Induction of Labor Affected Fetus / Newborn, Obesity
Conditions
Brief summary
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.
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.
Interventions
DRUGCefazolin
intravenous drugs used as prophylactic antibiotics
DRUGPlacebo
Intravenous saline
DRUGAzithromycin
prophylactic antibiotic
Sponsors
University of Oklahoma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
One arm includes double placebo drugs that will be blinded from the investigator and participant
Intervention model description
Randomized controlled clinical trial
Eligibility
Sex/Gender
FEMALE
Age
15 Years to 45 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Cesarean Delivery | 30 days after delivery | Rate at which women give birth via cesarean section |
| Number of Participants With Puerperal Infections | 30 days after delivery | Chorioamnionitis, endometritis and/or cesarean wound infection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ICU Admission | 30 days after delivery | Intensive care unit admission |
| Number of Participants With Maternal Hospital Readmission | 30 days after delivery | Maternal hospital readmission within 30 days after delivery |
| Number of Participants With Postpartum Hemorrhage | 30 days after delivery | Experience of postpartum hemorrhage |
| Neonatal Outcomes | 30 days after delivery | Neonatal complications |
| Primary Indications for Cesarean Delivery | 30 days after delivery | Nonreassuring fetal status, failed induction, active-phase arrest, second-stage arrest, or other |
| Number of Participants Who Underwent A Blood Transfusion | 30 days after delivery | Need of a blood transfusion |
Countries
United States
Participant flow
Recruitment details
Researchers enrolled women delivering at The Children's Hospital at OU Medical Center who met enrollment criteria and consented to study participation. Patients were given information about the study during a third trimester prenatal care visit. However, they were enrolled in the hospital before their labor induction is started.
Participants by arm
| Arm | Count |
|---|---|
| Cefazolin + Azithromycin Women were 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
Cefazolin: intravenous drugs used as prophylactic antibiotics
Azithromycin: prophylactic antibiotic | 93 |
| Placebo + Placebo Women were 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
Placebo: Intravenous saline | 93 |
| Total | 186 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 2 |
Baseline characteristics
| Characteristic | Cefazolin + Azithromycin | Placebo + Placebo | Total |
|---|---|---|---|
| Age, Customized Age (y) | 26.9 years STANDARD_DEVIATION 5.6 | 25.3 years STANDARD_DEVIATION 5.2 | 26.1 years STANDARD_DEVIATION 5.4 |
| BMI ≥30 Class I (BMI, 30-34 kg/m^2) | 19 Participants | 19 Participants | 38 Participants |
| BMI ≥30 Class II (BMI, 35-39 kg/m^2) | 23 Participants | 24 Participants | 47 Participants |
| BMI ≥30 Class III (BMI, ≥40 kg/m^2) | 51 Participants | 50 Participants | 101 Participants |
| Chronic hypertension | 9 Participants | 8 Participants | 17 Participants |
| Diabetes mellitus Gestational | 10 Participants | 11 Participants | 21 Participants |
| Diabetes mellitus Pregestational | 8 Participants | 5 Participants | 13 Participants |
| Fetal growth restriction | 1 Participants | 3 Participants | 4 Participants |
| Gestational age 37 weeks or more | 271.4 days STANDARD_DEVIATION 8.4 | 271.7 days STANDARD_DEVIATION 6.2 | 271.6 days STANDARD_DEVIATION 7.3 |
| Gestational hypertension | 32 Participants | 18 Participants | 50 Participants |
| Preeclampsia | 19 Participants | 22 Participants | 41 Participants |
| Race/Ethnicity, Customized Race and ethnicity Asian | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Race and ethnicity Black | 7 Participants | 9 Participants | 16 Participants |
| Race/Ethnicity, Customized Race and ethnicity Hispanic | 16 Participants | 18 Participants | 34 Participants |
| Race/Ethnicity, Customized Race and ethnicity Native American | 7 Participants | 11 Participants | 18 Participants |
| Race/Ethnicity, Customized Race and ethnicity Not reported | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Race and ethnicity Other | 2 Participants | 5 Participants | 7 Participants |
| Race/Ethnicity, Customized Race and ethnicity White | 57 Participants | 46 Participants | 103 Participants |
| Region of Enrollment United States | 93 participants | 93 participants | 186 participants |
| Sex/Gender, Customized Female participants | 93 Participants | 93 Participants | 186 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 93 | 0 / 93 |
| other Total, other adverse events | 4 / 93 | 0 / 93 |
| serious Total, serious adverse events | 0 / 93 | 0 / 93 |
Outcome results
Primary
Number of Participants With Cesarean Delivery
Rate at which women give birth via cesarean section
Time frame: 30 days after delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cefazolin + Azithromycin | Number of Participants With Cesarean Delivery | 27 Participants |
| Placebo + Placebo | Number of Participants With Cesarean Delivery | 37 Participants |
Primary
Number of Participants With Puerperal Infections
Chorioamnionitis, endometritis and/or cesarean wound infection
Time frame: 30 days after delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cefazolin + Azithromycin | Number of Participants With Puerperal Infections | 8 Participants |
| Placebo + Placebo | Number of Participants With Puerperal Infections | 9 Participants |
Secondary
Neonatal Outcomes
Neonatal complications
Time frame: 30 days after delivery
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cefazolin + Azithromycin | Neonatal Outcomes | Periventricular leukomalacia | 0 Participants |
| Cefazolin + Azithromycin | Neonatal Outcomes | Neonatal death | 0 Participants |
| Cefazolin + Azithromycin | Neonatal Outcomes | NICU admission | 11 Participants |
| Cefazolin + Azithromycin | Neonatal Outcomes | Respiratory distress syndrome | 8 Participants |
| Cefazolin + Azithromycin | Neonatal Outcomes | Intubation required within first 72 hours | 1 Participants |
| Cefazolin + Azithromycin | Neonatal Outcomes | Hyperbilirubinemia requiring phototherapy | 41 Participants |
| Cefazolin + Azithromycin | Neonatal Outcomes | Suspected or confirmed sepsis | 11 Participants |
| Cefazolin + Azithromycin | Neonatal Outcomes | Culture with organisms identified | 0 Participants |
| Cefazolin + Azithromycin | Neonatal Outcomes | Necrotizing enterocolitis | 0 Participants |
| Cefazolin + Azithromycin | Neonatal Outcomes | Intraventricular hemorrhage grade III or higher | 0 Participants |
| Cefazolin + Azithromycin | Neonatal Outcomes | Neonatal complications composite | 50 Participants |
| Placebo + Placebo | Neonatal Outcomes | Periventricular leukomalacia | 0 Participants |
| Placebo + Placebo | Neonatal Outcomes | Neonatal death | 0 Participants |
| Placebo + Placebo | Neonatal Outcomes | NICU admission | 10 Participants |
| Placebo + Placebo | Neonatal Outcomes | Suspected or confirmed sepsis | 8 Participants |
| Placebo + Placebo | Neonatal Outcomes | Neonatal complications composite | 42 Participants |
| Placebo + Placebo | Neonatal Outcomes | Culture with organisms identified | 0 Participants |
| Placebo + Placebo | Neonatal Outcomes | Respiratory distress syndrome | 7 Participants |
| Placebo + Placebo | Neonatal Outcomes | Intraventricular hemorrhage grade III or higher | 0 Participants |
| Placebo + Placebo | Neonatal Outcomes | Intubation required within first 72 hours | 3 Participants |
| Placebo + Placebo | Neonatal Outcomes | Necrotizing enterocolitis | 0 Participants |
| Placebo + Placebo | Neonatal Outcomes | Hyperbilirubinemia requiring phototherapy | 37 Participants |
Secondary
Number of Participants Who Underwent A Blood Transfusion
Need of a blood transfusion
Time frame: 30 days after delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cefazolin + Azithromycin | Number of Participants Who Underwent A Blood Transfusion | 4 Participants |
| Placebo + Placebo | Number of Participants Who Underwent A Blood Transfusion | 4 Participants |
Secondary
Number of Participants With ICU Admission
Intensive care unit admission
Time frame: 30 days after delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cefazolin + Azithromycin | Number of Participants With ICU Admission | 1 Participants |
| Placebo + Placebo | Number of Participants With ICU Admission | 0 Participants |
Secondary
Number of Participants With Maternal Hospital Readmission
Maternal hospital readmission within 30 days after delivery
Time frame: 30 days after delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cefazolin + Azithromycin | Number of Participants With Maternal Hospital Readmission | 1 Participants |
| Placebo + Placebo | Number of Participants With Maternal Hospital Readmission | 2 Participants |
Secondary
Number of Participants With Postpartum Hemorrhage
Experience of postpartum hemorrhage
Time frame: 30 days after delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cefazolin + Azithromycin | Number of Participants With Postpartum Hemorrhage | 16 Participants |
| Placebo + Placebo | Number of Participants With Postpartum Hemorrhage | 16 Participants |
Secondary
Primary Indications for Cesarean Delivery
Nonreassuring fetal status, failed induction, active-phase arrest, second-stage arrest, or other
Time frame: 30 days after delivery
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cefazolin + Azithromycin | Primary Indications for Cesarean Delivery | Failed induction | 11 Participants |
| Cefazolin + Azithromycin | Primary Indications for Cesarean Delivery | Second-stage arrest | 1 Participants |
| Cefazolin + Azithromycin | Primary Indications for Cesarean Delivery | Active-phase arrest | 2 Participants |
| Cefazolin + Azithromycin | Primary Indications for Cesarean Delivery | Other | 1 Participants |
| Cefazolin + Azithromycin | Primary Indications for Cesarean Delivery | Nonreassuring fetal status | 12 Participants |
| Placebo + Placebo | Primary Indications for Cesarean Delivery | Other | 2 Participants |
| Placebo + Placebo | Primary Indications for Cesarean Delivery | Nonreassuring fetal status | 14 Participants |
| Placebo + Placebo | Primary Indications for Cesarean Delivery | Failed induction | 11 Participants |
| Placebo + Placebo | Primary Indications for Cesarean Delivery | Active-phase arrest | 6 Participants |
| Placebo + Placebo | Primary Indications for Cesarean Delivery | Second-stage arrest | 4 Participants |