Clinical trial NCT02009098: RCT of Postoperative Infections Following Caesarean Section Infections Following Caesarean Section
Official title: Antibiotic Prophylaxis and Intervention for Postpartum Infections Following Caesarean Section
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Postoperative Infection
Keywords: Randomized Controlled Trial
Caesarean Section
preoperative
intraoperative
prophylactic antibiotics
antibiotics
timing
surgical site infections
endometritis
wound infections
urinary tract infections
infectious morbidity
neonatal antibiotics exposure
Antibiotic Prophylaxis
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Region of Southern Denmark
name: University of Southern Denmark
name: Hvidovre University Hospital
name: Esbjerg Hospital - University Hospital of Southern Denmark
First posted: 2013-12-11
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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)

Primary outcomes:
measure: Women: The incidence of post-CS infection (endometritis, urinary tract infections, and wound infections)
timeFrame: within the first 30 days after surgery
measure: Infant: admission to special care unit
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 4 days
Secondary outcomes:
measure: Women: length of the primary and any secondary hospitalization
timeFrame: within the first 30 days after Caesarean Section
measure: Women: readmissions to hospital/contact to the general practitioner on suspicion of infection after Caesarean Section
timeFrame: within the first 30 days after Caesarean Section
measure: Women: antibiotic treatment on suspicion of infection after Caesarean Section
timeFrame: within the first 30 days after Caesarean Section
measure: Infant: use of antifungal treatment against oral thrush
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 4 days
measure: Infant: necrotizing enterocolitis
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 4 days
measure: Infant: antibiotic treatment during hospital stay
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 4 days
measure: Infant: the need for intensive care treatment and length of stay in hospital
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 4 days
measure: Infant: Neonatal sepsis
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 4 days
measure: Women: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 4 days
Other outcomes:
measure: Characteristics of the study population, which may affect the primary outcome "postoperative infections"
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 4 days
Locations:
city: Esbjerg
country: Denmark
facility: Hospital of South West Jutland
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: 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
name: Jan Stener Joergensen, MD, PhD
role: STUDY_CHAIR
References: