Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 16 of 24 for:    Porphyrins

Effect of Exeporfinium Chloride (XF-73) Gel on Nasal S. Aureus in Patients at Risk of Post-op Staphylococcal Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03915470
Recruitment Status : Recruiting
First Posted : April 16, 2019
Last Update Posted : August 22, 2019
Sponsor:
Information provided by (Responsible Party):
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 200 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 9 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.

Condition or disease Intervention/treatment Phase
Staphylococcal Infections Surgical Site Infection Drug: XF-73 Drug: Placebo Phase 2

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 -3) randomization (days -10 to -2), 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 200 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double blind.
Primary Purpose: Prevention
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
Actual Study Start Date : June 11, 2019
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: XF-73
XF-73 is a dicationic porphyrin derivative having potent bactericidal properties with a novel mode of action.
Other Name: Exeporfinium chloride

Placebo Comparator: Placebo
0.3 mL applications in each naris of placebo to match XF-73 nasal gel.
Drug: Placebo
Placebo to match XF-73 nasal gel for colour and viscosity.
Other Name: Matched Placebo




Primary Outcome Measures :
  1. Change in S. aureus log CFU/mL from baseline to pre-surgery [ Time Frame: Baseline to immediately prior to 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 :
  1. Difference in AUC of S. aureus log CFU/mL from baseline to pre-surgery [ Time Frame: Baseline to immediately prior to surgery ]
    To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden from baseline to pre-surgery and from baseline to immediately post-surgery measured as area under the curve (AUC) of S. aureus log CFUs/mL over time.

  2. Difference in AUC of S. aureus log CFU/mL from baseline to immediately post-surgery [ Time Frame: Baseline to immediately post surgery ]
    To determine the effect of a 0.2% XF-73 nasal gel on S. aureus nasal burden from baseline to pre-surgery and from baseline to immediately post-surgery measured as area under the curve (AUC) of S. aureus log CFUs/mL over time.

  3. Change in S. aureus log CFU/mL from immediately after surgery to 48 hours after surgery [ Time Frame: From immediately after surgery 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 after last administration.

  4. Change in S. aureus log CFU/mL from immediately after surgery to 6 days (± 24hrs) after surgery [ Time Frame: From immediately after surgery to follow-up Day 6 ± 24hrs 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 after last administration.

  5. Percentage of patients reaching a specific reduction in S. aureus carriage prior to surgery, immediately post-surgery and on Day 6 ± 24hrs. [ Time Frame: Immediately prior to surgery, immediately post-surgery and on Day 6 ± 24hrs. ]
    To explore the efficacy of XF-73 in reducing the burden of S. aureus carriage at the patient level.

  6. Difference in the incidence of staphylococcal post-operative infections during the 30-day period after surgery (90 days in the case of foreign implant) [ Time Frame: 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).

  7. Incidence of treatment-emergent adverse events from the first dose of study medication to 6 days (± 24hrs) after last dose of study medication. [ Time Frame: Immediately prior to surgery until Day 6 ± 24hrs. ]
    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.

  8. Change in mean blood pressure (mmHg) [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    Mean systolic and diastolic blood pressure (mmHg) changes from baseline, at post study treatment 48h ± 24h and Day 6± 24h.

  9. Change in mean heart rate (bpm) [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    Mean heart rate (bpm) changes from baseline, at post study treatment 48h ± 24h and Day 6± 24h.

  10. Changes in nasal examination. [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    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 prior to first dose at 48h ± 24h and Day 6± 24h.

  11. Changes in brief smell identification test (B-SIT). [ Time Frame: From Randomisation until Day 6 ± 24hrs. ]
    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 B-SIT score, assessment and percentile ranking changes from prior to first dose at Day 6± 24h.


Other Outcome Measures:
  1. Number prescriptions of anti-staphylococcal antibiotics. [ Time Frame: From immediately post-surgery to 30 days post surgery (90 days in the case of foreign implant) ]
    To describe the frequency in prescription of post-operative anti-staphylococcal antibiotics in terms of number prescriptions, except those provided for prophylaxis as local standard of care (SOC), during the 30 day post-surgery period (90 days in the case of an object implant) reported separately.

  2. Number of patients requiring anti-staphylococcal antibiotics. [ Time Frame: From immediately post-surgery to 30 days post surgery (90 days in the case of foreign implant) ]
    To describe the frequency in terms of the number of patients requiring anti-staphylococcal antibiotics, except those provided for prophylaxis as local standard of care (SOC), during the 30 day post-surgery period (90 days in the case of an object implant) reported separately.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Clinically significant abnormalities in vital signs or laboratory analyses at 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03915470


Contacts
Layout table for location contacts
Contact: Director of Clinical Projects +44 (0)1273 704440 participation@destinypharma.com

Locations
Layout table for location information
United States, Idaho
Snake River Research, PLLC Recruiting
Pocatello, Idaho, United States, 83201
Contact: Study Coordinator         
Principal Investigator: Jacob DeLaRosa, MD         
United States, Texas
Memorial Hermann - Memorial City Medical Center Recruiting
Houston, Texas, United States, 77024
Contact: Study Coordinator         
Principal Investigator: Wiener, MD         
Georgia
Ltd Israel-Georgia Medical Research Clinic Helsicore Recruiting
Tbilisi, Georgia, 0112
Contact: Study Coordinator         
Principal Investigator: Nodar Emukhvari, MD, PhD         
Ltd "Open Heart" Recruiting
Tbilisi, Georgia, 0141
Contact: Study Coordinator         
Principal Investigator: Kakhaber Latsuzbaia, MD         
Ltd Acad. G.Chapidze Emergency Cardiology Center Recruiting
Tbilisi, Georgia, 0159
Contact: Study Coordinator         
Principal Investigator: Vakhtang Chumburidze, MD, PhD         
Ltd Bokhua Memorial Cardiovascular Center Recruiting
Tbilisi, Georgia, 0159
Contact: Study Coordinator         
Principal Investigator: Zaza Katsitadze, MD, PhD         
Ltd Tbilisi Heart and Vascular Clinic Recruiting
Tbilisi, Georgia, 0159
Contact: Study Coordinator         
Principal Investigator: Tamaz Shaburishvili, MD, PhD         
Ltd Tbilisi Heart Center Recruiting
Tbilisi, Georgia, 0186
Contact: Study Coordinator         
Principal Investigator: Irakli Beridze, MD, PhD         
Sponsors and Collaborators
Destiny Pharma Plc
Investigators
Layout table for investigator information
Study Chair: Jesus M Gonzalez Moreno, MD Destiny Pharma Plc
Study Director: Jim P Lees, BSc Destiny Pharma Plc

Layout table for additonal information
Responsible Party: Destiny Pharma Plc
ClinicalTrials.gov Identifier: NCT03915470     History of Changes
Other Study ID Numbers: XF-73B07
First Posted: April 16, 2019    Key Record Dates
Last Update Posted: August 22, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Destiny Pharma Plc:
Post-operative
Post-surgical
Infection prevention
Staphylococcus aureus
MSSA
MRSA
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Surgical Wound Infection
Staphylococcal Infections
Wound Infection
Postoperative Complications
Pathologic Processes
Gram-Positive Bacterial Infections
Bacterial Infections