Treatment Utility of Postpartum Antibiotics in Chorioamnionitis (TUPAC)

To determine if prophylactic postpartum antibiotics are required post-cesarean delivery for pregnancies with treated chorioamnionitis.

Study Overview

• Status: Terminated
• Conditions: The Primary Outcome of This Study Will be the Rate of Endometritis
• Intervention / Treatment: Drug: Postpartum Antibiotics; Drug: No postpartum antibiotics

Detailed Description

Bacterial infection of the amniotic cavity, termed "chorioamnionitis", is a major cause of perinatal mortality and maternal morbidity. Early administration of broad-spectrum antibiotic therapy in the laboring patient with chorioamnionitis has both neonatal and maternal benefits. Less known is the ideal postpartum antibiotic regimen - or if postpartum antibiotics are even required at all - needed to decrease febrile morbidity. Current practice has seen a wide range of practice styles ranging from no treatment to antibiotic prophylaxis for up to 48 hours after delivery.

If antibiotics are prescribed, there is good evidence to support one additional dose of antibiotics as compared to 24 hour dosing to decrease the rate of endometritis. Less clear is whether antibiotics are required at all for the properly treated patient with chorioamnionitis who requires a cesarean delivery. One study comparing continued antibiotics versus no-treatment failed to show a difference in the rate of postpartum endometritis. The conclusion from this study was that continuation of preoperative clindamycin and gentamicin in the postoperative period did not reduce the risk of endometritis compared to a single preoperative dose however this study was terminated early due to failure to recruit their stated sample size.

Puerperal endometritis rates vary by mode of delivery but it is known that the rate is lower in vaginal deliveries as compared to cesarean delivery. The patient with chorioamnionitis that requires a cesarean delivery makes an excellent study target. Given the lack of studied protocols, there currently are many acceptable methods for treating the patient with chorioamnionitis. Our proposed study plans to evaluate the two most common methods of treatment to determine the most effective regimen. If post-delivery antibiotics do not show a benefit to these highest risk subjects, it is likely inferred that patients that undergo a vaginal delivery will not require antibiotics as well.

Specific Aims There is conflicting data regarding the necessity of post-delivery antibiotics for patients with chorioamnionitis who undergo cesarean delivery. The primary objective of this study is to determine if postpartum antibiotics are necessary for antepartum treated cases of chorioamnionitis in patients undergoing a cesarean section.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Barnes-jewish Hospital
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 50 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Clinical diagnosis of chorioamnionitis
• Undergoing cesarean section for delivery

Exclusion Criteria:

• Multiple gestations,
• Allergy to beta-lactam antibiotics
• Patients with estimated creatinine clearance (ClCr) less than 70 mL/min
• Maternal fever explained by etiology other than chorioamnionitis
• Inability to comply with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Postpartum Antibiotics; Patients will receive one additional dose of postpartum antibiotics (Clinda, Gentamicin)	Drug: Postpartum Antibiotics; Patients randomized into this arm will receive one additional dose of gentamicin (1.5 mg/kg) and clindamycin (900mg) in the postpartum setting.
Placebo Comparator: No postpartum antibiotics; No further postpartum antibiotics	Drug: No postpartum antibiotics; Patients randomized into this arm will not receive any postpartum antibiotics after delivery. They will be managed identically to the other arm in terms of chorioamnionitis (fever pre-delivery). The groups will be managed identically if endometritis (post-partum fever) develops.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Paricipants With Endometritis	Endometritis is defined as uterine infection and is diagnosed by maternal temp > 38.0C on two occasions over a 4 hour period or any temp > 39.0C after delivery > 12 hours after delivery. Endometritis will be managed per currently accepted endometritis protocol - (Amp 2 gQ6, Gentamicin 5 mg/kg q24, Clindamycin 900 mg q8).	7 days post-partum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Infection-related Complications	Infection related complications will include common complications attributed to infections there are not the primary outcome (endometritis). This will include infections of the wound and pelvic abscesses.	7 days post-partum
Duration of Hospital Stay After Cesarean Delivery	This is the duration of hospital stay (in days) after their cesarean delivery.	Up to 7 Days

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: St. Louis University
• Investigators: Principal Investigator: Anthony L Shanks, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Turnquest MA, How HY, Cook CR, O'Rourke TP, Cureton AC, Spinnato JA, Brown HL. Chorioamnionitis: is continuation of antibiotic therapy necessary after cesarean section? Am J Obstet Gynecol. 1998 Nov;179(5):1261-6. doi: 10.1016/s0002-9378(98)70143-7.
• Gibbs RS, Dinsmoor MJ, Newton ER, Ramamurthy RS. A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection. Obstet Gynecol. 1988 Dec;72(6):823-8. doi: 10.1097/00006250-198812000-00001.
• Sperling RS, Ramamurthy RS, Gibbs RS. A comparison of intrapartum versus immediate postpartum treatment of intra-amniotic infection. Obstet Gynecol. 1987 Dec;70(6):861-5.
• Gilstrap LC 3rd, Leveno KJ, Cox SM, Burris JS, Mashburn M, Rosenfeld CR. Intrapartum treatment of acute chorioamnionitis: impact on neonatal sepsis. Am J Obstet Gynecol. 1988 Sep;159(3):579-83. doi: 10.1016/s0002-9378(88)80012-7.
• Edwards RK, Duff P. Single additional dose postpartum therapy for women with chorioamnionitis. Obstet Gynecol. 2003 Nov;102(5 Pt 1):957-61. doi: 10.1016/s0029-7844(03)00863-9.
• Chapman SJ, Owen J. Randomized trial of single-dose versus multiple-dose cefotetan for the postpartum treatment of intrapartum chorioamnionitis. Am J Obstet Gynecol. 1997 Oct;177(4):831-4. doi: 10.1016/s0002-9378(97)70277-1.
• Duff P. Pathophysiology and management of postcesarean endomyometritis. Obstet Gynecol. 1986 Feb;67(2):269-76. doi: 10.1097/00006250-198602000-00021.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: April 23, 2012
• First Submitted That Met QC Criteria: April 24, 2012
• First Posted (Estimate): April 25, 2012

Study Record Updates

• Last Update Posted (Actual): June 19, 2018
• Last Update Submitted That Met QC Criteria: May 21, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Uterine Diseases; Adnexal Diseases; Fetal Diseases; Pregnancy Complications; Fetal Membranes, Premature Rupture; Obstetric Labor Complications; Placenta Diseases; Pelvic Inflammatory Disease; Chorioamnionitis; Endometritis; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: 09-0704