FALCON Trial Testing Measures to Reduce Surgical Site Infection

Study Overview
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Brief Summary
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FALCON is a Pragmatic multi-centre trial testing measures to reduce superficial or deep skin infection following abdominal surgery in low and middle income countries. The trial will recruit patients undergoing abdominal surgery. Recruited participants will be randomly assigned to four arms to receive different combinations of skin preparation and sutures for would closure: A. In this arm surgeon will use 2% alcoholic chlorhexidine for skin cleansing and non-coated suture for wound closure; B. In this arm surgeon will use 2% alcoholic chlorhexidine for skin cleansing and triclosan coated suture for wound closure; C. In this arm surgeon will use for operation 10% aqueous povidone-iodine for skin cleansing and non-coated suture for wound closure; D. In this arm surgeon will use 10% aqueous povidone-iodine for skin cleansing and triclosan-coated suture.

Detailed Description
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FALCON is a pragmatic, blinded (patient and outcome assessor), 2x2 factorial, stratified, multi-centre randomised controlled trial, with an internal pilot, to evaluate measures to reduce Surgical Site Infection (SSI) rates in patients undergoing surgery with an abdominal incision. 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 (3). SSIs increase healthcare costs in all health settings. Whilst there is no direct data on the costs of SSI in LMICs, within the UK National Health Service, SSIs cost approximately £3500 per patient and £700 million per year in total. The impact of increased healthcare costs on patients, communities, and providers can be major 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 hospital acquired infection. Strata in FALCON trial are defined according to the anticipated category of wound contamination: (1) clean-contaminated and (2) contaminated/dirty. Eligible patients will be randomised at the level of the individual in a 1:1:1:1 ratio between: A. 2% alcoholic chlorhexidine and non-coated suture B. 2% alcoholic chlorhexidine and triclosan-coated suture C. 10% aqueous povidone-iodine and non-coated suture D. 10% aqueous povidone-iodine and triclosan-coated suture. Participant will be recruited from hospitals in Low and Middle Income Countries (LMICs). Participants who is undergoing abdominal surgery with an anticipated clean-contaminated, contaminated or dirty surgical wound will be selected to enter the trial. The 6 month internal pilot will assess the feasibility of recruitment, compliance with treatment allocation and patient retention and follow-up rates. The main RCT will recruit 5480 participants.

Official Title
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Pragmatic Multicentre FActorial Randomised Controlled triaL Testing Measures to reduCe Surgical Site Infection in lOw and Middle Income couNtries

Conditions
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Abdominal Surgery, Surgical Site Infection

Intervention / Treatment
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* Drug: 2% chlorhexidine + non-coated suture
* Drug: 2% chlorhexidine + coated suture
* Drug: 10%povidone-iodine + non-coated suture
* Drug: 10%povidone-iodine + coated suture


Participation Criteria
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Eligibility Criteria
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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. 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). Paediatric and adult patients. 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 will vary 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).

Ages Eligible for Study
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Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: FALCON 2x2 factorial trial with strata: (1) clean-contaminated and (2) contaminated/dirty. Eligible patients will be randomised at the level of the individual in a 1:1:1:1 ratio between: A. 2% alcoholic chlorhexidine and non-coated suture B. 2% alcoholic chlorhexidine and triclosan-coated suture C. 10% aqueous povidone-iodine and non-coated suture D. 10% aqueous povidone-iodine and triclosan-coated suture
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2%chlorhexidine + non-coated suture<br>2%alcoholic chlorhexidine + non-coated suture. Intervention: skin preparation with 2%alcoholic chlorhexidine in combination with non-coated suture for abdominal fascial closure. | Drug: 2% chlorhexidine + non-coated suture<br>* Interventions: 2% alcoholic chlorhexidine non-coated suture<br>|
| Active Comparator: 2%chlorhexidine + coated suture<br>2%alcoholic chlorhexidine + triclosan-coated suture. Intervention: skin preparation with 2%alcoholic chlorhexidine in combination with triclosan-coated suture for abdominal fascia closure. | Drug: 2% chlorhexidine + coated suture<br>* Interventions: 2% alcoholic chlorhexidine triclosan coated suture<br>|
| Active Comparator: 10% povidone-iodine + non-coated suture<br>10% povidone-iodine and non-coated suture. Intervention: skin preparation with 10% povidone-iodine in combination with non-coated suture for abdominal fascial closure. | Drug: 10%povidone-iodine + non-coated suture<br>* Interventions: 10% povidone-iodine non-coated suture non-coated suture<br>|
| Active Comparator: 10%povidone-iodine + coated suture<br>10%povidone-iodine/triclosan-coated suture. Intervention: skin preparation with 10% povidone-iodine in combination with triclosan-coated suture for abdominal fascial closure. | Drug: 10%povidone-iodine + coated suture<br>* Interventions: 10% povidone-iodine triclosan coated suture<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical site infection (SSI) | Deep incisional or superficial incisional SSI which must occur within 30 days of the index operation. The infection must involve the skin, subcutaneous, muscular or fascial layers of the incision. Patient must at least have one of the following: (1) purulent discharge from wound; (2) organisms detected from wound swab; (3) 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); (4) Diagnosis of SSI by a clinician or on imaging. | At 30-days post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physiological parameter - SSI at discharge from hospital | Deep incisional or superficial incisional SSI. The infection must involve the skin, subcutaneous, muscular or fascial layers of the incision and the patient must have one of the following: (1) purulent discharge from wound; (2) organisms detected from wound swab; (3) 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); (4) Diagnosis of SSI by a clinician or on imaging. | Within 30-days post surgery from index operation | 
| Mortality - patient mortality status | Mortality within 30-days post surgery | Within 30-days post surgery from index operation | 
| Physiological parameter - Unplanned wound opening | Whether an unplanned wound opening has occurred at abdominal surgical site within 30-days post surgery, spontaneously opened or by clinician | Within 30-days post surgery from index operation | 
| Re-operation for SSI | Re-operation for SSI within 30-days post surgery | Within 30-days post surgery from index operation | 
| Length of hospital stay for index admission | Length of hospital stay for index admission will be collected and will measure time from surgery to time of discharge. | Within 30-days post surgery from index operation | 
| Participant's Readmission | Whether patient readmitted within 30-days post surgery | Within 30-days post surgery from index operation | 
| Questionnaire - return to normal activities | Return to normal activities (e.g. work, school, or family duties) ascertained by trial specific questionnaire | Within 30-days post surgery from index operation | 
| Resistance of organisms | Resistance of organisms detected from wound swabs to prophylactic antibiotics administered within 1 hour of incision | Within 30-days post surgery from index operation | 
| Questionnaire - Health resource usage | Health resource usage within 30-days post surgery ascertained by trial specific questionnaire | Within 30-days post surgery. Health resource usage will only be collected for adult patients (aged 18 and above) at pre-selected centres. This will include costs of post-operative visits to various healthcare professionals. |