Clinical trial NCT03915470: Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S.Aureus in Patients at Risk of Post-op Staphylococcal Infection
Official title: A Phase 2 Study to Assess the Effect of a Repeated Dose of XF-73 Nasal Gel on the Microbiological Burden of Commensal Staphylococcus Aureus Nasal Carriage in Surgical Patients at Risk of Post-operative Staphylococcal Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Staphylococcal Infections
Surgical Site Infection
Keywords: Post-operative
Post-surgical
Infection prevention
Staphylococcus aureus
MSSA
MRSA
Lead sponsor: Destiny Pharma Plc
Sponsor class: INDUSTRY
First posted: 2019-04-16
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Individuals who meet all of the following criteria are eligible to participate in the study.

1. Male or female patients between 18 and 75 years of age.
2. Patients who are confirmed nasal S. aureus carriers by polymerase chain reaction (PCR) screen assay, and due to undergo surgical procedure.
3. Patients who are willing to provide written informed consent.
4. Patients who are willing and able (as per Investigator judgment) to complete all protocol specified visits and assessments.
5. Woman of childbearing potential\* with a negative urine pregnancy test (sensitive to 25 IU human chorionic gonadotropin (hCG)).

   * Women of childbearing potential are defined as those women between menarche and menopause who have not undergone permanent sterilisation. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.

Individuals who meet any of the following criteria are not eligible to participate in the study.

1. Pregnancy (current) or currently lactating.
2. Uncontrolled acute or chronic illness (as determined by the investigator) in addition to those requiring the planned surgical intervention.
3. History of atopy, allergic reactions or hypersensitivity to the study medication or its components.
4. Current upper respiratory tract infection, cold or influenza with significant nasal symptoms that might impact on the patient's ability to comply with the gel application procedure.
5. History of photosensitivity.
6. Family history of porphyria.
7. Use of intra-nasal topical or systemic antibiotics or anti-infectives within the last 4 weeks before screening. (Patients who screen positive for nasal carriage of S. aureus and receive topical or systemic antibiotics or anti-infectives which are not part of their prophylactic peri-operative SOC between screening and first dose of investigational medicinal product (IMP) will be excluded from the study.) The use of intra-nasal antibiotics or anti-infectives other than the study medication prior to surgery is not allowed.
8. Use of other prescribed or over the counter nasal medication in the last 14 days, or oral decongestants in the last 7 days before first administration of study drug.
9. Participation in a clinical trial within the last 12 weeks before first administration of study drug.
10. Contemporaneous clinically significant abnormalities in vital signs or laboratory analyses reported within 14 days prior to randomization which in the opinion of the Investigator would preclude from the safety assessment of the medication under study.
11. Nasal polyps or significant anatomical or other nasal abnormality that would prevent from appropriate administration of the study treatment or represent an excessive risk for the patient's participation.
12. History of nasal surgery including cauterization.
13. A recent history of frequent epistaxis and/or an episode of epistaxis within 3 months of the planned surgery.
14. Use of in situ nasal jewellery or existence of open nasal piercings.

Primary outcomes:
measure: Change in S. Aureus Log CFU/mL From Baseline to Pre-surgery
timeFrame: Baseline (Day-10 to Day-1) to immediately prior to surgery (Day 0)
Secondary outcomes:
measure: Change in S. Aureus Log CFU/mL From Baseline to Immediately Post-surgery
timeFrame: From baseline (day -10 to Day -1) to immediately post surgery (Day 0)
measure: Change in S. Aureus Log CFU/mL From Baseline to 48 Hours After Surgery
timeFrame: From baseline to follow-up at 48 hours after surgery
measure: Change in S. Aureus Log CFU/mL From Baseline to Immediately After Surgery to 6 Days (± 24hours) After Surgery
timeFrame: From baseline to follow-up Day 6 ± 24hours after surgery
measure: Number of Participants With Staphylococcal Post-operative Infections During the 30-day Period After Surgery (90 Days in the Case of Foreign Implant)
timeFrame: From immediately post-surgery to 30 days post surgery (90 days in the case of foreign implant)
measure: Incidence of Treatment-emergent Adverse Events From the First Dose of Study Medication to 6 Days (± 24hours) After Last Dose of Study Medication.
timeFrame: Immediately prior to surgery until Day 6 ± 24hours.
measure: Changes in Nasal Examination.
timeFrame: From Randomisation (Day -10 to Day -1) until 48hours ± 24hours post surgery.
measure: Changes in Brief Smell Identification Test (B-SIT).
timeFrame: From Randomisation (Day -10 to Day -1) until Day 6 ± 24hours post surgery
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Pocatello
country: United States
facility: Snake River Research, PLLC
state: Idaho
city: Des Moines
country: United States
facility: MercyOne Iowa Heart Center
state: Iowa
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Columbia
country: United States
facility: University of Missouri Health Care
state: Missouri
city: Houston
country: United States
facility: Memorial Hermann - Memorial City Medical Center
state: Texas
city: Tacoma
country: United States
facility: CHI Franciscan Research Center
state: Washington
city: Kutaisi
country: Georgia
facility: Ltd Clinic LJ
city: Tbilisi
country: Georgia
facility: Ltd Israel-Georgia Medical Research Clinic Helsicore
city: Tbilisi
country: Georgia
facility: Ltd "Open Heart"
city: Tbilisi
country: Georgia
facility: Ltd Cardiology Clinic Guli
city: Tbilisi
country: Georgia
facility: Ltd Acad. G.Chapidze Emergency Cardiology Center
city: Tbilisi
country: Georgia
facility: Ltd Bokhua Memorial Cardiovascular Center
city: Tbilisi
country: Georgia
facility: Ltd Tbilisi Heart and Vascular Clinic
city: Tbilisi
country: Georgia
facility: Ltd Clinic Jerarsi
city: Tbilisi
country: Georgia
facility: Ltd Tbilisi Heart Center
city: Tbilisi
country: Georgia
facility: JSC Evex Hospitals
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Clinic for Cardiac Surgery, Institute for Cardiovascular Disease-Deinje
city: Niš
country: Serbia
facility: Clinical Center Nis
city: Sremska Kamenica
country: Serbia
facility: Institute for Cardiovascular Disease of Vojvodina
Study officials:
affiliation: Destiny Pharma Plc
name: Jesus M Gonzalez Moreno, MD
role: STUDY_CHAIR
affiliation: Destiny Pharma Plc
name: Jim P Lees, BSc
role: STUDY_DIRECTOR
References:
citation: Mangino JE, Firstenberg MS, Milewski RKC, Rhys-Williams W, Lees JP, Dane A, Love WG, Gonzalez Moreno J. Exeporfinium chloride (XF-73) nasal gel dosed over 24 hours prior to surgery significantly reduced Staphylococcus aureus nasal carriage in cardiac surgery patients: Safety and efficacy results from a randomized placebo-controlled phase 2 study. Infect Control Hosp Epidemiol. 2023 Jul;44(7):1171-1173. doi: 10.1017/ice.2023.17. Epub 2023 Mar 23.