Back to resultsEffect of Exeporfinium Chloride (XF-73) Gel on Nasal S.Aureus in Patients at Risk of Post-op Staphylococcal Infection
Primary Purpose
Staphylococcal Infections, Surgical Site Infection
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
XF-73
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Staphylococcal Infections focused on measuring Post-operative, Post-surgical, Infection prevention, Staphylococcus aureus, MSSA, MRSA
Eligibility Criteria
Individuals who meet all of the following criteria are eligible to participate in the study.
- Male or female patients between 18 and 75 years of age.
- Patients who are confirmed nasal S. aureus carriers by polymerase chain reaction (PCR) screen assay, and due to undergo surgical procedure.
- Patients who are willing to provide written informed consent.
- Patients who are willing and able (as per Investigator judgment) to complete all protocol specified visits and assessments.
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.
- Pregnancy (current) or currently lactating.
- Uncontrolled acute or chronic illness (as determined by the investigator) in addition to those requiring the planned surgical intervention.
- History of atopy, allergic reactions or hypersensitivity to the study medication or its components.
- 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.
- History of photosensitivity.
- Family history of porphyria.
- 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.
- 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.
- Participation in a clinical trial within the last 12 weeks before first administration of study drug.
- 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.
- 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.
- History of nasal surgery including cauterization.
- A recent history of frequent epistaxis and/or an episode of epistaxis within 3 months of the planned surgery.
- Use of in situ nasal jewellery or existence of open nasal piercings.
Sites / Locations
- University of Florida
- Snake River Research, PLLC
- MercyOne Iowa Heart Center
- Ochsner Clinic Foundation
- University of Missouri Health Care
- Memorial Hermann - Memorial City Medical Center
- CHI Franciscan Research Center
- Ltd Clinic LJ
- Ltd Israel-Georgia Medical Research Clinic Helsicore
- Ltd "Open Heart"
- Ltd Cardiology Clinic Guli
- Ltd Acad. G.Chapidze Emergency Cardiology Center
- Ltd Bokhua Memorial Cardiovascular Center
- Ltd Tbilisi Heart and Vascular Clinic
- Ltd Clinic Jerarsi
- Ltd Tbilisi Heart Center
- JSC Evex Hospitals
- Clinical Center of Serbia
- Clinic for Cardiac Surgery, Institute for Cardiovascular Disease-Deinje
- Clinical Center Nis
- Institute for Cardiovascular Disease of Vojvodina
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
XF-73
Placebo
Arm Description
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.
0.3 mL applications in each naris of placebo to match XF-73 nasal gel.
Outcomes
Primary Outcome Measures
Change in S. Aureus Log CFU/mL From Baseline to Pre-surgery
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
Change in S. Aureus Log CFU/mL From Baseline to Immediately Post-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 after last administration.
Change in S. Aureus Log CFU/mL From Baseline to 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.
Change in S. Aureus Log CFU/mL From Baseline to Immediately After Surgery to 6 Days (± 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.
Number of Participants With Staphylococcal Post-operative Infections During the 30-day Period After 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).
Incidence of Treatment-emergent Adverse Events From the First Dose of Study Medication to 6 Days (± 24hours) After Last Dose of Study Medication.
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.
Changes in Nasal Examination.
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.
Changes in Brief Smell Identification Test (B-SIT).
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03915470
Brief Title
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
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
August 29, 2019 (Actual)
Primary Completion Date
January 4, 2021 (Actual)
Study Completion Date
March 29, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Destiny Pharma Plc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Staphylococcal Infections, Surgical Site Infection
Keywords
Post-operative, Post-surgical, Infection prevention, Staphylococcus aureus, MSSA, MRSA
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Double blind.
Allocation
Randomized
Enrollment
124 (Actual)
8. Arms, Groups, and Interventions
Arm Title
XF-73
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
0.3 mL applications in each naris of placebo to match XF-73 nasal gel.
Intervention Type
Drug
Intervention Name(s)
XF-73
Other Intervention Name(s)
Exeporfinium chloride
Intervention Description
XF-73 is a dicationic porphyrin derivative having potent bactericidal properties with a novel mode of action.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Matched Placebo
Intervention Description
Placebo to match XF-73 nasal gel for colour and viscosity.
Primary Outcome Measure Information:
Title
Change in S. Aureus Log CFU/mL From Baseline to Pre-surgery
Description
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
Time Frame
Baseline (Day-10 to Day-1) to immediately prior to surgery (Day 0)
Secondary Outcome Measure Information:
Title
Change in S. Aureus Log CFU/mL From Baseline to Immediately Post-surgery
Description
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.
