Glycemic Targets for Pregnant Women With GDM and T2DM

Study Overview
=================
Brief Summary
-----------------
The purpose of this randomized clinical trial is to determine whether glycemic targets that are lower than those currently recommended by the American Diabetes Association (ADA) and the American College of Obstetricians and Gynecologists (ACOG) would improve overall outcomes in pregnant patients with diabetes. Eligible pregnant women with a diagnosis of gestational diabetes or Type 2 diabetes will be randomized into either routine care with glycemic targets as currently recommended by ADA and ACOG (control arm), or more aggressive care with lower glycemic targets that more closely resemble normoglycemia in pregnancy (intervention arm). The glycemic targets for the control arm will be defined as follows: fasting ≤95 mg/dL, pre-prandial ≤95 mg/dL, and 1-hour postprandial ≤140 mg/dL. The glycemic targets for the intervention arm will be defined as follows: fasting ≤80 mg/dL, pre-prandial ≤80 mg/dL, and 1-hour postprandial ≤110 mg/dL. The primary outcome will be a 250-gram difference in birth weight between the two study arms. Secondary maternal and neonatal outcomes of interest will also be compared between the two study arms.

Official Title
-----------------
Tight Versus Standard Glycemic Targets for Pregnant Women With Gestational Diabetes and Type 2 Diabetes

Conditions
-----------------
Diabetes Mellitus in Pregnancy, Diabetes, Gestational, Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Other: Glycemic Targets


