The Amputation Surgical Site Infection Trial (ASSIT)

NCT02018094 | Completed Phase 4 DMC

• 1 other identifier: ASSIT Trial
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

• 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.

Conditions

Wound Infection; Amputation Wound

Keywords

Amputation; Infection; Skin Preparation; SSI; Stump; Wound

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Impact of different skin preparations on infection rates

  30 days

• Rate of re-intervention

  30 days

• Mortality

  1 year

• Satisfactory healing rates

  3 months

• Quality of life Questionnaire

  1 year

Study Arms (4)

24 hour antibiotic course

ACTIVE COMPARATOR

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; Drug: Iodine; Drug: Metronidazole; Drug: Chlorhexidine; Drug: Teicoplanin

5 day antibiotic Course

ACTIVE COMPARATOR

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; Drug: Iodine; Drug: Metronidazole; Drug: Chlorhexidine; Drug: Teicoplanin; Drug: Clindamycin

Iodine

ACTIVE COMPARATOR

Skin Preparation used pre-operatively: Alcoholic Povidone

Drug: Co-amoxiclav; Drug: Iodine; Drug: Metronidazole; Drug: Teicoplanin; Drug: Clindamycin

Chlorhexidine

ACTIVE COMPARATOR

Skin preparation to be used preoperatively: Alcoholic chlorhexidine

Drug: Co-amoxiclav; Drug: Metronidazole; Drug: Chlorhexidine; Drug: Teicoplanin; Drug: Clindamycin

Interventions

Co-amoxiclav DRUG

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.

Also known as: Augmentin

24 hour antibiotic course; 5 day antibiotic Course; Chlorhexidine; Iodine

Iodine DRUG

Intra-operative skin preparation prior to incision to skin.

Also known as: Povidone iodine (alcoholic solution)

24 hour antibiotic course; 5 day antibiotic Course; Iodine

Metronidazole DRUG

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

Also known as: Flagyl

24 hour antibiotic course; 5 day antibiotic Course; Chlorhexidine; Iodine

Chlorhexidine DRUG

Alcoholic Chlorhexidine skin pre-op preparation

Also known as: Hydrex

24 hour antibiotic course; 5 day antibiotic Course; Chlorhexidine

Teicoplanin DRUG

Teicoplanin 400mg on induction. If penicillin allergic and on 5-day antibiotic arm then add clindamycin 300mg 4 times daily for further 4 days

24 hour antibiotic course; 5 day antibiotic Course; Chlorhexidine; Iodine

Clindamycin DRUG

Clindamycin 300mg 4 times daily orally to be used in case of penicillin allergy

5 day antibiotic Course; Chlorhexidine; Iodine

Eligibility Criteria

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

You may qualify if:

• Adults ≥18 yrs undergoing lower limb amputations who are able to consent to the trial.
• 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)

You may not qualify if:

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

Sponsors & Collaborators

• Hull University Teaching Hospitals NHS Trust: lead
• University of Hull: collaborator

Study Sites (1)

Hull Royal Infirmary

Hull, HU3 2JZ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35325055 DERIVED

MeSH Terms

Conditions

Wound Infection; Infections; Wounds and Injuries

Interventions

Amoxicillin-Potassium Clavulanate Combination; Iodine; Povidone-Iodine; Metronidazole; Chlorhexidine; Hydrex; Teicoplanin; Clindamycin

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Halogens; Elements; Inorganic Chemicals; Iodophors; Iodine Compounds; Polyvinyls; Vinyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Povidone; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Biguanides; Guanidines; Amidines; Lipoglycopeptides; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Lincomycin; Lincosamides; Glycosides

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2013
• First Posted: December 23, 2013
• Study Start: October 8, 2013
• Primary Completion: March 1, 2014
• Study Completion: January 2, 2017
• Last Updated: July 15, 2019

Record last verified: 2019-07

Locations

GB (1)