Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S.Aureus in Patients at Risk of Post-op Staphylococcal Infection
- Conditions
- Staphylococcal InfectionsSurgical Site Infection
- Interventions
- Drug: Placebo
- Registration Number
- NCT03915470
- Lead Sponsor
- Destiny Pharma Plc
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 124
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 0.3 mL applications in each naris of placebo to match XF-73 nasal gel. XF-73 XF-73 0.3 mL applications in each naris of 0.2% w/w XF-73 nasal gel for a cumulative dose of 6.0 mg of XF-73.
- Primary Outcome Measures
Name Time Method Change in S. Aureus Log CFU/mL From Baseline to Pre-surgery Baseline (Day-10 to Day-1) to immediately prior to surgery (Day 0) To demonstrate the efficacy of a 0.2% XF-73 nasal gel in reducing the microbiological burden of nasal S. aureus measured as change in colony forming units (CFU) per millilitre (mL) from baseline to immediately prior to surgery in a patient population at risk of post-operative staphylococcal infection
- Secondary Outcome Measures
Name Time Method Change in S. Aureus Log CFU/mL From Baseline to Immediately After Surgery to 6 Days (± 24hours) After Surgery From baseline to follow-up Day 6 ± 24hours after surgery To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden measured as CFUs/mL in follow-up 7 days after last administration.
Incidence of Treatment-emergent Adverse Events From the First Dose of Study Medication to 6 Days (± 24hours) After Last Dose of Study Medication. Immediately prior to surgery until Day 6 ± 24hours. To describe the safety and tolerability of multiple administrations of a 0.2% XF-73 nasal gel in a population of surgical patients at risk of post-operative staphylococcal infections.
Change in S. Aureus Log CFU/mL From Baseline to Immediately Post-surgery From baseline (day -10 to Day -1) to immediately post surgery (Day 0) To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden measured as CFUs/mL in follow-up after last administration.
Changes in Nasal Examination. From Randomisation (Day -10 to Day -1) until 48hours ± 24hours post surgery. To describe the safety and tolerability of multiple administrations of a 0.2% XF-73 nasal gel in a population of surgical patients at risk of post-operative staphylococcal infections by comparison of changes in ENT specialist nasal examination findings from randomisation to 48hours ± 24hours post surgery.
Change in S. Aureus Log CFU/mL From Baseline to 48 Hours After Surgery From baseline to follow-up at 48 hours after surgery To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden measured as CFUs/mL in follow-up 48 hours after last administration.
Changes in Brief Smell Identification Test (B-SIT). From Randomisation (Day -10 to Day -1) until Day 6 ± 24hours post surgery To describe the safety and tolerability of multiple administrations of a 0.2% XF-73 nasal gel in a population of surgical patients at risk of post-operative staphylococcal infections by comparison of Brief Smell Identification Test (B-SIT) score, assessment and percentile ranking changes from prior to first dose until Day 6 ±24h post surgery.
Patients are asked to identify 12 unique smells; the more smells they identify correctly the higher the score (0-12). Comparison of the individual patient score is then made against their expected percentile ranking dependent on age and sex of the general population to determine if their percentile ranking is normal, abnormal relative to age or deficit relative to younger persons.Number of Participants With Staphylococcal Post-operative Infections During the 30-day Period After Surgery (90 Days in the Case of Foreign Implant) From immediately post-surgery to 30 days post surgery (90 days in the case of foreign implant) To assess the effect of XF-73 on S. aureus nasal carriage in the prevention of post-operative staphylococcal infections (surgical site infection, blood stream infections, and others) during the 30 days post-surgery (90 days in the case of a foreign implant).
Trial Locations
- Locations (21)
CHI Franciscan Research Center
🇺🇸Tacoma, Washington, United States
Clinical Center Nis
🇷🇸Niš, Serbia
University of Missouri Health Care
🇺🇸Columbia, Missouri, United States
Memorial Hermann - Memorial City Medical Center
🇺🇸Houston, Texas, United States
MercyOne Iowa Heart Center
🇺🇸Des Moines, Iowa, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
JSC Evex Hospitals
🇬🇪Tbilisi, Georgia
Ltd Tbilisi Heart and Vascular Clinic
🇬🇪Tbilisi, Georgia
Institute for Cardiovascular Disease of Vojvodina
🇷🇸Sremska Kamenica, Serbia
Snake River Research, PLLC
🇺🇸Pocatello, Idaho, United States
Ltd Cardiology Clinic Guli
🇬🇪Tbilisi, Georgia
Ltd Clinic LJ
🇬🇪Kutaisi, Georgia
Ltd Acad. G.Chapidze Emergency Cardiology Center
🇬🇪Tbilisi, Georgia
Ltd Israel-Georgia Medical Research Clinic Helsicore
🇬🇪Tbilisi, Georgia
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Ltd "Open Heart"
🇬🇪Tbilisi, Georgia
Ltd Bokhua Memorial Cardiovascular Center
🇬🇪Tbilisi, Georgia
Ltd Clinic Jerarsi
🇬🇪Tbilisi, Georgia
Ltd Tbilisi Heart Center
🇬🇪Tbilisi, Georgia
Clinic for Cardiac Surgery, Institute for Cardiovascular Disease-Deinje
🇷🇸Belgrade, Serbia
University of Florida
🇺🇸Gainesville, Florida, United States