RCT of Postoperative Infections Following Caesarean Section Infections Following Caesarean Section

NCT02009098 | Withdrawn Phase 4 DMC

• 1 other identifier: 2012-002068-29
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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).

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• 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

Other Outcomes (1)

• Characteristics of the study population, which may affect the primary outcome "postoperative infections"

  participants will be followed for the duration of hospital stay, an expected average of 4 days

Study Arms (2)

præoperativ antibiotic

ACTIVE COMPARATOR

iv Cefuroxime 1,5g administered 15-60 minutes before incision

Drug: Cefuroxime

postoperativ antibiotic

ACTIVE COMPARATOR

iv Cefuroxime 1,5g administered after umbilical cord clamping

Drug: Cefuroxime

Interventions

Cefuroxime DRUG

iv Cefuroxime 1,5g administered 15-60 minutes before incision versus iv Cefuroxime 1,5g administered after umbilical cord clamping

Also known as: Cefuroxime "Fresenius Kabi"

postoperativ antibiotic; præoperativ antibiotic

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Odense University Hospital: lead
• Region of Southern Denmark: collaborator
• University of Southern Denmark: collaborator
• Hvidovre University Hospital: collaborator
• Esbjerg Hospital - University Hospital of Southern Denmark: collaborator

Study Sites (3)

Hospital of South West Jutland

Esbjerg, 6700, Denmark

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

Odense University Hospital

Odense, 5000, Denmark

Location

MeSH Terms

Conditions

Surgical Wound Infection; Endometritis; Wound Infection; Urinary Tract Infections

Interventions

Cefuroxime

Condition Hierarchy (Ancestors)

Infections; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pelvic Inflammatory Disease; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Uterine Diseases; Genital Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• 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 CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Study Record Dates

• First Submitted: May 5, 2013
• First Posted: December 11, 2013
• Study Start: October 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: June 1, 2016
• Last Updated: April 21, 2015

Record last verified: 2014-10

Locations

DK (3)