Pragmatic multicentre FActorial randomised controlled triaL testing measures to reduCe surgical site infection in lOw and middle income couNtries.

Surgical site infection (SSI) represents a major burden for patients, doctors, and health systems across all settings. SSI is the commonest postoperative complication worldwide and the commonest healthcare-associated infection in low and middle income countries (LMICs). SSIs cause pain, discomfort, disability, and increase the time taken to return to work. SSIs increase health costs and this can have a major impact on patients, communities, and providers in LMICs where personal income is low and patients may be required to pay for their own treatment. SSI has also been associated with one-third of postoperative deaths and accounts for 8% of all deaths caused by a nosocomial infection.

The GlobalSurg-2 cohort study captured data on 12539 patients undergoing abdominal surgery across 343 hospitals in 66 countries, with a primary outcome measure of SSI. The overall SSI rate was 12.3% (1538/12539), which more than doubled across high, middle, and low human development index (HDI) countries (9.4%, 14.0%, 23.2%, respectively, p<0.001). The overall SSI rate in LMICs was 16.3% (847/5200). After risk adjustment for patient, disease, operative, and hospital factors, patients in low-income countries remained at greater risk of SSI than those in high-income countries (adjusted OR 1.60, 95% confidence interval 1.05-2.37, p=0.030). The overall SSI rates in children and adults were similar (12.1% vs. 12.3%).

Improving surgical outcomes is a global health priority, highlighted by the Lancet Commission on Global Surgery. Recent World Health Organisation (WHO) guidelines made 29 recommendations for intraoperative and postoperative measures to prevent SSI, including global perspectives relevant to LMICs. Despite inclusion of strongly graded recommendations, there was little high quality evidence in support of most interventions. In addition, none of the evidence used was derived from resource limited settings, leading to uncertainty about implementation of measures in these settings. A randomised trial with the potential to evaluate multiple interventions would establish a high quality evidence base that will inform guidance, and influence revisions to the WHO Surgical Safety Checklist. The specific interventions to be tested in the trial were selected by a Delphi process from a long list of potential interventions based on the WHO guidelines.

Primary objective:

To assess whether either (1) 2% alcoholic chlorhexidine versus 10% povidone-iodine for skin preparation, or (2) triclosan-coated suture versus non-coated suture for fascial closure, can reduce surgical site infection at 30-days post-surgery for each of (i) clean-contaminated and (ii) contaminated or dirty abdominal surgery.

Secondary objectives:

       1.       To assess the impact of the interventions on secondary clinical outcomes up to 30 days post-surgery including: SSI at discharge, mortality, unplanned wound opening, re-operation, length of hospital stay, re-admission, and return to normal activities.

       2.       To assess the impact of the interventions on the resistance of organisms isolated from wound swabs to prophylactic antibiotics administered.

       3.       To explore the impact of the interventions on service delivery and additional costs to the secondary health service provider.

Primary outcome:

Primary outcome of the trial is Surgical Site Infection (SSI) at 30-days post-surgery.

The CDC (Centre for Disease Control) definitions will be used in FALCON to identify deep incisional or superficial incisional SSIs:

• The infection must occur within 30-days of the index operation

AND

• The infection must involve the skin, subcutaneous, muscular or fascial layers of the incision

AND

• The patient must have at least one of the following:
  • Purulent drainage from the wound
  • Organisms are detected from a wound swab
  • Wound opened spontaneously or by a clinician AND, at the surgical wound, the patient has at least one of: pain or tenderness; localised swelling; redness; heat; systemic fever (>38°C).
    • Diagnosis of SSI by a clinician or on imaging

AND

• The patient must have at least one of the following:
  • • Purulent drainage from the wound
    • Organisms are detected from a wound swab
    • Wound opened spontaneously or by a clinician AND, at the surgical wound, the patient has at least one of:
      • • • pain or tenderness
          • localised swelling
          • redness
          • heat
          • systemic fever (>38°C).
    • Diagnosis of SSI by a clinician or on imaging

Secondary outcomes:

 1.       SSI at discharge from hospital

2.       Mortality within 30-days post-surgery

3.       Unplanned wound opening within 30-days of surgery

4.       Re-operation for SSI within 30-days of surgery

5.       Length of hospital stay for index admission

6.       Readmission within 30 days of surgery

7.       Return to normal activities (e.g. work, school, or family duties) within 30-days

8.       Resistance of organisms detected from wound swabs to prophylactic antibiotics administered within 1 hour of incision

9.       The following health resource usage outcomes within 30-days will only be collected for adult patients (aged 18 years and above) at pre-selected centres:  length of stay in hospital; readmission to hospital; discharge from hospital with (i) pain killers, (ii) antibiotics, (iii) wound dressings; cost of post-operative visit with wound problem (i) to hospital, (ii) to a community doctor, (iii) to a nurse or other health worker, (iv) home visit by a nurse or other health worker

FALCON is a pragmatic, patient and outcome assessor blinded, 2×2 factorial, stratified, multi-centre randomised controlled trial, with an internal pilot, to evaluate measures to reduce SSI rates in patients undergoing surgery with an abdominal incision. Strata are defined according to the anticipated category of wound contamination: (1) clean-contaminated and (2) contaminated/dirty.

 

Patients (adults and children) undergoing surgery with abdominal incision of at least ≥5cm, with an anticipated (1) clean-contaminated or (2) contaminated/dirty wound. Participants undergoing emergency or elective, and open or laparoscopic surgery are eligible.

The FALCON trial has a 6-month internal pilot the aim of which is to assess:

• If recruitment to the randomised interventions is feasible
• Compliance with treatment allocation
• Patient retention and follow-up.

By the end of the pilot, at least 100 patients should be randomised from across five centres. The trial aims to randomise 5,480 patients in total.

Inclusion Criteria

• Patients with at least one abdominal incision that is ≥5cm (open or laparoscopic extraction site), with an anticipated clean-contaminated, contaminated or dirty surgical wound. Definitions and examples of contamination are given in Table 1.
• Patients undergoing emergency (surgery on an unplanned admission) or elective (surgery on a planned admission) operations.
• Any operative indication, including trauma surgery.
• Patient able and willing to provide written informed consent (signature or a fingerprint).
• Patients aged XX years and over. (This criteria is made country-specific. Each country decides the lower age limit for the trial. This is dependent on country-specific regulatory approvals. Age eligibility varies by country.)

Exclusion Criteria

• Patients with a documented or suspected allergy to iodine, shellfish, or chlorhexidine skin preparation solution.
• Patient unable to complete post-operative follow-up (i.e. will not be contactable after discharge).

This study is funded by the National Institute for Health Research (NIHR) Global Health Award (Grant Reference Number 16/136/79). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

If you are one of the FALCON sites and are open to recruitment you can randomised 24 hours a day, 7 days a week. This can be done either by phone or online. 

Telephone Randomisation - call +44 (0)1224 27 3661

You will need to know your centre/site ID code and enter this at the start of the call - this will be available from your local PI and their team, and also from the FALCON Trial Office.

Online Randomisation - visit https://w3.abdn.ac.uk/hsru/FALCON

You will need to login using your unique username, which can be obtained by contacting the FALCON Trial Office.