The Amputation Surgical Site Infection Trial (ASSIT) (ASSIT)

A Randomised Control Trial to Determine Whether a 5 Day Course of Antibiotics is More Clinically and Cost Effective Than a 24 Hour Prophylactic Course for the Prevention of Surgical Site Infection Following Lower Limb Amputation

• Lower limb amputations are performed usually as a last resort in patients with acute and chronic limb ischaemia (CLI) caused by vascular disease, poorly controlled diabetes or, infection.
• In the period 2003-2008 there were approximately 5,000 amputations per year in the UK.
• The Centre for Disease Control defines a Surgical Site Infection (SSI) as an infection within 30 days of an operation or up to one year if an implant is left in place and the infection is related to an operative procedure.
• Figures from the Surgical Site Infection Surveillance reported that the highest rate of surgical site infection was reported in association with lower limb amputation at 13.1%.
• There is a clear under-representation and the infection rate within our institution is approximately 25% which reflects the infection rate reported in a recent trial by Sadat et al (22.5%)
• Prevention of surgical site infections is of paramount importance to patients, healthcare providers and policy-makers, as they impact on morbidity and mortality and have significant time and cost implications.
• Currently there is NO CONSENSUS as to what the best practice is towards antibiotic administration in such patients. From a questionnaire-based audit we performed including vascular departments across the entire country, practice varies in both course duration (single dose → 5 days antibiotic course) as well as choice of antibiotics.
• The guideline at our institution suggests the 5-day course of antibiotic prophylaxis. The course duration varies depending on the clinical picture as well as microbiology results and recommendations.
• There are no randomised control trials that have investigated this aspect of patient care. We have set up one such trial and through it, we are looking to establish a standard practice which will hopefully be as beneficial as possible to the patient but also cost-effective for NHS.

Study Overview

• Status: Completed
• Conditions: Wound Infection; Amputation Wound
• Intervention / Treatment: Drug: Co-amoxiclav; Drug: Iodine; Drug: Metronidazole; Drug: Chlorhexidine; Drug: Teicoplanin; Drug: Clindamycin

Detailed Description

As above

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Hull, United Kingdom, HU3 2JZ
    • Hull Royal Infirmary

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adults ≥18 yrs undergoing lower limb amputations who are able to consent to the trial.
2. Able to understand the Patient Information Sheet and capable and willing to give informed consent and follow the protocol requirements (including attending all follow-up visits)

Exclusion Criteria:

