RCT of Postoperative Infections Following Caesarean Section Infections Following Caesarean Section (APIPICS)

Antibiotic Prophylaxis and Intervention for Postpartum Infections Following Caesarean Section

Background Women undergoing Caesarean Section (CS) have an increased risk of postpartum infections compared to women undergoing vaginal delivery. In Denmark the incidence of post-CS infections is 7-10%. The most common infections are endometritis, Urinary tract infections (UTI) and wound infections (WI).

Prophylactic antibiotics are effective in preventing postoperative infections and national guidelines recommend that antibiotics should be administered as a single dose immediately before surgical incision. CS is an exception to this pre-incision administration approach. National guidelines recommend administration of antibiotics after umbilical cord clamping to avoid exposure of the child to antibiotics before birth. Recent studies of antibiotic prophylaxis for CS suggest that prophylactic antibiotics administered before incision compared to after umbilical cord clamping may reduce post-CS infections by up to 50%. Two Cochrane reviews from 2012 criticize these types of studies for lack of data for outcomes on the baby and on late infection in the mother.

This study is a double-blinded randomized controlled trial with a concurrent Health Economic Assessment. The study will examine the effect of change in timing of prophylactic antibiotics on the rate of post-CS infections (endometritis, UTI and WI). The study will be performed at the obstetric departments at Odense University Hospital (OUH), Hvidovre Hospital (HH) and Hospital South West Jutland (HSWJ) in collaboration with the Department of Clinical Microbiology, OUH, to ensure that the most appropriate antibiotic regime is used. Furthermore, collaboration with a neonatologist will ensure appropriate assessment of neonatal outcome.

The investigators plan to enroll the first patient at OUH February 2013. HH and HSWJ will follow with a couple of months delay. The inclusion period is scheduled to last until the investigators have 2844 participants, who have answered the questionnaire. The investigators expect to complete the inclusion period in October 2014 (last patient last visit, LPLV). Microbiological analyzes and data processing is expected to be completed one year after the LPLV. The study population is all women delivering a child by CS during the project period, at Department of Gynaecology and Obstetrics of OUH, HH and HSWJ.

Objective: Investigate whether and by how much antibiotics administered 15-60 minutes before incision versus after umbilical cord clamping reduces the rate of postpartum infections in a Danish population of women undergoing CS.

Hypothesis: Antibiotics administered pre-incision will result in fewer postoperative infections than antibiotics administered after the umbilical cord is cut.

Hypothesis: Antibiotics administered before incision are cost-effective, compared to administration after umbilical cord clamping, measured by post-CS infection and as cost per Quality Adjusted Life Year (QALY).

Study Overview

• Status: Withdrawn
• Conditions: Postoperative Infection
• Intervention / Treatment: Drug: Cefuroxime

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Esbjerg, Denmark, 6700
    • Hospital of South West Jutland
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

All women delivering a child by CS at term, at Odense University Hospital, Hvidovre Hospital or Hospital of South West Jutland, Denmark, will be included in the study. Informed consent will be obtained during pregnancy.

Inclusion Criteria:

• Age ≥ 18 year
• Women, who can read and understand Danish
• A gestational age ≥ completed 28 weeks of gestation
• Rupture of membranes and active labour (uterine contractions) is allowed.

Exclusion Criteria:

• Hypersensitivity to cefuroxime or to any other cephalosporin antibiotics
• Previous immediate and/or severe hypersensitivity reaction to penicillin or any other beta-lactam antibiotic.

• Systemic exposure to any antibiotic agent within 1 week before delivery

  _ Antibiotic indicated due to PROM, fever or other indications at the time of caesarean section.

