Oxygen-ozone Therapy Plus Antibiotic Therapy in the Treatment of Infections Secondary to Implant of Orthopaedic Devices

Open-label, Multicentre, Randomized, Parallel Group Study to Assess the Efficacy and Safety of Oxygen-ozone Therapy Plus Oral Antibiotic Therapy in the Treatment of Infections Secondary to Implant of Orthopaedic Devices

This is an open-label, multicentre, randomized, parallel group study to evaluate the efficacy of treatment with oxygen-ozone therapy plus oral antibiotic therapy, in comparison with oral antibiotic therapy alone, in the proportion of patients with resolution/improvement of signs and symptoms of infection of the wound (e.g. ulcer, eschar, sore) in the target lesion after 14 days of treatment, in patients with infections secondary to implant of orthopaedic devices.

Study Overview

• Status: Recruiting
• Conditions: Infection
• Intervention / Treatment: Procedure: Oxygen-ozone therapy

Detailed Description

This will be an open-label, multicentre, randomized, parallel group study. The study plan will include a screening visit (Visit 1, Day -7/-3) in which patients will be screened on the basis of inclusion/exclusion criteria and clinically evaluated.

At the end of the 3-7 days of run-in (Visit 2, Baseline visit, Day 0), patient still eligible will be randomised to one of the two following treatment groups:

1. Oxygen-ozone therapy SIOOT plus antibiotic therapy
2. Antibiotic therapy

Patients in both groups will receive oral antibiotic therapy, which will be prescribed at discretion of the Investigator, based on the results of the colture of the swab collected in the target lesion at the screening visit (and later, if needed) and the associated antibiogram.

Follow-up visits will be performed after 7 days (Visit 3, Day 7), 14 days (Visit 4, Day 14), 28 days (Visit 5, Day 28) and 42 days (Visit 6, End of study, Day 42) from the start of treatment.

A visit window of ± 2 days for the date of Visits 3-5 and of ± 3 days for the date of Visits 6 will be allowed.

Patients prematurely discontinued from the study will perform an 'Early termination visit', in which procedures schedule for Visit 6 (End of study, Day 42) will be performed. In case of premature study discontinuation, the Investigator will duly record the reason for premature withdrawal in the appropriate section of the case report form (eCRF).

Visit 6, or the 'Early termination Visit' will represent the conclusion of patient's participation in the investigation.

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marianno Franzini; Phone Number: 035 19910105; Email: info@ossigenoozono.it

Study Locations

• Italy
  • Ancona, Italy
    • Not yet recruiting
    • Ospedali Riuniti Torrette
    • Contact: Antonio Pompilio Gigante; Email: a.gigante@univpm.it
  • Napoli, Italy
    • Not yet recruiting
    • Università Federico II
    • Contact: Andrea Cozzolino; Email: andrea.cozzolino@hotmail.it
  • Palermo, Italy
    • Not yet recruiting
    • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone di Palermo
    • Contact: Mario Barbagallo; Email: mario.barbagallo@unipa.it
  • Pavia, Italy
    • Not yet recruiting
    • Fondazione IRCCS Policlinico San Matteo
    • Contact: Maria Benedetta Mascia; Email: bennymascia@hotmail.com
  • Roma, Italy
    • Not yet recruiting
    • Casa Di Cura Citta' Di Roma
    • Contact: Riccardo Barchetta; Email: riccardo.barchetta@gmail.com
  • Caserta
    • Castel Volturno, Caserta, Italy
      • Recruiting
      • Pineta Grande Hospital
      • Contact: Antonio Guastafierro; Email: drantonio.guastafierro@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed written informed consent;
2. Male or female aged ≥ 18 years;
3. Patient having undergone surgery for implant of an orthopaedic device in the previous 8 weeks;
4. Presence of at least one (but no more than 3) post-operative wounds in the site of surgery (ulcers, eschars, sores);
5. Presence of at least one symptom (pain, burning, redness and malodour) and at least one sign (erythema, local warmth, swelling, purulent secretion) of infection of at least moderate intensity (score ≥ 2) in the target lesion at the screening visit (Visit 1), to be confirmed again at the baseline visit (Visit 2);
6. Wound area of the target lesion ≤ 100 cm2;
7. Patient with presence at least one pathogen identified in the swab collection in the target lesion, which is amenable to be eradicated with oral antibiotic therapy;
8. In case of multiple wounds (however not more than three), non-target lesions must not overlap with the target one (i.e. the largest one);
9. Patient able to perform the wound self-care at home or care by his/her primary caregiver;
10. Willing to refrain from all non-permitted concomitant medication from the screening visit through to the entire study duration.
11. Female subjects of childbearing potential must have a negative urinary pregnancy test at Screening and must practice a reliable method of contraception throughout the study;
12. Patient able to read and understand the study procedures, the requirements for follow-up visits, willing to provide information at the scheduled evaluations and willing, able and ensuring to comply with the study requirements for the whole study period.

Exclusion Criteria:

1. Wounds without signs of localized infection;
2. Presence of more than four wounds;
3. Presence of one or more wounds with area > 100 cm2;
4. Presence of undermining wounds;
5. Patients with favism, i.e. deficiency of the glucose-6-phosphate dehydrogenase (G6PD) enzyme;
6. Patients with uncontrolled hyperthyroidism;
7. Patients with history of connective tissue disease, e.g., mixed connective tissue disease;
8. Patients with active malignant disease;
9. Patients with other clinically significant diseases, or other major diseases deemed clinically significant by the Investigator or which in the opinion of the Investigator would interfere with the study procedures or study outcome;
10. Patients candidate to any surgery during the overall study duration;
11. Treatment with topical corticosteroids in the previous 4 weeks and/or with systemic corticosteroids in the previous 7 days;
12. Treatment with any hydrating and/or moisturizing cream in the previous 24 hours.
13. Patients on treatment with chemotherapeutic agents, radiation therapy or immunosuppressive therapies;
14. Patients with contraindications to antibiotic therapy;
15. Pregnant, breastfeeding women and female child-bearing potential who are not using a highly effective method of birth control and not willing to use it during the participation to the study;
16. Participation in any clinical research study evaluating another investigational drug or device within 30 days prior to consenting to study entry;
17. Patient unable to understand informed consent or having a high probability of non-compliance with the study procedures and or non-completion of the study according to investigator's judgement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Oxygen-ozone therapy plus antibiotic therapy	Procedure: Oxygen-ozone therapy; Oxygen-ozone therapy (group a) will be performed by: i) Self-haemoinfusion of 200 cc. with concentrations of 40-50 μg/ml, to be performed two/three times a week, for a time of 6 weeks (for a maximum of 15 sessions); ii) Subcutaneous injections in the perilesional site at the dose of 5 cc. with concentrations of 4 μg,/ml, Cleanse wounds with 100 cc of 5-10 ug ozone gas
Other: Arm B; Antibiotic therapy	Procedure: Oxygen-ozone therapy; Oxygen-ozone therapy (group a) will be performed by: i) Self-haemoinfusion of 200 cc. with concentrations of 40-50 μg/ml, to be performed two/three times a week, for a time of 6 weeks (for a maximum of 15 sessions); ii) Subcutaneous injections in the perilesional site at the dose of 5 cc. with concentrations of 4 μg,/ml, Cleanse wounds with 100 cc of 5-10 ug ozone gas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical success at Day 14	Resolution/improvement of signs and symptoms of infection of the wound in the target lesion (i.e. a score ≤ 1 for a maximum of two signs/symptoms) from baseline to Day 14. The following symptoms will be evaluated by patients on a 0-4 point Likert scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom; 4 = very severe symptom): pain, burning, redness and malodour. The following signs will be evaluated by investigators on a 0-4 point Likert scale (0 = no sign; 1 = mild sign; 2 = moderate sign; 3 = severe sign; 4 = very severe sign): erythema, local warmth, swelling, purulent secretion.	2 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with clinical success at Day 7, Day 28, and Day 42	Clinical success is defined as resolution/improvement of signs and symptoms of infection of the wound in the target lesion	Day 7, Day 28, and Day 42
Time to resolution of all signs and symptoms of infection	It is defined as the disappearance (score = 0) of all signs and symptoms of infection of the wound in the target lesion;	7 weeks
Eradication of the pathogen isolated at the screening visit	Bacteriological success of the wound in the target lesion at Day 14 (V4) and Day 42 (V6).A bacteriological success is defined as eradication of the pathogen isolated at the screening visit, without superinfection or reinfection with the same pathogen;	7 weeks
Changes from baseline to any post-baseline time-point of the size of the target lesion		7 weeks
Global assessment of the target lesion at Day 14 and Day 42	Investigators will be requested to score the outcome of the target lesion on a five-grade scale: 1= worsening, 2 = no change, 3 = minimal improvement, 4 = moderate improvement and 5 = good improvement/resolution;	7 weeks
Changes from baseline to any post-baseline time-point in body temperature		7 weeks
Changes in WBCs count	Changes from baseline to Day 14 (V4) and Day 42 (V6) of white blood cells count (a laboratory parameters that is indicative of infection)	7 weeks
Changes in Erythrocyte sedimentation rate	Changes from baseline to Day 14 (V4) and Day 42 (V6) of ESR values (a laboratory parameters that is indicative of infection)	7 weeks
Changes in High-sensitivity C-reactive protein	Changes from baseline to Day 14 (V4) and Day 42 (V6) of hs-CRP values (a laboratory parameters that is indicative of infection)	7 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects experiencing treatment-emergent adverse events and serious TEAEs		7 weeks
Number of subjects experiencing local TEAEs in the site of application of the IP		7 weeks
Changes from baseline to any post-baseline time point in blood pressure	Systolic and diastolic blood pressure will be measured at each study visit in sitting position after at least 10 minutes rest	7 weeks
Changes from baseline to any post-baseline time point in heart rate	Heart rate will be recorded at each study visit; it will be measured for one minute just prior to the sitting blood pressure measurement.	7 weeks
Changes in haemoglobin values	Haematology will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in haematocrit values	Haematology will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in red blood cell (RBC) count	Haematology will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in platelet count	Haematology will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in creatinine values	Blood chemistry will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in blood urea nitrogen (BUN) values	Blood chemistry will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in glucose values	Blood chemistry will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in aspartate aminotransferase (AST) values	Blood chemistry will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in alanine aminotransferase (ALT) values	Blood chemistry will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in gamma-glutamyl transpeptidase (gamma-GT) values	Blood chemistry will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in alkaline phosphatase values	Blood chemistry will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in total bilirubin values	Blood chemistry will be evaluated in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in sodium values	Electrolytes will be evaluated in blood in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in potassium values	Electrolytes will be evaluated in blood in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in magnesium values	Electrolytes will be evaluated in blood in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in chloride values	Electrolytes will be evaluated in blood in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks
Changes in calcium values	Electrolytes will be evaluated in blood in the reference local laboratory of each investigational study site at the screening visit (Visit 1, Day -7/-3) and at Visit 4 (Day 14) and Visit 6 (Day 42).	7 weeks

Collaborators and Investigators

• Sponsor: Società Scientifica Internazionale di Ossigeno Ozono Terapia
• Investigators: Principal Investigator: Antonio Guastafierro, Pineta Grande Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: March 5, 2021
• First Posted (Actual): March 8, 2021

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Infection; Orthopaedic device
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: sOO3T1 Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No