Antimicrobial Photodynamic Therapy in the Nasal Decolonization of Maintenance Hemodialysis Patients

Study Overview
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Brief Summary
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The objective of this study will be to evaluate the effect of Antimicrobial Photodynamic Therapy (aPDT) in the Nasal Decolonization of Dialytic Chronic Renal Patients, Staphylococcus Aureus (S.aureus) Carriers This is a 3-months follow-up, randomized, single-blind, prospective controlled trial, single-center and will happen in 02 phases: Phase 1 - Epidemiological Evaluation - A researcher will invite the research participants who are undergoing treatment at the Hemodialysis Service of Clinical Hospital and explain its contents. After reading and signing the informed consent, this same researcher (calibrated for the experiment) will perform nasal secretion microbiological collections to identify patients colonized by S.aureus in the anterior nostril (nasal carrier) - baseline T0 and the application of the questionnaire that identifies possible factors that may be considered as risk for colonization and possible development of diseases related to S. aureus. In the laboratory of Microbiology, the strains will be identified and the colonized patients will be invited to continue the study (Phase 2). Non-carrier patients will only be counseled with infection prevention care. Phase 2 - Parallel clinical trial with two intervention groups (aPDT or Mupirocin) - Patients with nasal aureus (thirty-four colonized patients aged over 18 years) will be treated with aPDT (experimental group) or mupirocin (control group). A trained researcher will collect new aliquots of nasal discharge after completion of nostril treatment (T1) to check for decolonization by culture. A new collection will be performed at 1 (T2) and 3 (T3) months after treatment to assess recolonization. It was evaluated intervention safety (photodynamic therapy) through a directed and open questionnaire about adverse effects.

Detailed Description
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Infections are the leading cause of morbidity and the second leading cause of mortality among patients with chronic kidney disease (CKD) on renal replacement therapy. Staphylococcus aureus (S. aureus) is a major agent and previous nasal colonization represents an independent risk factor for infection. Up to 50% of these patients can be known to be colonized. With the global increase in bacterial resistance by S.aureus strategies for infection prevention and transmission by this agent are needed. The strategy of decolonization and elimination of nasal carrier status by S.aureus in dialytic chronic renal patients reduces infection rates, especially bacteremia. The gold standard for nasal decolonization is topical mupirocin treatment, but there are reports of increasing resistance especially after prolonged use, which limits the establishment of clinical protocols for the prevention of infection in the dialysis population. Antimicrobial Photodynamic Therapy (aPDT) proves to be a promising approach for its potential bactericidal effect, including multidrug-resistant bacteria and its low tendency to induce drug resistance. This is a 3-months follow-up, randomized, single-blind, prospective controlled trial, single-center and will happen in 02 phases: Phase 1 - Epidemiological Evaluation - A researcher will invite the research participants who are undergoing treatment at the Hemodialysis Service of Clinical Hospital and explain its contents. After reading and signing the informed consent, this same researcher (calibrated for the experiment) will perform nasal secretion microbiological collections to identify patients colonized by S.aureus in the anterior nostril (nasal carrier) - baseline T0 and the application of the questionnaire that identifies possible factors that may be considered as risk for colonization and possible development of diseases related to S. aureus. In the laboratory of Microbiology, the strains will be identified and the colonized patients will be invited to continue the study (Phase 2). Non-carrier patients will only be counseled with infection prevention care. Phase 2 - Parallel clinical trial with two intervention groups (aPDT or Mupirocin) - Patients with nasal aureus (thirty-four colonized patients aged over 18 years) will be treated with aPDT (experimental group) or mupirocin (control group). Two other trained researchers will collect new aliquots of nasal discharge after completion of nostril treatment (T1) to check for decolonization by culture. A new collection will be performed at 1 (T2) and 3 (T3) months after treatment to assess recolonization.It was evaluated intervention safety (photodynamic therapy) through a directed and open questionnaire about adverse effects,immediately after treatments, with a 3-month follow-up.

Official Title
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Antimicrobial Photodynamic Therapy in the Nasal Decolonization of Maintenance Hemodialysis Patients: A Pilot Randomized Trial

Conditions
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Photochemotherapy, Renal Insufficiency, Chronic

Intervention / Treatment
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* Device: Antimicrobial Photodynamic therapy
* Drug: Mupirocin ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: nasal carriers of S.aureus chronic kidney patient undergoing hemodialysis treatment; aged over 18 years; both genders; Exclusion Criteria: pregnancy or breastfeeding; presence of nasal foreign body; history of nasal surgery in the last 3 months; active infection by S. aureus; use of topical nasal or systemic antibiotic in the last three months; history of severe allergy to mupirocin or methylene blue (MB);

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 34 individuals will be randomly divided into 2 groups: G1 - Experimental Group (n = 17) - Treatment will be performed with methylene blue and red light-emitting diode (LED) in the nostrils. G2 - Control group (n = 17) - Standard treatment will be performed conventionally with topical mupirocin.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental aPDT group<br>Application of 0.01% methylene blue with enough sterile swab to cover the inner nostril extension with a 10 minute pre-irradiation time. The irradiations were carried out with a red light-emitting diode (LED) (λ = 660 nm), for 300 seconds, irradiance of 400 mW / cm2, radiant exposure 124 J / cm2, with uniform application in each anterior nostril. | Device: Antimicrobial Photodynamic therapy<br>* Application 0.01% methylene blue with sterile swabs in each nostril with a 10-minute pre-irradiation • Light-emitting diode (λ = 660 nm), for 300 seconds, with an irradiance of 400 mW / cm2<br>* Other names: Photochemotherapy;|
| Active Comparator: control mupirocin group<br>A standard treatment will be performed conventionally with topical mupirocin. Will be performed with 2% Mupirocin Ointment, to be applied to the anterior nostrils twice a day for 5 days. | Drug: Mupirocin ointment<br>* Performed with 2% Mupirocin Ointment, to be applied to the anterior nostrils twice a day for 5 days.<br>* Other names: Mupirocin Nasal Product;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualitative culture (presence or absence bacterial colonies) after aPDT (antimicrobial photodynamic therapy) decolonization or mupirocin | The microbiological analysis was done by MALDI-TOF (Biomérieux) - Matrix Associated Laser Desorption-Ionization - Time of Fligh | Before the intervention (T0) | 
| Qualitative culture (presence or absence bacterial colonies) after aPDT (antimicrobial photodynamic therapy) decolonization or mupirocin | The microbiological analysis was done by MALDI-TOF (Biomérieux) - Matrix Associated Laser Desorption-Ionization - Time of Fligh | Immediately after the completion of treatments (T1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of S.aureus | To evaluate the prevalence of both sensitive and methicillin-resistant S.aureus patients by bacterial culture and antibiogram in patients with renal chronic disease on dialysis treatment at the Hemodialysis Service of the University of São Paulo Medical School of Sao Paulo. | initial screening time to assess nasal staphylococcus aureus carrier before treatments | 
| Prevalence of recolonization | To evaluate the prevalence of recolonization by Staphylococcus aureus in the anterior nostril in through qualitative microbiological culture (presence or absence). The microbiological analysis was done by MALDI-TOF (Biomérieux) - Matrix Associated Laser Desorption-Ionization - Time of Flight. | 01 and 03 months after treatments | 
| Anamnesis and risk factor collection | Guiding questions were applied to all patients. In addition to questions related to the patient's general health, demographic data (age, gender, marital status, occupation, education, housing), medical history data (etiology of CKD ( renal chronic disease), comorbidities, time of dialysis treatment until protocol initiation, presence smoking rate, type of venous access and time of use, kidney transplantation, systemic antibiotic therapy in the last 12 months, hospitalization or infection (including skin) in the last 12 months). | immediately after recruiting and accepting patients who met the inclusion/exclusion criteria | 
| Ontervention safety: photodynamic therapy | The analysis of adverse effects through a directed and open questionnaire, especially for this study | immediately after treatments, with a 3-month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antimicrobial photodynamic therapy, Staphylococcus aureus, nasal decolonization, hemodialysis, chronic kidney disease, mupirocin