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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Chorioamnionitis	Drug: Unasyn; Drug: Ampicillin/gentamicin	Phase 2; Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	92 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Comparison of Ampicillin / Sulbactam vs. Ampicillin / Gentamicin for Treatment of Intrapartum Chorioamnionitis: a Randomized Controlled Trial
Study Start Date :	May 2009
Actual Primary Completion Date :	September 2014
Estimated Study Completion Date :	November 2017

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Treatment Success Defined as Resolution of Fever by 24 Hours Postpartum [ Time Frame: Up to 24 hours after delivery ]
   Proportion of patients in each arm experiencing treatment success defined as resolution of fever by 24 hours postpartum

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 55 Years (Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

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

Sponsors and Collaborators

Stanford University

Investigators

Principal Investigator:	Natali Aziz, MD	Stanford University

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

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

Publications of Results:

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

Responsible Party:	Natali Aziz, Clinical Assistant Professor, Stanford University
ClinicalTrials.gov Identifier:	NCT00879190 History of Changes
Other Study ID Numbers:	SU-03192009-2018; 15562 ( Other Identifier: Stanford University Research Compliance Office )
First Posted:	April 9, 2009
Results First Posted:	March 15, 2017
Last Update Posted:	May 30, 2017
Last Verified:	April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Additional relevant MeSH terms:

Chorioamnionitis; Fetal Diseases; Pregnancy Complications; Fetal Membranes, Premature Rupture; Obstetric Labor Complications; Placenta Diseases; Gentamicins; Ampicillin	Sulbactam; Sultamicillin; Anti-Bacterial Agents; Anti-Infective Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; beta-Lactamase Inhibitors