A Randomized Trial of Induction Versus Expectant Management (ARRIVE)

Induction in Nulliparous Women at 39 Weeks to Prevent Adverse Outcomes: A Randomized Controlled Trial

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

Study Overview

• Status: Completed
• Conditions: Labor and Delivery
• Intervention / Treatment: Procedure: Elective Induction of Labor

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.

• Study Type: Interventional
• Enrollment (Actual): 6106
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama - Birmingham
  • California
    • Stanford, California, United States, 94305-5317
      • Stanford University
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University-Prentice Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University-St. Luke's Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina - Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • Case Western Reserve University
    • Columbus, Ohio, United States, 43210
      • Ohio State University Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee Womens Hospital of UPMC
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Brown University
  • Texas
    • Dallas, Texas, United States, 75235-9032
      • Dept of OB/GYN, Southwestern Medical Center, University of Texas
    • Galveston, Texas, United States, 77555
      • University of Texas - Galveston
    • Houston, Texas, United States, 77030
      • University of Texas - Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Expectant Management; Expectant management (unless a medical indication arises) until at least 40 weeks 5 days.
OTHER: Elective Induction of Labor; Elective induction of labor between 39 weeks 0 days and 39 weeks 4 days	Procedure: Elective Induction of Labor; Women randomized to induction of labor will undergo induction via oxytocin at 39 weeks 0 days to 39 weeks 4 days. Those with an unfavorable cervix (modified Bishop score < 5) will first undergo cervical ripening (method left to the discretion of the patient's physician) in conjunction with or followed by oxytocin stimulation unless a contraindication arises.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of Severe Neonatal Morbidity and Perinatal Mortality	Includes any one of: Perinatal death; Need for respiratory support within 72 hours after birth; Apgar score of 3 or less at 5 minutes; Hypoxic-ischemic encephalopathy; Seizure; Infection (confirmed sepsis or pneumonia); Meconium aspiration system; Birth trauma (bone fracture, neurologic injury or retinal hemorrhage); Intracranial or subaleal hemorrhage; Hypotension requiring vasopressor support	delivery through 72 hours after birth
Perinatal Death (Component of Primary Outcome)	Perinatal death includes antepartum stillbirth, intrapartum stillbirth and neonatal death	antepartum pregnancy period through hospital discharge
Number of Participant Infants Requiring Respiratory Support (Component of Primary Outcome)	Respiratory support includes mechanical ventilation, continuous positive airway pressure or high flow nasal cannula and cardiorespiratory resuscitation	Delivery through discharge
Number of Infants With Apgar Score ≤3 at 5 Minutes (Component of Primary Outcome)	The Apgar score is based on a total score of 1 to 10. The higher the score, the better the baby is doing after birth. A score of 7, 8, or 9 is normal and is a sign that the newborn is in good health.	Delivery through 5 minutes after birth
Number of Infants With Neonatal Hypoxic-ischemic Encelphalopathy (Component of Primary Outcome)		delivery through discharge
Number of Infants With Neonatal Seizure (Component of Primary Outcome)		Delivery through discharge
Number of Infants With Neonatal Infection (Component of Primary Outcome)	Neonatal infection includes confirmed sepsis and/or confirmed pneumonia	delivery through discharge
Number of Infants With Meconium Aspiration Syndrome (Component of Primary Outcome)		Delivery through discharge
Number of Infants With Birth Trauma (Component of Primary Outcome)	Birth trauma includes clavicular, skull or other fracture; brachial plexus palsy, facial nerve palsy, retinal hemorrhage or vocal cord paralysis	During the Delivery process
Number of Infants With Intracranial or Subgaleal Hemorrhage (Component of Primary Outcome)	Intracranial or subgaleal hemorrhage includes Intraventricular hemorrhage grades III or IV, subdural hematoma, subarachnoid hematoma, and subgaleal hematoma	delivery through disharge
Hypotension Requiring Vasopressor Support (Component of Primary Outcome)		delivery through discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Cesarean Delivery		delivery
Number of Participants Who Had Uterine Incisional Extension at Cesarean Delivery	Incisional extensions at cesarean section, including J shape or T shape; or cervical traumas	delivery
Participants Who Had Operative Vaginal Delivery		delivery
Number of Participants Who Had Chorioamnionitis	Chorioamnionitis, defined as a clinical diagnosis before delivery	at any time from randomization through delivery
Number of Participants With Third or Fourth Degree Perineal Laceration		delivery
Number of Maternal Deaths	Maternal death at anytime between randomization and hospital discharge.	from randomization to hospital discharge
Number of Participants Admitted to Intensive Care Unit (ICU)	Admission of the participant to the intensive care unit (ICU)	delivery through hospital discharge
Number of Participants Experiencing Hypertensive Disorder of Pregnancy		Randomization to hospital discharge
Number of Participants With 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; Curettage	delivery through hospital discharge
Labor Agentry Scale Scores	Scores on the Labor Agentry Scale range from 29 to 203, with higher scores indicating greater perceived control during childbirth; included are women who had spontaneous labor, labor that started spontaneously but then was augmented, or induced labor.	Between 6 hours after delivery and 8 weeks after delivery
Labor Pain Scores	Labor pain was scored according to a 10-point Likert scale, with higher scores indicating greater pain; included are women who had spontaneous labor, labor that started spontaneously but then was augmented, or induced labor.	During labor and delivery
Number of Participants With Maternal Postpartum Infection	Defined as any of the following: Clinical diagnosis of endometritis; Wound reopened for hematoma, seroma, infection or other reasons; Cellulitis requiring antibiotics; Pneumonia; Pyelonephritis; Bacteremia - unknown source; Septic pelvic thrombosis	delivery through discharge
Number of Participants With Venous Thromboembolism	Maternal deep venous thrombosis or pulmonary embolism	delivery through discharge
Number of Participants With Indications for Cesarean Delivery	Number of participants with indications for cesarean delivery including dystocia, non-reassuring fetal status or other indication	Labor and delivery
Duration of Respiratory Support	including ventilator, CPAP, high-flow nasal cannula (HFNC)	delivery through hospital discharge
Number of Infants With Cephalohematoma		delivery through hospital discharge
Shoulder Dystocia		delivery
Number of Infants Who Had Transfusion of Blood Products or Blood		delivery through hospital discharge
Number of Infants With Hyperbilirubinemia	Hyperbilirubinemia requiring phototherapy or exchange transfusion	delivery through discharge
Number of Infants With Neonatal Hypoglycemia	glucose < 35 mg/dl and requiring IV therapy	delivery through discharge
Number Infants Admitted to NICU or Intermediate Care	Number infants admitted to intensive care unit (NICU) or intermediate care unit	delivery through hospital discharge
Number of Hours on the Labor and Delivery Unit	Median duration of stay in labor and delivery unit	Hours from admission to L&D to discharge from L&D
Maternal Postpartum Length of Hospital Stay		delivery through hospital discharge
Neonatal Length of Hospital Stay		delivery through hospital discharge
Number of Participants With Indications for Operative Vaginal Delivery	Number of participants with indications for operative vaginal delivery including dystocia, non-reassuring fetal status and other indications	Labor and delivery
Number of Participants and Breastfeeding Status at 4-8 Weeks After Delivery	Breastfeeding status includes breastfeeding, breastfeeding and formula feeding, or formula feeding	4-8 weeks after delivery