• Women being immunologically incompetent (e.g. HIV positive)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: præoperativ antibiotic; iv Cefuroxime 1,5g administered 15-60 minutes before incision	Drug: Cefuroxime; iv Cefuroxime 1,5g administered 15-60 minutes before incision versus iv Cefuroxime 1,5g administered after umbilical cord clamping; Other Names: Cefuroxime "Fresenius Kabi"
Active Comparator: postoperativ antibiotic; iv Cefuroxime 1,5g administered after umbilical cord clamping	Drug: Cefuroxime; iv Cefuroxime 1,5g administered 15-60 minutes before incision versus iv Cefuroxime 1,5g administered after umbilical cord clamping; Other Names: Cefuroxime "Fresenius Kabi"

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Women: The incidence of post-CS infection (endometritis, urinary tract infections, and wound infections)	To be able to collect information about symptoms of infection after discharge a self-administered questionnaire will be sent to all participants within 30 days post-CS. Furthermore data on postoperative infections, recorded by diagnoses codes or surgical procedures, will be obtained from the Danish National Patient Registry.	within the first 30 days after surgery
Infant: admission to special care unit		participants will be followed for the duration of hospital stay, an expected average of 4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Women: length of the primary and any secondary hospitalization		within the first 30 days after Caesarean Section
Women: readmissions to hospital/contact to the general practitioner on suspicion of infection after Caesarean Section		within the first 30 days after Caesarean Section
Women: antibiotic treatment on suspicion of infection after Caesarean Section		within the first 30 days after Caesarean Section
Infant: use of antifungal treatment against oral thrush		participants will be followed for the duration of hospital stay, an expected average of 4 days
Infant: necrotizing enterocolitis		participants will be followed for the duration of hospital stay, an expected average of 4 days
Infant: antibiotic treatment during hospital stay		participants will be followed for the duration of hospital stay, an expected average of 4 days
Infant: the need for intensive care treatment and length of stay in hospital		participants will be followed for the duration of hospital stay, an expected average of 4 days
Infant: Neonatal sepsis	Neonatal sepsis, Neonatal sepsis workup	participants will be followed for the duration of hospital stay, an expected average of 4 days
Women: Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Adverse reactions/events registered during hospitalization (complications, examinations, treatments, antibiotic use)	participants will be followed for the duration of hospital stay, an expected average of 4 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characteristics of the study population, which may affect the primary outcome "postoperative infections"	Date of admission, Date of birth, Birthplace, Date of discharges. Ethnicity, Maternal age, height and prepregnancy weight, Parity, Multiple gestations, Gravidity, Prior caesareans, Prior abdominal surgery, Drug/alcohol abuse, Diabetes mellitus, Preeclampsia, Smoking status, self-reported, Urine track infection (before birth). Presence of labor, Length of labor, Preterm labor, Rupture of membranes, Length of rupture of membranes, Number of vaginal examinations, Use of internal monitoring, Meconium, Use of antenatal steroids, cervical dilators, vacuum, amnioinfusion, extraamniotic saline infusion. Type of section, Anaesthesia type, Uterine incision type, Uterine closure layers, Uterine incision extensions, Need for transfusion, Intraoperative blood loss, Time of day, Operative time, Deviation from the standard surgical procedure. Birth weight (gram), Gestational age (week	participants will be followed for the duration of hospital stay, an expected average of 4 days

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: Hvidovre University Hospital; University of Southern Denmark; Region of Southern Denmark; Hospital of South West Jutland
• Investigators: Study Chair: Jan Stener Joergensen, MD, PhD, Odense University Hospital, department of Gynaecology and Obstetrics, University of Southern Denmark, Faculty of Health Sciences, institute of Clinical Research, research unit, department of Gynaecology and Obstetrics

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): October 1, 2015
• Study Completion (Anticipated): June 1, 2016

Study Registration Dates

• First Submitted: May 5, 2013
• First Submitted That Met QC Criteria: December 6, 2013
• First Posted (Estimate): December 11, 2013

Study Record Updates

• Last Update Posted (Estimate): April 21, 2015
• Last Update Submitted That Met QC Criteria: April 20, 2015
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; urinary tract infections; antibiotics; prophylactic antibiotics; surgical site infections; preoperative; Caesarean Section; Antibiotic Prophylaxis; intraoperative; timing; wound infections; infectious morbidity; endometritis; neonatal antibiotics exposure
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Anti-Infective Agents; Anti-Bacterial Agents; Cefuroxime; Cefuroxime axetil
• Other Study ID Numbers: 2012-002068-29 (EUDRACT_NUMBER)