Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S.Aureus in Patients at Risk of Post-op Staphylococcal Infection
Condition: Staphylococcal Infections; Surgical Site Infection
MeSH terms: Infections; Communicable Diseases; Surgical Wound Infection; Staphylococcal Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      This study looks at the difference between XF-73 and placebo in reducing the carriage of a
      bacteria S. aureus in the nose before, during and after heart surgery. Only people who
      normally have S.aureus in their nose will be enrolled onto the study. This will be confirmed
      by analysis of a nasal swab (a cotton bud placed in the nose) before entering the study. It
      is expected 125 people will participate in this study. Participation will be confirmed by
      analysis of a nasal swab (a cotton bud placed in the nose) before entering the study. XF-73
      or placebo will be given 5 times, with an equal chance of participants receiving either XF-73
      or placebo. During the hospital stay more nasal swabs will be taken to determine the amount
      of S.aureus present in the participant's nose. Other tests such as blood samples, blood
      pressure and an examination of the nose and sense of smell will be performed as part of the
      safety assessment. After the hospital stay participants will be followed up for 30 days or if
      a device has been inserted into the body as part of the surgery for 90 days to look at the
      rates of post-operative infection between the placebo and XF-73 groups. The study will run
      for about 18 months. During this period, an independent data monitoring committee will review
      the study to make sure that the balance of benefits and risks of participating in the study
      does not change.
    

Detailed description: 
      This is a multi-centre, double blind, randomized, placebo-controlled study of multiple
      applications of a single concentration of XF-73 nasal gel to assess the microbiological
      effect of XF-73 on commensal S. aureus nasal carriage in patients scheduled for surgical
      procedures deemed to be at high risk of post-operative S. aureus infection. The study is
      divided in 4 periods: screening (days -14 to -1) randomization (days -10 to -1), treatment
      (days -1 and 0) and follow-up (post-last study dose to day 30 or day 90 if an implant is
      inserted during surgery). Day 0 is the calendar day in which surgery takes place. Only
      patients who test positive to S. aureus by a centrally-performed rapid diagnostic test will
      be enrolled in the study. Approximately 125 patients will be randomly allocated in a 1:1
      ratio to 0.2% w/w XF-73 nasal gel treatment OR placebo to match XF-73 nasal gel.

      The study drug, 0.2% w/w XF-73, or matched placebo will be administered 4 times into each
      nostril over 24 hours prior to surgery and then a single application immediately upon closure
      of surgical wound. Additionally, patients may undergo chlorhexidine skin decolonisation ahead
      of surgery and receive perioperative prophylactic systemic antibiotics in accordance with
      local practice.

      Efficacy will be assessed by S. aureus colonisation from screening to 7 days after surgery as
      well as by incidence of post-operative staphylococcal infections and use of
      anti-staphylococcal antibiotics post-surgery. Safety will be assessed by reported adverse
      events (AEs) from screening up to Day 7 as well as vital signs, physical examination (ENT),
      clinical laboratory assessments (haematology, clinical chemistry, and urinalysis) and Smell
      Identification Tests at different time points throughout the study.

      The maximum study duration will be 45 or 105 days for each individual (from screening to
      post-study follow-up visit) depending on whether a foreign implant was inserted during
      surgery.

      An independent data monitoring committee (IDMC) will be set up which will review the safety
      information from the study, the incidence of post-operative staphylococcal infections and to
      ensure that the balance of benefits and risks of participating in the study does not change.
    

Intervention name(s): XF-73; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): XF-73 is a dicationic porphyrin derivative having potent bactericidal properties with a novel mode of action.; Placebo to match XF-73 nasal gel for colour and viscosity.
Other intervention name(s): Exeporfinium chloride; Matched Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Post-operative; Post-surgical; Infection prevention; Staphylococcus aureus; MSSA; MRSA