Collaborators and Investigators

• Sponsor: The George Washington University Biostatistics Center
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Study Director: Menachem Miodovnik, MD, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Study Chair: William Grobman, MD, Northwestern University

Publications and helpful links

General Publications

• 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.
• 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; 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): November 1, 2017
• Study Completion (ACTUAL): January 1, 2018

Study Registration Dates

• First Submitted: November 15, 2013
• First Submitted That Met QC Criteria: November 15, 2013
• First Posted (ESTIMATE): November 21, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 21, 2019
• Last Update Submitted That Met QC Criteria: February 19, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Induction of labor; Expectant management of labor; 39 weeks gestation
• Other Study ID Numbers: HD36801-ARRIVE; U10HD036801 (U.S. NIH Grant/Contract); UG1HD087230 (U.S. NIH Grant/Contract); UG1HD027869 (U.S. NIH Grant/Contract); UG1HD040500 (U.S. NIH Grant/Contract); UG1HD034208 (U.S. NIH Grant/Contract); UG1HD027915 (U.S. NIH Grant/Contract); UG1HD040485 (U.S. NIH Grant/Contract); UG1HD053097 (U.S. NIH Grant/Contract); UG1HD040544 (U.S. NIH Grant/Contract); UG1HD040545 (U.S. NIH Grant/Contract); UG1HD040560 (U.S. NIH Grant/Contract); UG1HD040512 (U.S. NIH Grant/Contract); UG1HD087192 (U.S. NIH Grant/Contract); UG1HD068282 (U.S. NIH Grant/Contract); UG1HD068258 (U.S. NIH Grant/Contract); UG1HD068268 (U.S. NIH Grant/Contract); UG1HD034116 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The dataset will be shared per NIH policy after the completion and publication of the main analyses. Requests for datasets can be sent to mfmudatasets@bsc.gwu.edu.