Clinical trial NCT05515744: Study of Pregnancy And Neonatal Health (SPAN)
Official title: Study of Pregnancy And Neonatal Health (SPAN): TIMing of dElivery (TIME) Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Gestational Diabetes Mellitus
Keywords: Gestational Diabetes Mellitus
Delivery Timing
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: Ochsner Health System
name: University of Pennsylvania
name: Intermountain Health Care, Inc.
name: Duke University
name: Inova Fairfax Hospital
name: University of Utah
name: University of Alabama at Birmingham
name: University of North Carolina, Chapel Hill
name: Technical Resources International, Inc.
First posted: 2022-08-25
Enrollment: 6450
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will conduct a randomized trial among women with gestational diabetes (GDM). Study of Pregnancy And Neonatal health (SPAN), TIMing of dElivery (TIME) is a randomized trial that will recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery. Women with GDM who are approached for the trial and are found eligible but do not consent to participating in randomization for delivery will be asked to consent for chart review only (estimated additional n=3,000). The primary objective is to determine the best time to initiate delivery for GDM-complicated deliveries (defined as the time when risk of illness and death for the newborn is the lowest) between 37-39 weeks.

Detailed description: This is a randomized clinical trial under an adaptive design nested in a larger observational study, among women who are diagnosed with uncontrolled gestational diabetes mellitus (GDM). Women from multiple clinical sites around the United States will be recruited into the study (n=3,450). Women with GDM who are approached for the trial and are found eligible but do not consent to participating to randomization for delivery will be asked to consent for chart review only (estimated additional n=3,000). The primary objective is to determine the optimal time to initiate delivery for GDM complicated deliveries (defined as the time when neonatal morbidity and perinatal mortality risk is the lowest) between 37-39 weeks (n=3,450 women). Newborn developmental and behavior outcomes, and anthropometric measures will also be assessed as secondary outcomes, as well as an exploratory analysis to investigate whether there are clinical, non-clinical or biochemical factors such as glucose measures that will further assist in refining the interval for optimizing time of GDM complicated deliveries relative to neonatal morbidity and perinatal mortality.

Eligibility criteria: INCLUSION CRITERIA:

Aim 3 (GDM randomized trial, TIME) inclusion criteria:

Women inclusion criteria:

1. Age ≥ 18 Years
2. Verified diagnosis of Gestational Diabetes Mellitus (GDM) with abnormal glucose levels\*\*\* or meeting other criteria for poor control, specifically any one of the following: Estimated fetal weight ≥90th percentile (LGA), Polyhydramnios, and or Demonstrate noncompliance or nonadherence as defined clinically, including missing visits, not keeping accurate log, etc.

   \*\*\*One or more elevated fasting blood glucoses OR three or more elevated post-prandial blood glucoses after receiving education about appropriate diet and lifestyle modification (e.g. physical activity)
3. Accurate gestational age as verified by ultrasound
4. Singleton gestation
5. English or Spanish speaker
6. Plans to deliver at the study site hospital
7. Ability to provide informed consent to be randomized to initiation of delivery

EXCLUSION CRITERIA:

Aim 3 (GDM randomized trial, TIME) exclusion criteria:

1. Pre-gestational diabetes\*

   \*will be defined as diabetes diagnosis before pregnancy OR before 13 weeks of gestation with a documented fasting plasma glucose ≥ 126 mg/dL, random plasma glucose ≥ 200 mg/dL, 2 hour post glucose ≥ 200 mg/dL during an oral glucose tolerance test (75 g glucose load), or hemoglobin A1c ≥ 6.5%.110.
2. Previous stillbirth defined as fetal demise ≥ 20 weeks of gestation
3. Self-reported history of alcohol dependency disorder and/or other drug/substance dependency in the past year
4. Teratogen exposure (e.g. cyclophosphamide, valproic acid, warfarin)
5. Known infectious diseases associated with neonatal morbidity (e.g. malaria, cytomegalovirus, rubella, toxoplasmosis, syphilis or Zika virus)
6. Genetic disorders, aneuploidy and known major fetal anomalies
7. Fetal demise
8. Pregnancies with concurrent conditions and other indications for earlier delivery will also be excluded.
9. Participation in another interventional study that influences management of labor and delivery or perinatal morbidity or mortality

