Intrapartum Fever: Antibiotics Versus no Treatment
Primary Purpose
Chorioamnionitis, Intrapartum Fever, Intra-amniotic Infection
Status
Withdrawn
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Standard Antibiotic Treatment
No Antibiotic Treatment
Sponsored by
About this trial
This is an interventional diagnostic trial for Chorioamnionitis
Eligibility Criteria
Inclusion Criteria:
- Pregnant women between 34-42 weeks gestation
- Singleton fetus
- Admitted for labor management & develops a fever of 100.4 F or greater
Exclusion Criteria:
- Known fetal anomaly
- Other indication for intrapartum antibiotics (endocarditis prophylaxis, other known maternal infection)
Sites / Locations
- University of Utah, Department of Obstetrics & Gynecology
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Standard Antibiotic Treatment
No Antibiotic Treatment
Arm Description
Standard antibiotic treatment provided to patient. Placenta submitted for pathologic exam. Maternal and neonatal outcomes collected.
No Antibiotic treatment given. Placenta submitted for pathologic exam. Maternal and neonatal outcomes collected.
Outcomes
Primary Outcome Measures
Neonatal antibiotic treatment as recommended by the EONS (Early Onset Neonatal Sepsis) calculator.
All newborns will have a screening assessment including physical exam and vital signs, and this data along with maternal and delivery data is entered into the Kaiser Permanente Early Onset Neonatal Sepsis (EONS) calculator. The EONS calculator estimates the risk of sepsis and recommends observation, additional evaluation, or empiric antibiotic treatment.
Secondary Outcome Measures
Positive blood culture
For infants who have a blood culture obtained by recommendation of the EONS calculator, the presence of significant bacterial growth will be considered a positive culture.
Need for NICU admission
Admission of the infant to the Newborn Intensive Care Unit
Newborn length of stay
Days hospitalized after birth
Maternal endometritis
The diagnosis of endometritis made by the patient's OB provider requiring treatment with antibiotics.
Maternal length of stay
Days hospitalized after delivery
Patient satisfaction
Satisfaction with maternal and newborn care using a standardized survey administered by phone at 6-8 weeks after delivery
Cost
The hospital charges for mother and infant
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03168178
Brief Title
Intrapartum Fever: Antibiotics Versus no Treatment
Official Title
A Randomized Trial in Intrapartum Fever Of No Antibiotics for Low-risk Women (RATIONAL)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Withdrawn
Why Stopped
Participant enrollment was much more challenging than anticipated.
Study Start Date
June 8, 2017 (Actual)
Primary Completion Date
July 26, 2018 (Actual)
Study Completion Date
July 26, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Utah
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine whether antibiotics can be safely avoided in women who develop a fever during labor. Because investigators have no accurate tests to determine whether women who develop fever during labor have intra-amniotic infection, antibiotics are often used to prevent spread of infection to the fetus.
Detailed Description
A fever > 100.4 F during labor (intrapartum fever) complicates up to 14% of term deliveries, and is commonly considered a sign of intrauterine infection. Despite studies showing that most causes of maternal intrapartum fever are non-infectious, intrapartum fever often prompts the diagnosis of chorioamnionitis/intrauterine infection, or what is now known as 'triple I' (intra-amniotic infection or inflammation). Diagnosis of triple I is primarily based on clinical findings such as maternal fever, maternal leukocytosis, uterine tenderness, foul-smelling or purulent amniotic fluid, and fetal tachycardia. A minimum of two of these criteria for diagnosis, although this distinction is somewhat artificial as fetal tachycardia is highly associated with maternal fever. The poor performance of clinical signs and lack of effective biomarkers to identify neonatal infection results in over treatment of both mothers and infants.
Avoiding antibiotic use in mothers and infants is desirable in order to avoid unnecessary separation after birth, decreasing cost and interventions in newborns, and to avoid altering the infant's microbiome (the bacteria newborns carry on their skin, mucosal membranes, and in their gut at the time of birth). Infants with altered microbiomes may be at risk for skin, pulmonary, and gastrointestinal disorders. The investigators in this trial are randomizing women with fever during labor who are felt to be a low risk for true infection to antibiotic treatment compared to no antibiotics in order to determine if antibiotics can be safely avoided for these women and their infants.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chorioamnionitis, Intrapartum Fever, Intra-amniotic Infection
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Low risk women will be randomized to standard antibiotic treatment versus no antiobiotics.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Standard Antibiotic Treatment
Arm Type
Active Comparator
Arm Description
Standard antibiotic treatment provided to patient. Placenta submitted for pathologic exam. Maternal and neonatal outcomes collected.
Arm Title
No Antibiotic Treatment
Arm Type
Experimental
Arm Description
No Antibiotic treatment given. Placenta submitted for pathologic exam. Maternal and neonatal outcomes collected.
Intervention Type
Drug
Intervention Name(s)
Standard Antibiotic Treatment
Intervention Description
Participants randomized to this intervention will receive standard antibiotic treatment.
The placenta will be submitted for pathologic exam after delivery and investigators will collect maternal and neonatal outcomes
Intervention Type
Other
Intervention Name(s)
No Antibiotic Treatment
Intervention Description
Participant randomized to this arm of the study will not receive antibiotics. The placenta will be submitted for pathologic exam after delivery and investigators will collect maternal and neonatal outcomes
Primary Outcome Measure Information:
Title
Neonatal antibiotic treatment as recommended by the EONS (Early Onset Neonatal Sepsis) calculator.
