Clinical Implications of Biofilm in Chronic Wound

NCT ID: NCT05054244

Last Updated: 2022-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Total Enrollment

140 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-07-01

Study Completion Date

2024-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Chronic wounds are important economic and health-care problem. Biofilm has been recognized as a major factor in wound chronicity, delayed healing, and persistent infections, increasing the need for frequent dressing changes, painful debridement and systemic antimicrobial treatments influencing quality of life. In the presence of "un-cultivating" bacteria and limitations of clinical indicators of biofilm presence, there is a need for simple "screening" diagnostic method for biofilm detection. Chronic wounds of different etiology often associated with chronic pain reduce working abilities and cause restrictions in everyday living diminishing patient's quality of life. Efficacy of hyperbaric oxygenation therapy (HBOT) in treating chronic wound and associated infection has been suggested. This observational prospective cohort study will be conducted at the Department of undersea and hyperbaric medicine and Department of dermatovenereology, Clinical Hospital Center Rijeka during 3-year period from 2021. to 2024. including all patients treated due to chronic wound irrespective of the ethology. The patients will be evaluated upon enrolment, after 2, 4, 6 weeks, and 3, 6, 9, 12 months period, to clinically evaluate the wound characteristics, evaluate clinical healing rate, clinical indicators of biofilm and/or infection, need for additional diagnostic or treatment procedures. The patients in both groups (control and HBOT group) will be treated with standard treatment (dressings, debridement, antibiotics, infection control), in addition HBOT sessions will be performed (HBOT group). Impact of chronic wound and both treatment options to patient related outcome measures will be evaluated assessing intensity and pain characteristics, quality of life, depression, and anxiety by means of standardized questionnaires (visual analogue scale, McGill Pain questionnaire, Wound Quality of Life Index, Health Quality of Life Questionnaire, Beck depression and anxiety inventory). Microbiological analyses of swabs/biopsies will be evaluated to determine microbial profile and resistance. Detection and objectivization of biofilm will be evaluated by standard methods on microbiological isolates (Congo red agar, tube method, tissue culture plate method) and confocal scanning laser microscopy, and on clinical samples by light microscopy. Primary and secondary objective will be assessed after 1 year follow-up.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Observational prospective clinical study will be conducted at the Department of undersea and hyperbaric medicine and Department of Dermatovenereology, Clinical Hospital Center Rijeka, Rijeka, Croatia during the 3-year period, from 2021. to 2024. The study will include all patients treated due to chronic wound irrespective of the wound ethology (arterial, diabetic, venous, decubital, combined etiology, posttraumatic, postamputation, burn, and other), 18 years of age and older, that signed informed consent. The patients will be treated with standard methods, i.e., dressings, debridement, antibiotics, and bacterial load relief (control group) and another group will be additionally treated with HBOT (HBOT group). Exclusion criteria of the study is failure to meet one of the inclusion criteria. The patients with contraindications for HBOT, absolute or relative, patients on bleomycin chemotherapy, with chronic obstructive pulmonary disease, previous spontaneous pneumothorax, chronic otitis media or chronic sinusitis, unstable angina pectoris, severe heart failure, severe dementia, history of seizures, claustrophobia, or significant macroangiopathy with absent both distal pulses and no positive response following oxygen provocation test on transcutaneous oximetry that will not benefit from HBOT.

The sample size has been calculated based on the available formula for comparing two independent groups according to qualitative variables with 95% confidence interval. Total sample size in both groups was estimated to be 62 patients (124 patients in total) with expected average of 10-15% patients to drop-out from the study, so calculated total sample size in both groups was estimated to be 70 patients (140 patients in total). Wound healing rate of 90% and higher is expected to be achieved in HBOT group, while expected healing rate in control group is expected to be at least 20% lower after 1 year follow-up. Correspondingly, the same differences are expected to be achieved in control and HBOT group as regarding manifestations of clinical indications of biofilm presence, clinical and laboratory signs of infections.