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women with a singleton gestation 18 years or older Diagnosis of gestational diabetes (prior to 34 weeks gestational age) or Type 2 diabetes Exclusion Criteria: Diagnosed with gestational diabetes at or beyond 34 weeks gestational age Type 1 diabetes Diabetic retinopathy Diabetic nephropathy Diabetic vasculopathy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible women will be randomized at a 1:1 ratio (using block randomization) into either the control arm or the intervention arm. It is understood that study participants, physicians, and nurse-educators cannot be blinded to group allocation. The randomization process will proceed as follows. A primary randomization model assigning patients to the New Target versus the Standard Target will be created for the one center (LAC+USC), and permuted-block randomization with random allocation will be used. The investigators will be blinded to the block size. The generation of randomization codes will be performed using SAS statistical software, v. 9.3, Cary, NC. A validation test will be performed to assure that treatment balance is achieved within the entire study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Arm<br>Patients in the control arm will be instructed to check blood sugars seven times per day: fasting, pre-prandial, and 1 hour after each meal. The glycemic targets for the control arm will be defined as follows: fasting ≤95 mg/dL, pre-prandial ≤95 mg/dL, and 1-hour postprandial ≤140 mg/dL (i.e. conventional targets). Patients who do not achieve glycemic goals with diet and exercise will be started on medical therapy (metformin or insulin) at the discretion of a maternal-fetal medicine subspecialist and endocrinologist. | |
| Experimental: Interventional Arm<br>Patients in the experimental arm will be instructed to check blood sugars seven times per day: fasting, pre-prandial, and 1 hour after each meal. The glycemic targets for the intervention arm will be defined as follows: fasting ≤80 mg/dL, pre-prandial ≤80 mg/dL, and 1-hour postprandial ≤110 mg/dL. Patients who do not achieve glycemic goals with diet and exercise will be started on medical therapy (metformin or insulin) at the discretion of a maternal-fetal medicine subspecialist and endocrinologist. | Other: Glycemic Targets<br>* The intervention is glycemic targets that are lower than those currently recommended by ADA and ACOG: fasting ≤80 mg/dL, pre-prandial ≤80 mg/dL, and 1-hour postprandial ≤110 mg/dL instead of fasting ≤95 mg/dL, pre-prandial ≤95 mg/dL, and 1-hour postprandial ≤140 mg/dL.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in birth weight | 250-gram difference in birth weight | 41 weeks gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total prenatal care visits | Total number of prenatal care visits during pregnancy | 41 weeks gestation | 
| Prenatal care visits after enrollment | Number of prenatal care visits after enrollment | 41 weeks gestation | 
| Prenatal care visits: log/glucometer | Number of prenatal care visits with log/glucometer available for RN or MD to review | 41 weeks gestation | 
| Prenatal care visits: targets met | Number of prenatal care visits in which patient met blood sugar targets | 41 weeks gestation | 
| Prenatal care visits: intervention | Number of prenatal care visits in which an intervention for blood sugars was recommended (e.g. starting medication or changing medication dose) | 41 weeks gestation | 
| Symptomatic hypoglycemia | Frequency of symptomatic hypoglycemia episodes (hypoglycemia defined as <70 mg/dL per ADA) | 41 weeks gestation | 
| Asymptomatic hypoglycemia | Frequency of asymptomatic hypoglycemia episodes (hypoglycemia defined as <70 mg/dL per ADA) | 41 weeks gestation | 
| A1c enrollment | Hemoglobin A1c at the time of enrollment | At time of enrollment (up to 34 weeks gestation) | 
| A1c 36 weeks | Hemoglobin A1c at 36 weeks gestational age | At 36 weeks gestational age | 
| Lowest recorded blood sugar | Lowest recorded blood sugar during prenatal care | 41 weeks gestation | 
| Highest recorded blood sugar | Highest recorded blood sugar during prenatal care | 41 weeks gestation | 
| Average recorded blood sugar | Average recorded blood sugar during prenatal care | 41 weeks gestation | 
| Weekly compliance | Average number of blood sugar checks actually performed each week | 41 weeks gestation | 
| Weekly target assessment | % of blood sugars within goal each week | 41 weeks gestation | 
| Diabetes medication | Did the patient need diabetes medication (including oral agents and insulin) during antepartum period? | 41 weeks gestation | 
| Intrapartum insulin | Did the patient need insulin during the intrapartum period? | From onset of induction/labor until delivery | 
| Gestational weight gain | Total weight gain during pregnancy in kilograms | 41 weeks gestation | 
| Antepartum admission | Was the patient ever admitted to antepartum service for any indication, including poorly-controlled diabetes or diabetes-related complication? | 41 weeks gestation | 
| Corticosteroids | Did the patient receive antenatal corticosteroid treatment? | 41 weeks gestation | 
| Oligohydramnios | Amniotic fluid index <5 cm or maximum vertical pocket <2cm | 41 weeks gestation | 
| Polyhydramnios | Amniotic fluid index >24cm or maximum vertical pocket >8cm | 41 weeks gestation | 
| Fetal growth restriction | Ultrasonographic estimated fetal weight or abdominal circumference <10% for gestational ag | 41 weeks gestation | 
| Gestational age at delivery | Gestational age at delivery | During intrapartum admission to Labor & Delivery | 
| Induction of labor | Did the patient undergo induction of labor? | During intrapartum admission to Labor & Delivery | 
| Mode of delivery | primary cesarean section, repeat cesarean section, vaginal delivery, vaginal delivery with vacuum, vaginal delivery with forceps | During intrapartum admission to Labor & Delivery | 
| Cesarean indication | If the patient had cesarean delivery, what was the indication? | During intrapartum admission to Labor & Delivery | 
| TOLAC | Did the patient attempt a trial of labor after cesarean? | During intrapartum admission to Labor & Delivery | 
| Blood loss | Quantitative blood loss (or estimated if quantitative is unknown) in cc's | During intrapartum admission to Labor & Delivery | 
| 3rd or 4th degree laceration | 3rd or 4th degree perineal laceration | During intrapartum admission to Labor & Delivery | 
| PIH | Pregnancy-induced hypertension (gestational hypertension, preeclampsia, HELLP syndrome) | From 20 weeks gestation until 30 days postpartum | 
| Hypertensive emergency | Did the patient have severe-range blood pressures require antihypertensive medication? | From conception until 30 days postpartum | 
| Chorioamnionitis | Chorioamnionitis | During intrapartum admission to Labor & Delivery | 
| Endometritis | Endometritis | Within 30 days postpartum | 
| VTE | Venous thromboembolism: deep venous thrombosis or pulmonary embolism | From conception until 30 days postpartum | 
| Length of stay (maternal) | Length of hospital admission for labor, delivery, and postpartum | From admission to Labor & Delivery until discharge from postpartum | 
| Postpartum readmission | Did the patient get readmitted within 30 days of delivery? | Within 30 days postpartum | 
| Postpartum wound complication | Cesarean wound infection of dehiscence, perineal laceration breakdown | Within 30 days postpartum | 
| Cardiac complications | Did the patient develop any cardiac complications such as arrhythmias or cardiomyopathy? | From conception until 30 days postpartum | 
| Seizures | Did any maternal seizures occur during the pregnancy or postpartum? | From conception until 30 days postpartum | 
| Macrosomia | Birth weight >4000 grams | Within 24 hours of birth | 
| LGA | Large for gestational age (birth weight ≥90% for gestational age) | Within 24 hours of birth | 
| SGA | Small for gestational age (birth weight <10% for gestational age) | Within 24 hours of birth | 
| Shoulder dystocia | Shoulder dystocia | During intrapartum admission to Labor & Delivery | 
| Apgar | 5-minute Apgar score | 5 minutes after birth | 
| Cord gas pH <7.0 | Did the baby have a cord blood gas pH <7.0? | Within 24 hours of birth | 
| Base excess | What was the base excess on the cord blood gas? | Within 24 hours of birth | 
| Neonatal blood glucose | What was the neonatal serum blood glucose at birth? | Within 24 hours of birth | 
| RDS | Neonatal respiratory distress syndrome | Within 30 days of delivery | 
| TTN | Transient tachypnea of the newborn | Within 30 days of delivery | 
| Hyperbilirubinemia | Neonatal hyperbilirubinemia (as defined in AAP 2004 Clinical Practice Guideline Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation) | Within 30 days of delivery | 
| Neonatal sepsis | Neonatal sepsis | Within 30 days of delivery | 
| NICU | NICU admission | Within 30 days of delivery | 
| Length of stay (neonatal) | How many days after birth did the neonate stay in the hospital? | From birth until discharge (up to 1 year) | 
| Congenital anomaly | Congenital anomaly | Within 30 days of delivery | 
| IUFD or stillbirth | Intrauterine fetal demise or stillbirth | From conception until delivery |