Clinical trial NCT01990612: A Randomized Trial of Induction Versus Expectant Management
Official title: Induction in Nulliparous Women at 39 Weeks to Prevent Adverse Outcomes: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Labor and Delivery
Keywords: Induction of labor
Expectant management of labor
39 weeks gestation
Lead sponsor: The George Washington University Biostatistics Center
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-11-21
Enrollment: 6106
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized trial of 6000 women at 38 weeks 0 days to 38 weeks 6 days randomized to one of two arms: elective induction of labor between 39 weeks 0 days and 39 weeks 4 days; or expectant management (unless a medical indication arises) until at least 40 weeks 5 days.
Primary purpose: PREVENTION

Brief summary: A randomized clinical trial to assess whether elective induction of labor at 39 weeks of gestation compared with expectant management will improve outcomes.

Detailed description: Given the reported increased risks of adverse events in pregnancies extending beyond 39 weeks it has been hypothesized that a policy of planned elective induction at 39 weeks could improve outcomes for the infant and the mother. For multiparous patients, especially those with a favorable cervix, it is perhaps easy to justify an elective induction at 39 weeks given the low risk of cesarean section. However, for nulliparous patients the current evidence, derived mainly from retrospective observational studies, does not allow a clear recommendation. Nevertheless, a trend towards an increased rate of elective labor induction in pregnancies at 39 weeks has been reported, indicating that practitioners are more commonly using elective induction at this gestational age,even as others caution against routine elective induction prior to 41 weeks given the reported increased risk of cesarean delivery. Ultimately, a randomized controlled trial is necessary to satisfactorily understand whether elective induction of labor of nulliparas at 39 weeks improves neonatal and maternal outcomes.

Eligibility criteria: Inclusion Criteria:

1. Nulliparous - no previous pregnancy beyond 20 weeks
2. Singleton gestation. Twin gestation reduced to singleton, either spontaneously or therapeutically, is not eligible unless the reduction occurred before 14 weeks project gestational age.
3. Gestational age at randomization between 38 weeks 0 days and 38 weeks 6 days inclusive based on clinical information and evaluation of the earliest ultrasound.

Exclusion Criteria:

1. Project gestational age at date of first ultrasound is \> 20 weeks 6 days
2. Plan for induction of labor prior to 40 weeks 5 days
3. Plan for cesarean delivery or contraindication to labor
4. Breech presentation
5. Signs of labor (regular painful contractions with cervical change)
6. Fetal demise or known major fetal anomaly
7. Heparin or low-molecular weight heparin during the current pregnancy
8. Placenta previa, accreta, vasa previa
9. Active vaginal bleeding greater than bloody show
10. Ruptured membranes
11. Cerclage in current pregnancy
12. Known oligohydramnios, defined as AFI \< 5 or MVP \< 2
13. Fetal growth restriction, defined as EFW \< 10th percentile
14. Known HIV positivity because of modified delivery plan
15. Major maternal medical illness associated with increased risk for adverse pregnancy outcome (for example, any diabetes mellitus, lupus, any hypertensive disorder, cardiac disease, renal insufficiency)
16. Refusal of blood products
17. Participation in another interventional study that influences management of labor at delivery or perinatal morbidity or mortality
18. Delivery planned elsewhere at a non-Network site

