Clinical trial NCT04787575: Oxygen-ozone Therapy Plus Antibiotic Therapy in the Treatment of Infections Secondary to Implant of Orthopaedic Devices
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infection
Keywords: Infection
Orthopaedic device
Lead sponsor: Società Scientifica Internazionale di Ossigeno Ozono Terapia
Sponsor class: OTHER
First posted: 2021-03-08
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, multicentre, randomized, parallel group study
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical success at Day 14
timeFrame: 2 week
Secondary outcomes:
measure: Proportion of patients with clinical success at Day 7, Day 28, and Day 42
timeFrame: Day 7, Day 28, and Day 42
measure: Time to resolution of all signs and symptoms of infection
timeFrame: 7 weeks
measure: Eradication of the pathogen isolated at the screening visit
timeFrame: 7 weeks
measure: Changes from baseline to any post-baseline time-point of the size of the target lesion
timeFrame: 7 weeks
measure: Global assessment of the target lesion at Day 14 and Day 42
timeFrame: 7 weeks
measure: Changes from baseline to any post-baseline time-point in body temperature
timeFrame: 7 weeks
measure: Changes in WBCs count
timeFrame: 7 weeks
measure: Changes in Erythrocyte sedimentation rate
timeFrame: 7 weeks
measure: Changes in High-sensitivity C-reactive protein
timeFrame: 7 weeks
Other outcomes:
measure: Number of subjects experiencing treatment-emergent adverse events and serious TEAEs
timeFrame: 7 weeks
measure: Number of subjects experiencing local TEAEs in the site of application of the IP
timeFrame: 7 weeks
measure: Changes from baseline to any post-baseline time point in blood pressure
timeFrame: 7 weeks
measure: Changes from baseline to any post-baseline time point in heart rate
timeFrame: 7 weeks
measure: Changes in haemoglobin values
timeFrame: 7 weeks
measure: Changes in haematocrit values
timeFrame: 7 weeks
measure: Changes in red blood cell (RBC) count
timeFrame: 7 weeks
measure: Changes in platelet count
timeFrame: 7 weeks
measure: Changes in creatinine values
timeFrame: 7 weeks
measure: Changes in blood urea nitrogen (BUN) values
timeFrame: 7 weeks
measure: Changes in glucose values
timeFrame: 7 weeks
measure: Changes in aspartate aminotransferase (AST) values
timeFrame: 7 weeks
measure: Changes in alanine aminotransferase (ALT) values
timeFrame: 7 weeks
measure: Changes in gamma-glutamyl transpeptidase (gamma-GT) values
timeFrame: 7 weeks
measure: Changes in alkaline phosphatase values
timeFrame: 7 weeks
measure: Changes in total bilirubin values
timeFrame: 7 weeks
measure: Changes in sodium values
timeFrame: 7 weeks
measure: Changes in potassium values
timeFrame: 7 weeks
measure: Changes in magnesium values
timeFrame: 7 weeks
measure: Changes in chloride values
timeFrame: 7 weeks
measure: Changes in calcium values
timeFrame: 7 weeks
Locations:
city: Castel Volturno
country: Italy
facility: Pineta Grande Hospital
state: Caserta
city: Ancona
country: Italy
facility: Ospedali Riuniti Torrette
city: Napoli
country: Italy
facility: Università Federico II
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone di Palermo
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Casa Di Cura Citta' Di Roma
Study officials:
affiliation: PINETA GRANDE HOSPITAL
name: Antonio Guastafierro
role: PRINCIPAL_INVESTIGATOR
References: