Intrapartum Fever: Antibiotics Versus no Treatment

Chorioamnionitis Clinical Trial

Official title:

A Randomized Trial in Intrapartum Fever Of No Antibiotics for Low-risk Women (RATIONAL)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03168178
• Other study ID #: 91955
• Status: Withdrawn
• Phase: Phase 4
• Start date: June 8, 2017
• Est. completion date: July 26, 2018

Study information

• Verified date: October 2018
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 26, 2018
• Est. primary completion date: July 26, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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)

Related Conditions & MeSH terms

• Chorioamnionitis
• Fever
• Intra-amniotic Infection
• Intrapartum Fever

Intervention

Drug:
• Standard Antibiotic Treatment
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

Other:
• No Antibiotic Treatment
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

Locations

Country	Name	City	State
United States	University of Utah, Department of Obstetrics & Gynecology	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View 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. — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View 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. — View Citation

Stoll BJ, Hansen NI, Sánchez 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Within 2 hours of delivery
Secondary	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.	Up to 4 days after birth
Secondary	Need for NICU admission	Admission of the infant to the Newborn Intensive Care Unit	Up to 4 weeks after birth
Secondary	Newborn length of stay	Days hospitalized after birth	Up to 4 weeks after birth
Secondary	Maternal endometritis	The diagnosis of endometritis made by the patient's OB provider requiring treatment with antibiotics.	Up to 4 weeks after birth
Secondary	Maternal length of stay	Days hospitalized after delivery	Up to 4 weeks after birth
Secondary	Patient satisfaction	Satisfaction with maternal and newborn care using a standardized survey administered by phone at 6-8 weeks after delivery	6-8 weeks after delivery
Secondary	Cost	The hospital charges for mother and infant	Up to 4 weeks after birth