Study of Pregnancy And Neonatal Health (SPAN)

Gestational Diabetes Mellitus Clinical Trial

— SPAN  

Official title:

Study of Pregnancy And Neonatal Health (SPAN): TIMing of dElivery (TIME) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05515744
• Other study ID #: 10000737
• Secondary ID: 000737-CH
• Status: Recruiting
• Phase: N/A
• Start date: January 20, 2023
• Est. completion date: December 31, 2027

Study information

• Verified date: September 2023
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Katherine L Grantz, MD, MS
• Phone: (301) 435-6935
• Email: katherine.grantz[@]nih.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6450
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes Mellitus

Intervention

Procedure:
• Childbirth
Induction or planned cesarean

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Duke University Perinatal Research Center	Durham	North Carolina
United States	INOVA Fairfax Hospital	Falls Church	Virginia
United States	Intermountain Healthcare	Murray	Utah
United States	Ochsner Baptist	New Orleans	Louisiana
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Utah	Salt Lake City	Utah

Sponsors (10)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Duke University, Inova Fairfax Hospital, Intermountain Health Care, Inc., Ochsner Health System, Technical Resources International, Inc., University of Alabama at Birmingham, University of North Carolina, Chapel Hill, University of Pennsylvania, University of Utah

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of Neonatal Morbidity and Perinatal Mortality		Hospital discharge
Primary	Occurrence of Antepartum, intrapartum or neonatal death (Component of primary outcome)		Antepartum pregnancy period through Newborn Discharge
Primary	Incidence of moderate or higher neonatal respiratory support within 72 hours after birth (Component of primary outcome)	Including any of the following: Nasal cannula >/= 2 LPM (liters per minute), Nasal continuous positive airway pressure (NCPAP), NIPPV; (non-invasive intermittent positive pressure ventilation; Note that NIPPV is more general than Bilevel positive airway pressure (BiPAP) i.e. BiPAP is a form of NIPPV, as is non-invasive NAVA, synchronized NIPPV, non-synchronized NIPPV, some ventilators can do nasal IMV in certain situations, etc.), Mechanical ventilation, High frequency ventilation, and ECMO/ECLS (extracorporeal mechanical support/extracorporeal life support)	Delivery through Newborn Discharge
Primary	Occurrence of Pneumonia (Component of primary outcome)	Confirmed by X-ray or positive blood culture	Delivery through Newborn Discharge
Primary	Occurrence of Meconium aspiration syndrome (Component of primary outcome)	Respiratory distress in an infant born through meconium-stained amniotic fluid with X-ray findings consistent with meconium aspiration syndrome, and whose symptoms could not be otherwise explained	Delivery through Newborn Discharge
Primary	Occurrence of Sepsis (Component of primary outcome)	The diagnosis of sepsis will require the presence of a clinically ill infant in whom systemic infection is suspected with a positive blood, CSF, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal X-ray confirming infection.	Delivery through Newborn Discharge
Primary	Occurrence of Neonatal encephalopathy (Component of primary outcome)	Defined by Shankaran et al. 2005	Delivery through Newborn Discharge
Primary	Occurrence of Intracranial hemorrhage (Component of primary outcome)	Intraventricular hemorrhage grades III and IV, subgaleal hematoma, subdural hematoma, or subarachnoid hematoma	Delivery through Newborn Discharge
Primary	Occurrence of Seizures (Component of primary outcome)		Delivery through Newborn Discharge
Primary	Occurrence of Birth trauma (Component of primary outcome)	Bone fractures, brachial plexus palsy, other neurologic injury, retinal hemorrhage, or facial nerve palsy	Delivery through Newborn Discharge
Primary	Occurrence of Hypotension requiring pressor support (Component of primary outcome)		Delivery through Newborn Discharge
Primary	Occurrence of hypertrophic cardiomyopathy (Component of primary outcome)		Delivery through Newborn Discharge
Primary	Incidence of neonatal intensive care unit (NICU) > 1 day (24 hours) stay	NICU stay > 1 day (24 hours)	Delivery through Newborn Discharge
Secondary	Incidence of respiratory support less than moderate	Hood oxygen and Nasal cannula <2 LPM (liters per minute); Other than room air (No support)	Delivery through Newborn Discharge
Secondary	Duration of any respiratory support		Delivery through Newborn Discharge
Secondary	Duration of moderate respiratory support		Delivery through Newborn Discharge
Secondary	Occurrence of Transient tachypnea of the newborn		Delivery through Newborn Discharge