1. Allergies to chlorhexidine/ alcohol/ iodophors
2. Inability to give informed consent
3. Patients who are admitted to hospital with severe sepsis secondary to gas gangrene requiring multiple operations and admission to Intensive Care Unit.
4. Aged under 18 years at the time of recruitment
5. Use of investigational drug/device therapy within preceding 4 weeks that may interfere with this study.
6. Toe amputations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 24 hour antibiotic course; 24 hours of the stated antibiotics administered intravenously (Augmentin and metronidazole. Teicoplanin and or gentamicin will be used if penicillin allergic and state of renal function)	Drug: Co-amoxiclav; Augmentin 1.2g IV three times daily for 24 hours. If the patient is randomised to the 5-day duration antibiotic arm then Augmentin 625mg oral tablets three times daily are added to the 24 hour course for a further 4 days.; Other Names: Augmentin; Drug: Iodine; Intra-operative skin preparation prior to incision to skin.; Other Names: Povidone iodine (alcoholic solution); Drug: Metronidazole; 500mg IV three times daily for 24 hours. If the patient is randomised to 5-day duration arm, then another 4 days of oral metronidazole at 400mg three times daily is added to the course; Other Names: Flagyl; Drug: Chlorhexidine; Alcoholic Chlorhexidine skin pre-op preparation; Other Names: Hydrex; Drug: Teicoplanin; Teicoplanin 400mg on induction. If penicillin allergic and on 5-day antibiotic arm then add clindamycin 300mg 4 times daily for further 4 days
Active Comparator: 5 day antibiotic Course; 24 hours of IV antibiotics followed by 4 days of oral antibiotics (Augmentin and metronidazole. Teicoplanin and or gentamicin will be used if penicillin allergic and state of renal function. Clindamycin will be used as a an oral replacement for penicillin allergic patients)	Drug: Co-amoxiclav; Augmentin 1.2g IV three times daily for 24 hours. If the patient is randomised to the 5-day duration antibiotic arm then Augmentin 625mg oral tablets three times daily are added to the 24 hour course for a further 4 days.; Other Names: Augmentin; Drug: Iodine; Intra-operative skin preparation prior to incision to skin.; Other Names: Povidone iodine (alcoholic solution); Drug: Metronidazole; 500mg IV three times daily for 24 hours. If the patient is randomised to 5-day duration arm, then another 4 days of oral metronidazole at 400mg three times daily is added to the course; Other Names: Flagyl; Drug: Chlorhexidine; Alcoholic Chlorhexidine skin pre-op preparation; Other Names: Hydrex; Drug: Teicoplanin; Teicoplanin 400mg on induction. If penicillin allergic and on 5-day antibiotic arm then add clindamycin 300mg 4 times daily for further 4 days; Drug: Clindamycin; Clindamycin 300mg 4 times daily orally to be used in case of penicillin allergy
Active Comparator: Iodine; Skin Preparation used pre-operatively: Alcoholic Povidone	Drug: Co-amoxiclav; Augmentin 1.2g IV three times daily for 24 hours. If the patient is randomised to the 5-day duration antibiotic arm then Augmentin 625mg oral tablets three times daily are added to the 24 hour course for a further 4 days.; Other Names: Augmentin; Drug: Iodine; Intra-operative skin preparation prior to incision to skin.; Other Names: Povidone iodine (alcoholic solution); Drug: Metronidazole; 500mg IV three times daily for 24 hours. If the patient is randomised to 5-day duration arm, then another 4 days of oral metronidazole at 400mg three times daily is added to the course; Other Names: Flagyl; Drug: Teicoplanin; Teicoplanin 400mg on induction. If penicillin allergic and on 5-day antibiotic arm then add clindamycin 300mg 4 times daily for further 4 days; Drug: Clindamycin; Clindamycin 300mg 4 times daily orally to be used in case of penicillin allergy
Active Comparator: Chlorhexidine; Skin preparation to be used preoperatively: Alcoholic chlorhexidine	Drug: Co-amoxiclav; Augmentin 1.2g IV three times daily for 24 hours. If the patient is randomised to the 5-day duration antibiotic arm then Augmentin 625mg oral tablets three times daily are added to the 24 hour course for a further 4 days.; Other Names: Augmentin; Drug: Metronidazole; 500mg IV three times daily for 24 hours. If the patient is randomised to 5-day duration arm, then another 4 days of oral metronidazole at 400mg three times daily is added to the course; Other Names: Flagyl; Drug: Chlorhexidine; Alcoholic Chlorhexidine skin pre-op preparation; Other Names: Hydrex; Drug: Teicoplanin; Teicoplanin 400mg on induction. If penicillin allergic and on 5-day antibiotic arm then add clindamycin 300mg 4 times daily for further 4 days; Drug: Clindamycin; Clindamycin 300mg 4 times daily orally to be used in case of penicillin allergy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical Site Infection	Primary objective: to establish the effect of 5 days of antibiotics versus a 24-hour prophylactic course on the incidence of surgical site infection (SSI) - total ASEPSIS score >21	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of different skin preparations on infection rates	ASEPSIS Questionnaire score >21	30 days
Rate of re-intervention	Types of re-intervention: angioplasty, bypass, debridement, revision to higher level amputation.	30 days
Mortality	Mortality of a patient	1 year
Satisfactory healing rates	Metric Measurement. Asepsis score derived by HPA post-discharge questionnaire. Clinical examination, quality of life, time to prosthesis also recorded.	3 months
Quality of life Questionnaire	Assessed with Short form (SF)-12 questionnaire	1 year
Resource use	length of stay, return to surgery, number of visits to general practitioners, hospital visits, and prescription of antibiotics.	up to 3 months
Rate of C. Diff., MSSA (Methicillin Sensitive Staphylococcus Aureus), MRSA (Methicillin Resistant Staphylococcus Aureus) infection	Infection progress	30 days
Mobility	Locomotor Capabilities index - 5	1 year
Pain Control	McGill Pain questionnaire	1 year

Collaborators and Investigators

• Sponsor: Hull University Teaching Hospitals NHS Trust
• Collaborators: University of Hull

Publications and helpful links

General Publications

• Souroullas P, Barnes R, Carradice D, Smith G, Huang C, Chetter I. Extended-course antibiotic prophylaxis in lower limb amputation: randomized clinical trial. Br J Surg. 2022 Apr 19;109(5):426-432. doi: 10.1093/bjs/znac053.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2013
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): January 2, 2017

Study Registration Dates

• First Submitted: December 5, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (Estimate): December 23, 2013

Study Record Updates

• Last Update Posted (Actual): July 15, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Infection; Amputation; Wound; SSI; Stump; Skin Preparation
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Disease Attributes; Infections; Communicable Diseases; Wounds and Injuries; Surgical Wound Infection; Wound Infection; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Enzyme Inhibitors; Trace Elements; Micronutrients; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; beta-Lactamase Inhibitors; Disinfectants; Plasma Substitutes; Blood Substitutes; Metronidazole; Iodine; Clindamycin; Chlorhexidine; Povidone-Iodine; Povidone; Amoxicillin-Potassium Clavulanate Combination; Teicoplanin
• Other Study ID Numbers: ASSIT Trial