Antimicrobial Photodynamic Therapy in the Nasal Decolonization of Maintenance Hemodialysis Patients (COLONIZATION)

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency, Chronic; Photochemotherapy
• Intervention / Treatment: Device: Antimicrobial Photodynamic therapy; Drug: Mupirocin ointment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01504-001
    • University of Nove de Julho (UNINOVE)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: control mupirocin group; 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; Performed with 2% Mupirocin Ointment, to be applied to the anterior nostrils twice a day for 5 days.; Other Names: Mupirocin Nasal Product
Experimental: experimental aPDT group; 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; 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; Other Names: Photochemotherapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Nove de Julho
• Investigators: Principal Investigator: Anna Carolina RT Horliana, phD, Nove de Julho University; Principal Investigator: Daniella T Bezerra, phD, Nove de Julho University

Publications and helpful links

General Publications

• Wertheim HF, Melles DC, Vos MC, van Leeuwen W, van Belkum A, Verbrugh HA, Nouwen JL. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis. 2005 Dec;5(12):751-62. doi: 10.1016/S1473-3099(05)70295-4.
• Tacconelli E, Carmeli Y, Aizer A, Ferreira G, Foreman MG, D'Agata EM. Mupirocin prophylaxis to prevent Staphylococcus aureus infection in patients undergoing dialysis: a meta-analysis. Clin Infect Dis. 2003 Dec 15;37(12):1629-38. doi: 10.1086/379715. Epub 2003 Nov 20.
• Fu XJ, Fang Y, Yao M. Antimicrobial photodynamic therapy for methicillin-resistant Staphylococcus aureus infection. Biomed Res Int. 2013;2013:159157. doi: 10.1155/2013/159157. Epub 2013 Feb 28.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): January 15, 2021
• Study Completion (Actual): July 12, 2021

Study Registration Dates

• First Submitted: August 2, 2019
• First Submitted That Met QC Criteria: August 5, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: chronic kidney disease; Staphylococcus aureus; hemodialysis; mupirocin; nasal decolonization; antimicrobial photodynamic therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Synthesis Inhibitors; Anti-Bacterial Agents; Mupirocin; Anti-Infective Agents
• Other Study ID Numbers: NASAL DECOLONIZATION

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