery planned at a location where access to the complete electronic medical record will not be available to research staff. - Language barrier (appropriate translation resources unavailable at the site) - Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, may be included. |
Country | Name | City | State |
---|---|---|---|
United States | University of New Mexico | Albuquerque | New Mexico |
United States | University of Texas Austin | Austin | Texas |
United States | Beth Israel Deaconess Medical Center | Boston | Massachusetts |
United States | Massachusetts General Hospital | Boston | Massachusetts |
United States | Tufts University | Boston | Massachusetts |
United States | University of North Carolina Chapel Hill | Chapel Hill | North Carolina |
United States | The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine | Columbus | Ohio |
United States | Premier Health - Miami Valley Hospital | Dayton | Ohio |
United States | University of South Carolina Greenville | Greenville | South Carolina |
United States | University of Texas Health Science Center | Houston | Texas |
United States | Cedars Sinai Medical Center | Los Angeles | California |
United States | Columbia University Irving Medical Center | New York | New York |
United States | Christiana Care | Newark | Delaware |
United States | Eastern Virginia Medical School | Norfolk | Virginia |
United States | University of Pittsburgh | Pittsburgh | Pennsylvania |
United States | Brown University | Providence | Rhode Island |
United States | University of California San Francisco | San Francisco | California |
United States | University of South Florida | Tampa | Florida |
United States | University of Alabama | Tuscaloosa | Alabama |
United States | Wake Forest University | Winston-Salem | North Carolina |
Lead Sponsor | Collaborator |
---|---|
Ohio State University | Patient-Centered Outcomes Research Institute, The George Washington University Biostatistics Center |
United States,
Venkatesh KK, Chiang CW, Castillo WC, Battarbee AN, Donneyong M, Harper LM, Costantine M, Saade G, Werner EF, Boggess KA, Landon MB. Changing patterns in medication prescription for gestational diabetes during a time of guideline change in the USA: a cross-sectional study. BJOG. 2022 Feb;129(3):473-483. doi: 10.1111/1471-0528.16960. Epub 2021 Nov 8. — View Citation
Venkatesh KK, Lynch CD, Powe CE, Costantine MM, Thung SF, Gabbe SG, Grobman WA, Landon MB. Risk of Adverse Pregnancy Outcomes Among Pregnant Individuals With Gestational Diabetes by Race and Ethnicity in the United States, 2014-2020. JAMA. 2022 Apr 12;327(14):1356-1367. doi: 10.1001/jama.2022.3189. — View Citation
Venkatesh KK, Wu J, Trinh A, Cross S, Rice D, Powe CE, Brindle S, Andreatta S, Bartholomew A, MacPherson C, Costantine MM, Saade G, McAlearney AS, Grobman WA, Landon MB. Patient Priorities, Decisional Comfort, and Satisfaction with Metformin versus Insulin for the Treatment of Gestational Diabetes Mellitus. Am J Perinatol. 2023 Dec 4. doi: 10.1055/s-0043-1777334. Online ahead of print. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | A neonatal composite adverse outcome of large-for-gestational-age (LGA) birthweight, hypoglycemia, hyperbilirubinemia, and/or death. | LGA will be defined as a birthweight =90th%tile for gestational age based on a US birth certificate reference adjusted for parity and/or fetal sex. Neonatal hypoglycemia will be defined as a blood glucose <35 mg/dL or treatment <24 hours after birth with either IV, PO, or gel glucose therapy. Neonatal hyperbilirubinemia will be defined as treated with phototherapy or exchange transfusion in the first postnatal week and either treatment in the first postnatal week or kernicterus. Fetal or neonatal death can be due to any indication between randomization to hospital discharge or 30 days postnatal if still hospitalized (excluding voluntary pregnancy termination). | LGA at birth. Hypoglycemia <24 hours after birth. Hyperbilirubinemia within the first week after birth. Death between randomization to hospital discharge or 30 days postnatal. | |
Primary | Child body mass index (BMI) at 2 years of age | Child BMI measured in kg/m2 as a continuous measure standardized using U.S. CDC reference adjusted for child sex | 2 years of age. | |
Secondary | Hypertensive disorder of pregnancy, HDP (maternal) | HDP will include either gestational hypertension or preeclampsia. Gestational hypertension will be defined as: systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm Hg or more on two occasions at least 4 hours apart after 20 weeks of gestation in a woman with a previously normal blood pressure. Preeclampsia will be defined as: above blood pressure criteria AND proteinuria (300 mg or more per 24 hour urine collection, protein/creatinine ratio of 0.3 mg/dL or more, or dipstick reading of 2+) OR thrombocytopenia (platelet count less than 100 109/L), renal insufficiency (serum creatinine greater than 1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease), impaired liver function (elevated blood concentrations of liver transaminases to twice normal concentration), pulmonary edema, new-onset headache or visual symptoms not attributed to other diagnoses. | Randomization to delivery | |
