Antibiotic Prophylaxis to Prevent Obesity-Related Induction Complications in Nulliparae at Term (APPOINT)

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

Obesity increases the risk of pregnancy complications, including among others puerperal infections and cesarean delivery, and risk rises with increasing body mass index (BMI). Class III obesity is an indication for delivery by 39 weeks, and 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 morbidity and a lower cesarean rate. Antibiotic prophylaxis, standard before cesarean delivery, is associated with less post-cesarean infection if azithromycin is added to the standard cefazolin. In this placebo-controlled pilot trial, investigators will estimate the parameters necessary to calculate the sample size for a planned multicenter clinical trial of prophylactic antibiotics administered at the start of labor inductions of morbidly obese nulliparous women at term.

Study Overview

• Status: Completed
• Conditions: Obesity; Induction of Labor Affected Fetus / Newborn
• Intervention / Treatment: Drug: Cefazolin; Drug: Azithromycin; Drug: Placebo

Detailed Description

Investigators will enroll consenting women delivering at The Children's Hospital at OU Medical Center who meet enrollment criteria. Flyers will be distributed to providers to give to women who may be eligible for the study at prenatal visits, so that they may review the information prior to presenting for their induction of labor. Labor induction may be a scheduled procedure. However, many inductions occur in an unscheduled fashion due to medical or obstetric indications. Therefore, it is difficult to predict which women will ultimately require labor induction and at what gestational age they will require it, so it is not feasible to approach and consent all women during a clinic visit prior to labor induction. Distribution of flyers will allow patients to have information about the study prior to presenting for labor induction. Furthermore, unlike women in spontaneous labor, women being consented just prior to a labor induction are not vulnerable in the same way as one might consider a patient in labor, since they will not have the distraction and discomfort of uterine contractions that are presenting in laboring patients.

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

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

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 either drug used in the protocol (cefazolin or azithromycin)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cefazolin + Azithromycin; Women will be randomized 1:1 to receive cefazolin 2 grams intravenously at the start of the labor induction and every 8 hours thereafter for a maximum of three doses and azithromycin 500 mg intravenously once at the start of the labor induction	Drug: Cefazolin; intravenous drugs used as prophylactic antibiotics; Drug: Azithromycin; prophylactic antibiotic
Placebo Comparator: Placebo + Placebo; Women will be randomized 1:1 to receive placebo intravenously at the start of the labor induction and every 8 hours thereafter for a maximum of three doses and placebo intravenously once at the start of the labor induction	Drug: Placebo; Intravenous saline; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Cesarean Delivery	Rate at which women give birth via cesarean section	30 days after delivery
Number of Participants With Puerperal Infections	Chorioamnionitis, endometritis and/or cesarean wound infection	30 days after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Postpartum Hemorrhage	Experience of postpartum hemorrhage	30 days after delivery
Number of Participants Who Underwent A Blood Transfusion	Need of a blood transfusion	30 days after delivery
Number of Participants With ICU Admission	Intensive care unit admission	30 days after delivery
Number of Participants With Maternal Hospital Readmission	Maternal hospital readmission within 30 days after delivery	30 days after delivery
Primary Indications for Cesarean Delivery	Nonreassuring fetal status, failed induction, active-phase arrest, second-stage arrest, or other	30 days after delivery
Neonatal Outcomes	Neonatal complications	30 days after delivery

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Investigators: Principal Investigator: Stephanie Pierce, MD, University of Oklahoma

Publications and helpful links

General Publications

• Pierce SL, Peck JD, Zornes C, Standerfer E, Edwards RK. Antibiotic Prophylaxis to Prevent Obesity-Related Induction Complications in Nulliparae at Term: a pilot randomized controlled trial. Am J Obstet Gynecol MFM. 2022 Sep;4(5):100681. doi: 10.1016/j.ajogmf.2022.100681. Epub 2022 Jun 18.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: January 9, 2019
• First Submitted That Met QC Criteria: January 10, 2019
• First Posted (Actual): January 11, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Anti-Infective Agents; Anti-Bacterial Agents; Cefazolin; Azithromycin
• Other Study ID Numbers: 9939 (FHCRC)

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