Time Frame
From baseline (day -10 to Day -1) to immediately post surgery (Day 0)
Title
Change in S. Aureus Log CFU/mL From Baseline to 48 Hours After Surgery
Description
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.
Time Frame
From baseline to follow-up at 48 hours after surgery
Title
Change in S. Aureus Log CFU/mL From Baseline to Immediately After Surgery to 6 Days (± 24hours) After Surgery
Description
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.
Time Frame
From baseline to follow-up Day 6 ± 24hours after surgery
Title
Number of Participants With Staphylococcal Post-operative Infections During the 30-day Period After Surgery (90 Days in the Case of Foreign Implant)
Description
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).
Time Frame
From immediately post-surgery to 30 days post surgery (90 days in the case of foreign implant)
Title
Incidence of Treatment-emergent Adverse Events From the First Dose of Study Medication to 6 Days (± 24hours) After Last Dose of Study Medication.
Description
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.
Time Frame
Immediately prior to surgery until Day 6 ± 24hours.
Title
Changes in Nasal Examination.
Description
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.
Time Frame
From Randomisation (Day -10 to Day -1) until 48hours ± 24hours post surgery.
Title
Changes in Brief Smell Identification Test (B-SIT).
Description
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.
Time Frame
From Randomisation (Day -10 to Day -1) until Day 6 ± 24hours post surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Individuals who meet all of the following criteria are eligible to participate in the study.
Male or female patients between 18 and 75 years of age.
Patients who are confirmed nasal S. aureus carriers by polymerase chain reaction (PCR) screen assay, and due to undergo surgical procedure.
Patients who are willing to provide written informed consent.
Patients who are willing and able (as per Investigator judgment) to complete all protocol specified visits and assessments.
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.
Pregnancy (current) or currently lactating.
Uncontrolled acute or chronic illness (as determined by the investigator) in addition to those requiring the planned surgical intervention.
History of atopy, allergic reactions or hypersensitivity to the study medication or its components.
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.
History of photosensitivity.
Family history of porphyria.
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.
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.
Participation in a clinical trial within the last 12 weeks before first administration of study drug.
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.
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.
History of nasal surgery including cauterization.
A recent history of frequent epistaxis and/or an episode of epistaxis within 3 months of the planned surgery.
Use of in situ nasal jewellery or existence of open nasal piercings.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jesus M Gonzalez Moreno, MD
Organizational Affiliation
Destiny Pharma Plc
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jim P Lees, BSc
Organizational Affiliation
Destiny Pharma Plc
Official's Role
Study Director
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Snake River Research, PLLC
City
Pocatello
State/Province
Idaho
ZIP/Postal Code
83201
Country
United States
Facility Name
MercyOne Iowa Heart Center
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50314
Country
United States
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
University of Missouri Health Care
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
Memorial Hermann - Memorial City Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
CHI Franciscan Research Center
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Ltd Clinic LJ
City
Kutaisi
ZIP/Postal Code
4600
Country
Georgia
Facility Name
Ltd Israel-Georgia Medical Research Clinic Helsicore
City
Tbilisi
ZIP/Postal Code
0112
Country
Georgia
Facility Name
Ltd "Open Heart"
City
Tbilisi
ZIP/Postal Code
0141
Country
Georgia
Facility Name
Ltd Cardiology Clinic Guli
City
Tbilisi
ZIP/Postal Code
0144
Country
Georgia
Facility Name
Ltd Acad. G.Chapidze Emergency Cardiology Center
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Ltd Bokhua Memorial Cardiovascular Center
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Ltd Tbilisi Heart and Vascular Clinic
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Ltd Clinic Jerarsi
City
Tbilisi
ZIP/Postal Code
0167
Country
Georgia
Facility Name
Ltd Tbilisi Heart Center
City
Tbilisi
ZIP/Postal Code
0186
Country
Georgia
Facility Name
JSC Evex Hospitals
City
Tbilisi
ZIP/Postal Code
4600
Country
Georgia
Facility Name
Clinical Center of Serbia
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Clinic for Cardiac Surgery, Institute for Cardiovascular Disease-Deinje
City
Belgrade
ZIP/Postal Code
11040
Country
Serbia
Facility Name
Clinical Center Nis
City
Niš
ZIP/Postal Code
18000
Country
Serbia
Facility Name
Institute for Cardiovascular Disease of Vojvodina
City
Sremska Kamenica
ZIP/Postal Code
21204
Country
Serbia
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
36951472
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 Mar 23;44(7):1-3. doi: 10.1017/ice.2023.17. Online ahead of print.
Results Reference
result
Learn more about this trial
Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S.Aureus in Patients at Risk of Post-op Staphylococcal Infection
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