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

Condition(s) targeted: Chorioamnionitis

Intervention: Unasyn (Drug); Ampicillin/gentamicin (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: Stanford University

Official(s) and/or principal investigator(s):
Natali Aziz MD, Principal Investigator, Affiliation: Stanford University

Overall contact:
Mara Greenberg, MD, Phone: (415) 867-2051, Email: mgreenberg@yahoo.com

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Proportion of patients in each arm experiencing treatment failure as indicated by resolution of maternal infection

Secondary outcome:

Maternal adverse effects including side effects, labor abnormalities, type of delivery, blood loss, post partum infectious complication.

Neonatal adverse outcomes.

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.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Female.

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

Mara Greenberg, MD, Phone: (415) 867-2051, Email: mgreenberg@yahoo.com

Stanford University School of Medicine, Stanford, California 94305, United States; Recruiting
Mara Greenberg, MD, Phone: 415-867-2051, Email: mgreenberg@yahoo.com
Mara Greenberg, Sub-Investigator
Natali Aziz MD, Principal Investigator
Yasser Yehia El-Sayed, Sub-Investigator
William E Benitz, Sub-Investigator
Maurice L Druzin, Sub-Investigator

Starting date: May 2009
Last updated: June 13, 2011