Primary outcomes:
measure: Composite of Neonatal Morbidity and Perinatal Mortality
timeFrame: Hospital discharge
measure: Occurrence of Antepartum, intrapartum or neonatal death (Component of primary outcome)
timeFrame: Antepartum pregnancy period through Newborn Discharge
measure: Incidence of moderate or higher neonatal respiratory support within 72 hours after birth (Component of primary outcome)
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Pneumonia (Component of primary outcome)
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Meconium aspiration syndrome (Component of primary outcome)
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Sepsis (Component of primary outcome)
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Neonatal encephalopathy (Component of primary outcome)
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Intracranial hemorrhage (Component of primary outcome)
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Seizures (Component of primary outcome)
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Birth trauma (Component of primary outcome)
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Hypotension requiring pressor support (Component of primary outcome)
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of hypertrophic cardiomyopathy (Component of primary outcome)
timeFrame: Delivery through Newborn Discharge
measure: Incidence of neonatal intensive care unit (NICU) > 1 day (24 hours) stay
timeFrame: Delivery through Newborn Discharge
Secondary outcomes:
measure: Incidence of respiratory support less than moderate
timeFrame: Delivery through Newborn Discharge
measure: Duration of any respiratory support
timeFrame: Delivery through Newborn Discharge
measure: Duration of moderate respiratory support
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Transient tachypnea of the newborn
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Respiratory distress syndrome in Neonates
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Hypoglycemia in neonates
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Hyperbilirubinemia in Neonates
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Polycythemia in Neonates
timeFrame: Delivery through Newborn Discharge
measure: Incidence of Therapeutic hypothermia
timeFrame: Delivery through Newborn Discharge
measure: Incidence of Transfusion of blood products or blood in neonates
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of neonatal intensive care unit (NICU) or intermediate care unit admission
timeFrame: Delivery through Newborn Discharge
measure: Duration of Neonatal hospital stay
timeFrame: Delivery through Newborn Discharge
measure: Birthweight
timeFrame: Delivery through Newborn Discharge
measure: Incidence of small for gestational age
timeFrame: Delivery through Newborn Discharge
measure: Incidence of large for gestational age and macrosomia
timeFrame: Delivery through Newborn Discharge
measure: Composite of Maternal Morbidity and Mortality
timeFrame: Pregnancy through Discharge
measure: Occurrence of maternal death
timeFrame: Pregnancy through Discharge
measure: Occurrence of HELLP syndrome
timeFrame: Pregnancy through Discharge
measure: Occurrence of Eclampsia
timeFrame: Pregnancy through Discharge
measure: Occurrence of Maternal Pulmonary edema
timeFrame: Pregnancy through Discharge
measure: Occurrence of Placental abruption
timeFrame: Pregnancy through Delivery
measure: Incidence of Maternal Blood transfusion
timeFrame: Pregnancy through Discharge
measure: Incidence of spontaneous labor
timeFrame: Pregnancy through Delivery
measure: Incidence of induced labor
timeFrame: Pregnancy through Delivery
measure: Incidence of planned cesarean
timeFrame: Pregnancy through Delivery
measure: Indication for delivery including cesarean for suspected macrosomia
timeFrame: Pregnancy through Delivery
measure: Occurrence of Spontaneous vaginal delivery
timeFrame: Pregnancy through Delivery
measure: Occurrence of Operative vaginal delivery
timeFrame: Pregnancy through Delivery
measure: Occurrence of Cesarean delivery
timeFrame: Pregnancy through Delivery
measure: Indications for operative vaginal delivery
timeFrame: Pregnancy through Delivery
measure: Indication for cesarean
timeFrame: Pregnancy through Delivery
measure: Incidence of Shoulder dystocia
timeFrame: Delivery through Newborn Discharge
measure: Occurrence of Maternal lacerations
timeFrame: Delivery through Discharge
measure: Occurrence of Postpartum hemorrhage
timeFrame: Delivery through Discharge
measure: Occurrence of Maternal ICU Admission
timeFrame: Delivery through Discharge
measure: Incidence of Maternal venous thromboembolism
timeFrame: Delivery through Discharge
measure: Incidence of Chorioamnionitis
timeFrame: Delivery through Discharge
measure: Maternal postpartum infection
timeFrame: Delivery through Discharge
measure: Maternal hypertension
timeFrame: Delivery through Discharge
measure: Incidence of Preeclampsia, with or without severe features
timeFrame: Delivery through Discharge
measure: Use of antihypertensive drugs
timeFrame: Delivery through Discharge
measure: Number of hours in labor and delivery unit
timeFrame: Delivery through Discharge
measure: Duration of maternal hospital stay
timeFrame: Pregnancy through Newborn Discharge
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: New Orleans
country: United States
facility: Ochsner Baptist
state: Louisiana
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Perinatal Research Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Murray
country: United States
facility: Intermountain Healthcare
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Falls Church
country: United States
facility: INOVA Fairfax Hospital
state: Virginia
Study officials:
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Katherine L Grantz, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: