Ampicillin / Sulbactam vs. Ampicillin / Gentamicin for Treatment of Chorioamnionitis

Comparison of Ampicillin / Sulbactam vs. Ampicillin / Gentamicin for Treatment of Intrapartum Chorioamnionitis: a Randomized Controlled Trial

Chorioamnionitis is an infection of the placenta and amniotic membranes (bag of waters) surrounding the baby inside of a pregnant woman prior to delivery. This infection is somewhat common and is routinely treated with antibiotics given to the mother both before and after the baby is born. Currently it is not known what is the best choice of antibiotics to treat this type of infection, but commonly used treatments include Unasyn (ampicillin/sulbactam) or ampicillin/gentamicin. We plan to compare these two different antibiotic regimens to see if one is better than the other at treating and preventing bad outcomes from chorioamnionitis in women and babies.

Study Overview

• Status: Completed
• Conditions: Chorioamnionitis
• Intervention / Treatment: Drug: Unasyn; Drug: Ampicillin/gentamicin

Detailed Description

Patients who meet inclusion criteria will be approached upon admission to Labor and Delivery. A study staff member will describe the study and offer participation. If a patient agrees to participate, she will sign research protocol and HIPAA consent forms and receive a copy of these forms. The patient's chart will be flagged, indicating that she is a study participant. The patient's prenatal care and labor and delivery will be managed by her physician per standard of care at the physician's discretion, including routine intrapartum treatment of Group B streptococcus (GBS) colonization using ampicillin. When a participating patient is diagnosed with chorioamnionitis, she will be randomized in a blinded fashion to Arm 1 (Unasyn) or Arm 2 (ampicillin/gentamicin). She will be treated as per standard of care with tylenol, intravenous fluids, and her labor managed per physician discretion. From the time of diagnosis of chorioamnionitis until determination of treatment success or failure in the postpartum period, the patient will receive intravenous antibiotics per the protocol arm to which they have been assigned. If a patient has already been receiving ampicillin for GBS, the ampicillin will be discontinued when the study drugs are initiated. In arm 1, the study drugs will consist of Unasyn 3 grams intravenously every 6 hours, plus intravenous normal saline placebo dose every 8 hours. In arm 2, the study drugs will consist of gentamicin 1.5mg/kg intravenously every 8 hours plus ampicillin 2gm intravenously every 6 hours. For all patients, clindamycin will be given intravenously at the time of clamping of the umbilical cord in the event of a cesarean delivery, and continued as part of the antibiotic regimen as per standard of care for cesarean section in the setting of chorioamnionitis. With the exception of the saline placebo doses, both the Unasyn regimen and the ampicillin/gentamicin regimen are efficacious and widely utilized regimens for the treatment of intrapartum chorioamnionitis, and do not represent a deviation from standard of care. After delivery, if the patient experiences a treatment failure as defined below, her medical care will be managed at the discretion of the attending physician as per standard of care, and her antibiotic regimen will be unblinded. After delivery, prior to discharge from the hospital, the patient will be asked to answer a short questionnaire enquiring about side effects experienced during treatment for chorioamnionitis. The patient may receive a phone call within 14 days of delivery to assess whether she has received treatment for postpartum complications at an outside institution after discharge from the hospital.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Pregnant women in labor or undergoing induction of labor
2. Greater than or equal to 18 years of age
3. Diagnosed with chorioamnionitis as defined by maternal temperature > or = 38.0 degrees Centigrade plus at least one of the following: maternal tachycardia (heart rate >110), fetal tachycardia (fetal heart rate baseline >160), purulent amniotic fluid, uterine tenderness.

Exclusion Criteria:

1. Allergy or adverse reaction to penicillin or ampicillin, gentamicin, or sulbactam
2. Having received antibiotics for the treatment of preterm premature rupture of membranes or other condition within the last 7 days
3. Acute or chronic renal disease or insufficiency (creatinine >1.0)
4. Hearing loss
5. Major fetal congenital anomalies or intrauterine fetal demise
6. Neutropenia
7. HIV
8. Myasthenia gravis or other neuromuscular disorder

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Unasyn (ampicillin/sulbactam)	Drug: Unasyn; Unasyn 3 grams intravenously every 6 hours, plus intravenous normal saline placebo dose every 8 hours until 24 hours post delivery.
Active Comparator: Ampicillin/gentamicin	Drug: Ampicillin/gentamicin; Gentamicin 1.5mg/kg intravenously every 8 hours plus ampicillin 2 grams intravenously every 6 hours until 24 hours post delivery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Success Defined as Resolution of Fever by 24 Hours Postpartum	Proportion of patients in each arm experiencing treatment success defined as resolution of fever by 24 hours postpartum	Up to 24 hours after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Maternal Morbidity	Composite of maternal postpartum morbidity defined as any of the following outcomes: endometritis, clinical sepsis, pneumonia, blood transfusion or ileus.	Up to 6 weeks after delivery
Neonatal Clinical Sepsis (Early Onset)		Up to 6 weeks after delivery

Collaborators and Investigators

• Sponsor: Stanford University

Publications and helpful links

General Publications

• Greenberg, Mara et al. Comparison of ampicillin/sulbactam versus ampicillin/gentamicin for treatment of intrapartum chorioamnionitis: a randomized controlled trial. American Journal of Obstetrics & Gynecology , Volume 212 , Issue 1 , S145

Helpful Links

• Comparison of ampicillin/sulbactam versus ampicillin/gentamicin for treatment of intrapartum chorioamnionitis: a randomized controlled trial

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2009
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: April 7, 2009
• First Submitted That Met QC Criteria: April 8, 2009
• First Posted (Estimate): April 9, 2009

Study Record Updates

• Last Update Posted (Actual): May 18, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Fetal Diseases; Pregnancy Complications; Fetal Membranes, Premature Rupture; Obstetric Labor Complications; Placenta Diseases; Chorioamnionitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Ampicillin; Gentamicins
• Other Study ID Numbers: SU-03192009-2018; 15562 (Stanford University Research Compliance Office)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No