The patients will be enrolled in the study following eligibility screen, informed consent, collection of patients history and demographic data (age, gender, marital status, children, education level, profession, employment) with special emphasizes to comorbidities and risk factors (diabetes mellitus, obesity, hypertension, cardiovascular diseases, peripheral arterial diseases) physical examination, clinical wound assessment and evaluation including following: wound number; wound location; wound size (width, length and depth in cm, and calculated wound surface in cm2 and wound volume in cm3); wound duration (days); type of the wound (arterial, diabetic, venous, decubital, combined etiology, other); wound status (stagnant, deteriorating, improving, healed); clinical signs of wound infection (heat/warmth, erythema, increased exudate, purulent exudate, increased pain, discolored granulation tissue, friable granulation tissue, oedema, wound foul odour, delayed healing, suspected biofilm; clinical indications of wound biofilm presence (excessive moisture and wound exudate, low-level of erythema, low-level of chronic inflammation, history of antibiotic failure even with appropriate antibiotic or antimicrobial treatment, cycles of recurrent infection/exacerbation, delayed healing, recalcitrant wound to antimicrobial or antibiotic treatment); wound bed status (approximate % of tissues present in the wound bed rated as necrotic, sloughy, granulation, suspected biofilm, epithelialization); exudate level (level, type); condition of surrounding skin (healthy, macerated, dry/eczematous); photo-documentation upon enrolment and at every follow-up according to the protocol. Additional diagnostic procedures will be performed to assess vascular status of the patient and identify the underlying pathophysiology of the wound and the wound type (pulse palpation, Ankle-brachial Pressure Index, toe pressure and radiological imaging, including duplex Doppler ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) imaging, transcutaneous oximetry), as well as laboratory examination, swabs/biopsies for microbiological examination. Upon enrollment, routine laboratory work-up (C-reactive protein, complete and differentiate blood count, serum interleukin-6 and pro-calcitonin level, fasting blood glucose, glycosylated hemoglobin, kidney, and liver tests) and wound swabs/biopsy for microbiological analyses will be performed, and repeated as indicated during follow-up period due to clinically suspected signs of infection.

The patients in control groups will be evaluated upon enrolment, after 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months period, and in HBOT group after 10, 20, 30 treatments, 3 months, 6 months, 9 months, 12 months, for clinical wound assessment and evaluation, and to evaluate the wound healing rate and status, perform wound assessment, record clinical indications of biofilm presence and/or signs of infection, laboratory findings, wound characteristics, the need for antibiotic treatment and hospitalization and perform photo-documentation.

The patients in both groups will be treated routinely with standard treatment (dressings, debridement, antibiotics, and bacterial load relief). The dressing will be performed according to wound characteristics with change every two days including primary dressing (alginates, hydrofiber dressing, antimicrobial dressing, gelling fiber dressing), with silver if infected, and secondary protective dressing (foam with polyurethane) in wounds with formed granulation tissue. The progression of the wound and the need for specific treatment will be evaluated and recorded weekly by dermatologist and vascular surgeon specializing in wound care, and appropriate treatment conducted according to wound assessment (antibiotics, bandage, dressing change, debridement, amputations).

In HBOT group, in addition to standard treatment, the HBOT sessions will be performed 5 days a week, in multi-place chamber at 2.4 atm absolute (ATA) and 100% O2 with effective treatment lasting for 90 min. The sessions will be supervised by doctors trained in hyperbaric medicine.

Impact of chronic wound and both, standard and combined treatment, to patient related outcome measures will be evaluated assessing intensity and pain characteristics, quality of life, depression, and anxiety by means of standardized questionnaires. Intensity and characteristics of pain will be evaluated using self-assessment scales for evaluating pain: visual analogue scale -VAS (measured while dressings are in situ, at dressing change, during debridement, 30 min after dressing change or debridement), and McGill Pain questionnaire upon enrolment, after 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months period. Questionaries for evaluating quality of life and overall health state of patient will be performed upon enrolment, after 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months period including: Wound Quality of Life Index (Wound-QoL) and Health Quality of Life Questionnaire (EQ-5D), and questionaries for evaluating depression and anxiety (Beck depression inventory, Beck anxiety inventory) will be performed upon enrolment, after 6 weeks, 3 months, 6 months, 9 months, 12 months period.

