Antibiotic Prophylaxis to Prevent Obesity-Related Induction Complications in Nulliparae at Term 2.0

Antibiotic Prophylaxis to Prevent Obesity-Related Induction Complications in Nulliparae at Term 2.0 (APPOINT 2.0): A Multi-center Randomized Controlled Trial

Obesity increases the risk of pregnancy complications, including puerperal infections and cesarean delivery, and risk rises with increasing body mass index (BMI). Since obese women are more likely to have comorbidities that would necessitate delivery prior to their due date (i.e. prior to 40 weeks gestation), and class III obesity specifically is an indication for delivery by 39 weeks, these patients have a high rate of labor induction. In nulliparous women from the general population (obese and non-obese), labor induction at 39 weeks (compared to expectant management) is associated with less maternal morbidity and a lower cesarean rate. Researchers previously conducted a pilot randomized placebo-controlled trial in obese, nulliparous women undergoing labor induction at term and found that the cesarean delivery rate was lower in women who received a prophylactic antibiotic regimen during labor compared with those who received the placebo. Researchers proposed multi-center trial aims to test this hypothesis in a large sample with adequate power to determine whether prophylactic antibiotics during labor are associated with a decrease in the rate of cesarean delivery in term, nulliparous, obese women. If the findings from the pilot trial are confirmed, this would represent a novel intervention to decrease the cesarean delivery rate in a subset of women at highest risk for cesarean-related complications.

Study Overview

• Status: Recruiting
• Conditions: Labor Complication; Obesity in Pregnancy
• Intervention / Treatment: Drug: Azithromycin; Drug: Placebo

Detailed Description

This is a multi-center randomized placebo-controlled trial in which nulliparous women with obesity who are undergoing induction of labor at term and not receiving IAP for GBS will be recruited (n=787). The participants will be randomized 1:1 to receive either prophylactic antibiotics during their labor induction (azithromycin 500 milligrams intravenously once and cefazolin 2 grams intravenously every 8 hours for up to three doses) or like-appearing placebos. The participants and their obstetrical providers will be blinded to the study intervention. The study will be conducted with an identical protocol at six study sites. Trained research nurses/assistants at each study site will consent and enroll participants, collect biospecimens, and collect demographic information and data on pregnancy and neonatal outcomes, and will convey this data to the primary site for analysis.

Researchers hypothesize that the group that receives the study drug regimen of prophylactic antibiotics during induction of labor will have a lower rate of cesarean delivery than the group that receives the placebo. They also hypothesize that the group that receives the study drug regimen will have a lower rate of puerperal infection than the placebo group.

Nulliparous women with obesity who are undergoing induction of labor at term will be eligible for participation in the study. Across all sites, 787 total subjects will be recruited.

• Study Type: Interventional
• Enrollment (Estimated): 787
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christy Zornes, MHR; Phone Number: 48137 405-271-8001; Email: christy-zornes@ouhsc.edu
• Study Contact Backup: Name: Stephanie Pierce, MD; Phone Number: 405-271-8787; Email: stephanie-pierce@ouhsc.edu

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • University of Oklahoma Health Sciences Center
      • Contact: Christy Zornes, MHR; Phone Number: 48137 405-271-8001; Email: christy-zornes@ouhsc.edu
      • Contact: Kyra Woods, BA; Phone Number: 45750 405-271-8001; Email: kyra-woods@ouhsc.edu
      • Principal Investigator: Stephanie Pierce, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• BMI ≥30
• No prior deliveries at or beyond 20 weeks gestation
• Undergoing induction of labor
• Gestational age 37 weeks or more
• Age 15-45
• Not receiving IAP for GBS prophylaxis

Exclusion Criteria:

• Fetal death prior to labor induction
• Known fetal anomaly
• Multiple gestation
• Ruptured membranes for more than 12 hours
• Chorioamnionitis or other infection requiring antibiotics at the start of the labor induction
• Previous myometrial surgery
• Allergy to azithromycin or beta-lactam antibiotics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prophylactic antibiotics; Azithromycin 500 milligrams intravenously once and cefazolin 2 grams intravenously every 8 hours for up to three doses	Drug: Azithromycin; Azithromycin 500 milligrams intravenously once and cefazolin 2 grams intravenously every 8 hours for up to three doses; Other Names: Cefazolin
Placebo Comparator: Placebo; Placebos, similar in appearance, in place of azithromycin and cefazolin	Drug: Placebo; Placebo given in place of other two active drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of cesarean delivery	Determine whether a prophylactic antibiotic regimen during labor induction will decrease the rate of cesarean delivery in obese, nulliparous women undergoing induction of labor	30 days postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of chorioamnionitis development	Defined clinically by fever and maternal and fetal signs such as tachycardia and uterine tenderness	30 days postpartum
Rate of endometritis	Maternal development of endometritis	30 days postpartum
Rate of cesarean wound infection	Rate of maternal would infection from cesarean section	30 days postpartum
Rate of postpartum hemorrhage	Rate of maternal postpartum hemorrhage	30 days postpartum
Rate of blood transfusion	Rate of maternal blood transfusions	30 days postpartum
Rate of intensive care unit admission	Maternal admission into intensive care unit	30 days postpartum
Rate of hospital readmission	Maternal hospital readmission after delivery	30 days postpartum
Rate of indications for cesarean delivery	Rate of indications for a cesarean delivery	30 days postpartum
Maternal hospital stay	Length of maternal hospital stay	30 days postpartum
Neonate hospital stay	Length of neonatal hospital stay	30 days postpartum
Rate of NICU admission	Neonatal intensive care unit (NICU) admission	30 days postpartum
APGAR score	5-minute APGAR score <4 (neonate)	30 days postpartum
Rate of respiratory distress syndrome	Development of infant respiratory distress syndrome	30 days postpartum
Rate of sepsis	Infant sepsis (either suspected or confirmed)	30 days postpartum
Rate of necrotizing enterocolitis	Infant necrotizing enterocolitis	30 days postpartum
Periventricular leukomalacia	Development of periventricular leukomalacia in infant as seen by ultrasound	30 days postpartum
Rate of intraventricular hemorrhage	Intraventricular hemorrhage grade III or higher	30 days postpartum
Neonatal death	Death of neonate	30 days postpartum

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: University of Alabama at Birmingham; Duke University; University of Florida; University of Utah; Case Western Reserve University
• Investigators: Principal Investigator: Stephanie Pierce, MD, University of Oklahoma

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: May 28, 2024
• First Submitted That Met QC Criteria: June 28, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Nutrition Disorders; Female Urogenital Diseases and Pregnancy Complications; Overnutrition; Body Weight; Pregnancy Complications; Overweight; Obesity; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obstetric Labor Complications; Pregnancy in Obesity; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; Macrolides; Lactones; beta-Lactams; Lactams; Cephalosporins; Thiazines; Erythromycin; Polyketides; Cefazolin; Azithromycin
• Other Study ID Numbers: APPOINT 2.0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No