Secondary | Gestational weight gain (maternal) | Gestational weight gain between weight at first prenatal visit and weight at delivery based on z-score and defined as excess versus within Institute of Medicine (IOM) recommendations based on first pregnancy BMI. | Initiation of prenatal care to delivery | |
Secondary | Mode of delivery (maternal) | Cesarean delivery or vaginal delivery | At birth | |
Secondary | Obstetric perineal/anal sphincter injuries (maternal) | First degree: Injury to perineal skin only; Second degree: Injury to perineum involving perineal muscles but not involving anal sphincter; Third degree: Injury to perineum involving anal sphincter complex, including 3a: Less than 50% of external anal sphincter thickness torn; 3b: More than 50% external anal sphincter thickness torn; and 3c: Both external anal sphincter and internal anal sphincter torn; and Fourth degree: Injury to perineum involving anal sphincter complex (external anal sphincter and internal anal sphincter) and anal epithelium. | At birth | |
Secondary | Preterm birth (child) | Preterm birth <37 weeks and <34 weeks based on project gestational age | At birth | |
Secondary | Requiring mechanical ventilation (child) | Intubation, continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) for ventilation or cardiopulmonary resuscitation within first 72 hours of birth | <72 hours after birth | |
Secondary | NICU admission (child) | Admitted to NICU or intermediate nursery =72 hours, any indication | Birth to delivery discharge. | |
Secondary | Oxygen support (child) | Requiring oxygen support | <72 hours after birth | |
Secondary | Respiratory distress syndrome (child) | Signs of respiratory distress with oxygen requirement and confirmed by chest x-ray. | Anytime during the first 72 hours after birth | |
Secondary | Body mass index (BMI) (maternal) | Continuous measure, using standardized protocol as kg/m2. | 2-year follow-up | |
Secondary | Obesity overall and by class (maternal) | BMI per the following classifications: Normal or underweight: < 25 kg/m2; Overweight: 25 to < 30 kg/m2; Class 1: 30 to < 35 kg/m2; Class 2: 35 to < 40 kg/m2; and Class 3: 40 kg/m2 or greater. | 2-year follow-up | |
Secondary | Anthropometry (maternal) | Waist circumference, continuous measures in cm | 2-year follow-up | |
Secondary | Anthropometry (maternal) | Hip circumference, continuous measures in cm | 2-year follow-up | |
Secondary | Anthropometry (maternal) | Waist - to - hip ratio, continuous measure | 2-year follow-up | |
Secondary | Adiposity (maternal) | Triceps, subscapular, suprailiac skinfolds, continuous measures in cm | 2 year follow-up | |
Secondary | Type 2 diabetes (maternal) | A1c > 6.5% OR fasting plasma glucose > 126 mg/dL OR OGTT > 200 mg/dL OR prior diagnosis per patient report | 2-year follow-up. | |
Secondary | Prediabetes (maternal) | A1c 5.7% to 6.4% OR fasting plasma glucose 100 mg/dl to 125 mg/dL OR OGTT 140 to 199 mg/dL | 2-year follow-up. | |
Secondary | Hypertension (maternal) | Per American Heart Association criteria as below and/or antihypertensive medication or prior diagnosis per patient report, and defined as: Elevated: Systolic between 120-129 and diastolic less than 80 mm Hg; Stage 1: Systolic between 130-139 or diastolic between 80-89 mm Hg; and Stage 2: Systolic at least 140 or diastolic at least 90 mm Hg. | 2-year follow-up. | |
Secondary | Cholesterol (maternal) | Fasting state, defined as a continuous measure and dichotomous at the following thresholds for each component: Total cholesterol: > 200 mg/dL; LDL cholesterol: > mg/dL; HDL cholesterol: < 40 mg/dL; Triglycerides: > 200 mg/dL. | 2-year follow-up. | |
Secondary | Hemoglobin A1c (maternal) | Continuous measure, percentage. | 2-year follow-up. | |
Secondary | Overweight (child) | BMI =85th%tile for age and sex. | 2-year follow-up. | |
Secondary | Obesity (child) | BMI =95th%tile for age and sex. | 2-year follow-up. | |
Secondary | Anthropometry (child) | Abdominal circumference; age- and sex-adjusted per WHO z-scores for arm circumference. | 2-year follow-up. | |
Secondary | Adiposity (child) | Triceps/subscapular skinfold thickness > 90th%tile for age and sex; individual and sum of measures. | 2-year follow-up. | |
Secondary | Treatment Satisfaction Questionnaire for Medication (TSQM) | The TSQM (version 1.4) comprises 14 items across four domains focusing on effectiveness (three items), side effects (five items), convenience (three items), and global satisfaction (three items) of the medication over the previous 2-3 weeks. With the exception of item 4 (presence of side effects; yes or no), all items have five or seven responses, scored from one (least satisfied) to five or seven (most satisfied). Item scores are summed to give four domain scores, which are in turn transformed to a scale of 0-100. Item 4 was not included for scoring. | 6-weeks postpartum. | |
Secondary | Questionnaire on Acceptability of Treatment | A set of 5 questions developed in the Rowan et al. RCT assessing patient adherence, preferences, and experiences with metformin versus insulin for GDM (Rowan et al., NEJM, 2008). | 6-weeks postpartum. |
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