Primary outcomes:
measure: Composite of Severe Neonatal Morbidity and Perinatal Mortality
timeFrame: delivery through 72 hours after birth
measure: Perinatal Death (Component of Primary Outcome)
timeFrame: antepartum pregnancy period through hospital discharge
measure: Number of Participant Infants Requiring Respiratory Support (Component of Primary Outcome)
timeFrame: Delivery through discharge
measure: Number of Infants With Apgar Score ≤3 at 5 Minutes (Component of Primary Outcome)
timeFrame: Delivery through 5 minutes after birth
measure: Number of Infants With Neonatal Hypoxic-ischemic Encelphalopathy (Component of Primary Outcome)
timeFrame: delivery through discharge
measure: Number of Infants With Neonatal Seizure (Component of Primary Outcome)
timeFrame: Delivery through discharge
measure: Number of Infants With Neonatal Infection (Component of Primary Outcome)
timeFrame: delivery through discharge
measure: Number of Infants With Meconium Aspiration Syndrome (Component of Primary Outcome)
timeFrame: Delivery through discharge
measure: Number of Infants With Birth Trauma (Component of Primary Outcome)
timeFrame: During the Delivery process
measure: Number of Infants With Intracranial or Subgaleal Hemorrhage (Component of Primary Outcome)
timeFrame: delivery through disharge
measure: Hypotension Requiring Vasopressor Support (Component of Primary Outcome)
timeFrame: delivery through discharge
Secondary outcomes:
measure: Number of Participants With Cesarean Delivery
timeFrame: delivery
measure: Number of Participants Who Had Uterine Incisional Extension at Cesarean Delivery
timeFrame: delivery
measure: Participants Who Had Operative Vaginal Delivery
timeFrame: delivery
measure: Number of Participants Who Had Chorioamnionitis
timeFrame: at any time from randomization through delivery
measure: Number of Participants With Third or Fourth Degree Perineal Laceration
timeFrame: delivery
measure: Number of Maternal Deaths
timeFrame: from randomization to hospital discharge
measure: Number of Participants Admitted to Intensive Care Unit (ICU)
timeFrame: delivery through hospital discharge
measure: Number of Participants Experiencing Hypertensive Disorder of Pregnancy
timeFrame: Randomization to hospital discharge
measure: Number of Participants With Postpartum Hemorrhage
timeFrame: delivery through hospital discharge
measure: Labor Agentry Scale Scores
timeFrame: Between 6 hours after delivery and 8 weeks after delivery
measure: Labor Pain Scores
timeFrame: During labor and delivery
measure: Number of Participants With Maternal Postpartum Infection
timeFrame: delivery through discharge
measure: Number of Participants With Venous Thromboembolism
timeFrame: delivery through discharge
measure: Number of Participants With Indications for Cesarean Delivery
timeFrame: Labor and delivery
measure: Duration of Respiratory Support
timeFrame: delivery through hospital discharge
measure: Number of Infants With Cephalohematoma
timeFrame: delivery through hospital discharge
measure: Shoulder Dystocia
timeFrame: delivery
measure: Number of Infants Who Had Transfusion of Blood Products or Blood
timeFrame: delivery through hospital discharge
measure: Number of Infants With Hyperbilirubinemia
timeFrame: delivery through discharge
measure: Number of Infants With Neonatal Hypoglycemia
timeFrame: delivery through discharge
measure: Number Infants Admitted to NICU or Intermediate Care
timeFrame: delivery through hospital discharge
measure: Number of Hours on the Labor and Delivery Unit
timeFrame: Hours from admission to L&D to discharge from L&D
measure: Maternal Postpartum Length of Hospital Stay
timeFrame: delivery through hospital discharge
measure: Neonatal Length of Hospital Stay
timeFrame: delivery through hospital discharge
measure: Number of Participants With Indications for Operative Vaginal Delivery
timeFrame: Labor and delivery
measure: Number of Participants and Breastfeeding Status at 4-8 Weeks After Delivery
timeFrame: 4-8 weeks after delivery
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Chicago
country: United States
facility: Northwestern University-Prentice Hospital
state: Illinois
city: New York
country: United States
facility: Columbia University-St. Luke's Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee Womens Hospital of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Brown University
state: Rhode Island
city: Dallas
country: United States
facility: Dept of OB/GYN, Southwestern Medical Center, University of Texas
state: Texas
city: Galveston
country: United States
facility: University of Texas - Galveston
state: Texas
city: Houston
country: United States
facility: University of Texas - Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Menachem Miodovnik, MD
role: STUDY_DIRECTOR
affiliation: The George Washington University Biostatistics Center
name: Rebecca Clifton, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: William Grobman, MD
role: STUDY_CHAIR
References:
citation: Grobman WA, Rice MM, Reddy UM, Tita ATN, Silver RM, Mallett G, Hill K, Thom EA, El-Sayed YY, Perez-Delboy A, Rouse DJ, Saade GR, Boggess KA, Chauhan SP, Iams JD, Chien EK, Casey BM, Gibbs RS, Srinivas SK, Swamy GK, Simhan HN, Macones GA; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Labor Induction versus Expectant Management in Low-Risk Nulliparous Women. N Engl J Med. 2018 Aug 9;379(6):513-523. doi: 10.1056/NEJMoa1800566.
citation: Costantine MM, Sandoval GJ, Grobman WA, Reddy UM, Tita ATN, Silver RM, El-Sayed YY, Wapner RJ, Rouse DJ, Saade GR, Thorp JM Jr, Chauhan SP, Chien EK, Casey BM, Srinivas SK, Swamy GK, Simhan HN; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. Association of Body Mass Index With the Use of Health Care Resources in Low-Risk Nulliparous Pregnancies After 39 Weeks of Gestation. Obstet Gynecol. 2022 May 1;139(5):866-876. doi: 10.1097/AOG.0000000000004753. Epub 2022 Apr 5.
citation: Silver RM, Rice MM, Grobman WA, Reddy UM, Tita ATN, Mallett G, Hill K, Thom EA, El-Sayed YY, Wapner RJ, Rouse DJ, Saade GR, Thorp JM Jr, Chauhan SP, Chien EK, Casey BM, Gibbs RS, Srinivas SK, Swamy GK, Simhan HN, Macones GA; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network*. Customized Probability of Vaginal Delivery With Induction of Labor and Expectant Management in Nulliparous Women at 39 Weeks of Gestation. Obstet Gynecol. 2020 Oct;136(4):698-705. doi: 10.1097/AOG.0000000000004046.
citation: Mallett G, Hill K, de Voest J, Bousleiman SZ, Allard D, Harris S, Salazar A, Clark K, Ortiz F, Bartholomew A, Dalton W, Craig J, Bickus M; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Characteristics Associated With Consent and Reasons for Declining in a Randomized Trial in Pregnancy. Obstet Gynecol. 2020 Oct;136(4):731-737. doi: 10.1097/AOG.0000000000003998.
citation: El-Sayed YY, Rice MM, Grobman WA, Reddy UM, Tita ATN, Silver RM, Mallett G, Hill K, Thom EA, Wapner RJ, Rouse DJ, Saade GR, Thorp JM Jr, Chauhan SP, Chien EK, Casey BM, Gibbs RS, Srinivas SK, Swamy GK, Simhan HN, Macones GA; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network*. Elective Labor Induction at 39 Weeks of Gestation Compared With Expectant Management: Factors Associated With Adverse Outcomes in Low-Risk Nulliparous Women. Obstet Gynecol. 2020 Oct;136(4):692-697. doi: 10.1097/AOG.0000000000004055.
citation: Dude A, Fette LM, Reddy UM, Tita ATN, Silver RM, El-Sayed YY, Wapner RJ, Rouse DJ, Saade GR, Thorp JM Jr, Chauhan SP, Iams JD, Chien EK, Casey BM, Srinivas SK, Swamy GK, Simhan HN; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Maternal Sense of Control During Childbirth and Infant Feeding Method. Obstet Gynecol. 2020 Mar;135(3):583-590. doi: 10.1097/AOG.0000000000003697.