Secondary	Occurrence of Respiratory distress syndrome in Neonates	Both a clinical diagnosis and whether required surfactant	Delivery through Newborn Discharge
Secondary	Occurrence of Hypoglycemia in neonates	Glucose < 35 mg/dl) and whether required IV therapy	Delivery through Newborn Discharge
Secondary	Occurrence of Hyperbilirubinemia in Neonates	Requiring phototherapy or exchange transfusion in Neonates	Delivery through Newborn Discharge
Secondary	Occurrence of Polycythemia in Neonates	Both a clinical diagnosis and whether required partial exchange transfusion	Delivery through Newborn Discharge
Secondary	Incidence of Therapeutic hypothermia	Head or body cooling	Delivery through Newborn Discharge
Secondary	Incidence of Transfusion of blood products or blood in neonates		Delivery through Newborn Discharge
Secondary	Occurrence of neonatal intensive care unit (NICU) or intermediate care unit admission		Delivery through Newborn Discharge
Secondary	Duration of Neonatal hospital stay	Measured in days	Delivery through Newborn Discharge
Secondary	Birthweight		Delivery through Newborn Discharge
Secondary	Incidence of small for gestational age	Defined as < 10th percentile using the Duryea reference	Delivery through Newborn Discharge
Secondary	Incidence of large for gestational age and macrosomia	LGA defined as > 90th percentile using the Duryea reference and macrosomia defined as birthweight > 4500 g	Delivery through Newborn Discharge
Secondary	Composite of Maternal Morbidity and Mortality	Maternal death, HELLP syndrome, Eclampsia, Pulmonary edema, placental abruption, blood transfusion	Pregnancy through Discharge
Secondary	Occurrence of maternal death		Pregnancy through Discharge
Secondary	Occurrence of HELLP syndrome	As defined by American College of Obstetricians and Gynecologists (ACOG)	Pregnancy through Discharge
Secondary	Occurrence of Eclampsia	As defined by American College of Obstetricians and Gynecologists (ACOG)	Pregnancy through Discharge
Secondary	Occurrence of Maternal Pulmonary edema	Chest x-ray confirmed	Pregnancy through Discharge
Secondary	Occurrence of Placental abruption		Pregnancy through Delivery
Secondary	Incidence of Maternal Blood transfusion		Pregnancy through Discharge
Secondary	Incidence of spontaneous labor		Pregnancy through Delivery
Secondary	Incidence of induced labor		Pregnancy through Delivery
Secondary	Incidence of planned cesarean		Pregnancy through Delivery
Secondary	Indication for delivery including cesarean for suspected macrosomia	Defined as estimated fetal weight > 4500 grams	Pregnancy through Delivery
Secondary	Occurrence of Spontaneous vaginal delivery		Pregnancy through Delivery
Secondary	Occurrence of Operative vaginal delivery	Vacuum or forceps	Pregnancy through Delivery
Secondary	Occurrence of Cesarean delivery		Pregnancy through Delivery
Secondary	Indications for operative vaginal delivery		Pregnancy through Delivery
Secondary	Indication for cesarean		Pregnancy through Delivery
Secondary	Incidence of Shoulder dystocia		Delivery through Newborn Discharge
Secondary	Occurrence of Maternal lacerations	1st, 2nd, 3rd or 4th degree perineal; sulcus, vaginal wall; labial, periurethral, clitoral, abrasion, other	Delivery through Discharge
Secondary	Occurrence of Postpartum hemorrhage	Defined as any of the following: Transfusion, Non-elective hysterectomy, Use of two or more uterotonics other than oxytocin, Other surgical interventions such as uterine compression sutures, uterine artery ligation, embolization, hypogastric ligation, or balloon tamponade, and Curettage	Delivery through Discharge
Secondary	Occurrence of Maternal ICU Admission		Delivery through Discharge
Secondary	Incidence of Maternal venous thromboembolism	Deep venous thrombosis or pulmonary embolism	Delivery through Discharge
Secondary	Incidence of Chorioamnionitis	Defined as a clinical diagnosis before delivery	Delivery through Discharge
Secondary	Maternal postpartum infection	Defined as, Clinical diagnosis of endometritis, Wound reopened for hematoma, seroma, infection or other reasons, Cellulitis requiring antibiotics, Pneumonia, Pyelonephritis, Bacteremia unknown source, and Septic pelvic thrombosis	Delivery through Discharge
Secondary	Maternal hypertension	Mild and Severe (systolic and diastolic) defined by ACOG	Delivery through Discharge
Secondary	Incidence of Preeclampsia, with or without severe features	Defined by ACOG	Delivery through Discharge
Secondary	Use of antihypertensive drugs	Includes oral antihypertensive, intravenous antihypertensive, or intravenous anticonvulsant	Delivery through Discharge
Secondary	Number of hours in labor and delivery unit		Delivery through Discharge
Secondary	Duration of maternal hospital stay	Measured in Days.	Pregnancy through Newborn Discharge