Description
All newborns will have a screening assessment including physical exam and vital signs, and this data along with maternal and delivery data is entered into the Kaiser Permanente Early Onset Neonatal Sepsis (EONS) calculator. The EONS calculator estimates the risk of sepsis and recommends observation, additional evaluation, or empiric antibiotic treatment.
Time Frame
Within 2 hours of delivery
Secondary Outcome Measure Information:
Title
Positive blood culture
Description
For infants who have a blood culture obtained by recommendation of the EONS calculator, the presence of significant bacterial growth will be considered a positive culture.
Time Frame
Up to 4 days after birth
Title
Need for NICU admission
Description
Admission of the infant to the Newborn Intensive Care Unit
Time Frame
Up to 4 weeks after birth
Title
Newborn length of stay
Description
Days hospitalized after birth
Time Frame
Up to 4 weeks after birth
Title
Maternal endometritis
Description
The diagnosis of endometritis made by the patient's OB provider requiring treatment with antibiotics.
Time Frame
Up to 4 weeks after birth
Title
Maternal length of stay
Description
Days hospitalized after delivery
Time Frame
Up to 4 weeks after birth
Title
Patient satisfaction
Description
Satisfaction with maternal and newborn care using a standardized survey administered by phone at 6-8 weeks after delivery
Time Frame
6-8 weeks after delivery
Title
Cost
Description
The hospital charges for mother and infant
Time Frame
Up to 4 weeks after birth
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pregnant women between 34-42 weeks gestation
Singleton fetus
Admitted for labor management & develops a fever of 100.4 F or greater
Exclusion Criteria:
Known fetal anomaly
Other indication for intrapartum antibiotics (endocarditis prophylaxis, other known maternal infection)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heather Campbell, MD
Organizational Affiliation
University of Utah
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Utah, Department of Obstetrics & Gynecology
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
12548228
Citation
Smulian JC, Bhandari V, Vintzileos AM, Shen-Schwarz S, Quashie C, Lai-Lin YL, Ananth CV. Intrapartum fever at term: serum and histologic markers of inflammation. Am J Obstet Gynecol. 2003 Jan;188(1):269-74. doi: 10.1067/mob.2003.11.
Results Reference
background
PubMed Identifier
10576190
Citation
Smulian JC, Shen-Schwarz S, Vintzileos AM, Lake MF, Ananth CV. Clinical chorioamnionitis and histologic placental inflammation. Obstet Gynecol. 1999 Dec;94(6):1000-5. doi: 10.1016/s0029-7844(99)00416-0.
Results Reference
background
PubMed Identifier
22412842
Citation
Roberts DJ, Celi AC, Riley LE, Onderdonk AB, Boyd TK, Johnson LC, Lieberman E. Acute histologic chorioamnionitis at term: nearly always noninfectious. PLoS One. 2012;7(3):e31819. doi: 10.1371/journal.pone.0031819. Epub 2012 Mar 7.
Results Reference
background
PubMed Identifier
22778303
Citation
Taylor JA, Opel DJ. Choriophobia: a 1-act play. Pediatrics. 2012 Aug;130(2):342-6. doi: 10.1542/peds.2012-0106. Epub 2012 Jul 9.
Results Reference
background
PubMed Identifier
24366992
Citation
Escobar GJ, Puopolo KM, Wi S, Turk BJ, Kuzniewicz MW, Walsh EM, Newman TB, Zupancic J, Lieberman E, Draper D. Stratification of risk of early-onset sepsis in newborns >/= 34 weeks' gestation. Pediatrics. 2014 Jan;133(1):30-6. doi: 10.1542/peds.2013-1689. Epub 2013 Dec 23.
Results Reference
background
PubMed Identifier
24772410
Citation
Cuna A, Hakima L, Tseng YA, Fornier B, Islam S, Quintos-Alagheband ML, Khullar P, Weinberger B, Hanna N. Clinical dilemma of positive histologic chorioamnionitis in term newborn. Front Pediatr. 2014 Apr 4;2:27. doi: 10.3389/fped.2014.00027. eCollection 2014.
Results Reference
background
PubMed Identifier
22901952
Citation
Evers AC, Nijhuis L, Koster MP, Bont LJ, Visser GH. Intrapartum fever at term: diagnostic markers to individualize the risk of fetal infection: a review. Obstet Gynecol Surv. 2012 Mar;67(3):187-200. doi: 10.1097/OGX.0b013e31824bb5f1.
Results Reference
background
PubMed Identifier
15663581
Citation
Buhimschi IA, Christner R, Buhimschi CS. Proteomic biomarker analysis of amniotic fluid for identification of intra-amniotic inflammation. BJOG. 2005 Feb;112(2):173-81. doi: 10.1111/j.1471-0528.2004.00340.x.
Results Reference
background
PubMed Identifier
21518717
Citation
Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, Bizzarro MJ, Goldberg RN, Frantz ID 3rd, Hale EC, Shankaran S, Kennedy K, Carlo WA, Watterberg KL, Bell EF, Walsh MC, Schibler K, Laptook AR, Shane AL, Schrag SJ, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics. 2011 May;127(5):817-26. doi: 10.1542/peds.2010-2217. Epub 2011 Apr 25. Erratum In: Pediatrics. 2011 Aug;128(2):390.
Results Reference
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PubMed Identifier
20974782
Citation
Newman TB, Puopolo KM, Wi S, Draper D, Escobar GJ. Interpreting complete blood counts soon after birth in newborns at risk for sepsis. Pediatrics. 2010 Nov;126(5):903-9. doi: 10.1542/peds.2010-0935. Epub 2010 Oct 25.
Results Reference
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Intrapartum Fever: Antibiotics Versus no Treatment
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