Additionally, microbiological analyses of swabs/biopsies will be evaluated using standardized, routine microbiological, cultural, and automatized procedures, to determine microbial profile, differences, and microbial resistance. In addition, detection and objectivization of biofilm will be evaluated using standard methods for biofilm detection (Tissue culture plate method, Congo red agar method, Tube method), confocal scanning laser microscopy (using FilmTracer LIVE/DEAD fluorescence assay and FilmTracer SYPRO Ruby Biofilm Matrix stain, Invitrogen), and on clinical samples, by light microscopy and different staining methods and procedures (Gram stain, Giemsa stain, Crystal violet stain, Congo red stain, Periodic acid-Schiff stain, Hematoxylin and eosin stain).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Wound Biofilm Chronic Pain Quality of Life Wound Healing

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

control group

The patients in control group will be evaluated upon enrolment, after 2, 4, 6 weeks, 3, 6, 9, and 12 months, to evaluate the wound characteristics, clinical healing rate and indicators of biofilm and/or infection. The patients will be treated with standard treatment (dressings, debridement, antibiotics and infection control). The dressing will be performed according to wound characteristics with change every two days including primary dressing (alginates, hydrofiber dressing, antimicrobial dressing, gelling fiber dressing), with silver if infected, and secondary protective dressing (foam with polyurethane) in wounds with granulation tissue. The patient related outcome measures will be evaluated assessing intensity and pain characteristics, quality of life, depression, and anxiety by means of standardized questionnaires: visual analogue scale, McGill Pain questionnaire, Wound Quality of Life Index, Health Quality of Life Questionnaire, Beck depression and Beck anxiety inventory.

standard wound treatment

Intervention Type OTHER

Standard treatment includes dressings, debridement, antibiotics, and bacterial load relief. The dressing will be performed according to wound characteristics with change every two days including primary dressing (alginates, hydrofiber dressing, antimicrobial dressing, gelling fiber dressing), with silver if infected, and secondary protective dressing (foam with polyurethane) in wounds with formed granulation tissue. The progression of the wound and the need for specific treatment will be evaluated weekly by dermatologist and vascular surgeon specializing in wound care, and appropriate treatment conducted according to wound assessment (antibiotics, bandage, dressing change, debridement, amputations).

HBOT group

The patients in HBOT group will be evaluated upon enrolment, after 2, 4, 6 weeks, 3, 6, 9, and 12 months, to evaluate the wound characteristics, clinical healing rate and indicators of biofilm and/or infection. The patients will be treated with standard treatment (dressings, debridement, antibiotics and infection control). The dressing will be performed according to wound characteristics with change every two days including primary dressing (alginates, hydrofiber dressing, antimicrobial dressing, gelling fiber dressing), with silver if infected, and secondary protective dressing (foam with polyurethane) in wounds with granulation tissue.

The HBOT sessions will be performed 5 days a week in multi-place chamber at 2.4 atm absolute (ATA) and 100% O2. The patient related outcome measures will be evaluated assessing intensity and pain characteristics, quality of life, depression, and anxiety by means of standardized questionnaires as in control group.

standard wound treatment

Intervention Type OTHER

Standard treatment includes dressings, debridement, antibiotics, and bacterial load relief. The dressing will be performed according to wound characteristics with change every two days including primary dressing (alginates, hydrofiber dressing, antimicrobial dressing, gelling fiber dressing), with silver if infected, and secondary protective dressing (foam with polyurethane) in wounds with formed granulation tissue. The progression of the wound and the need for specific treatment will be evaluated weekly by dermatologist and vascular surgeon specializing in wound care, and appropriate treatment conducted according to wound assessment (antibiotics, bandage, dressing change, debridement, amputations).

Hyperbaric oxygenation (HBOT)

Intervention Type PROCEDURE

The HBOT sessions will be performed 5 days a week, in multi-place chamber at 2.4 atm absolute (ATA) and 100% O2 with effective treatment lasting for 90 min. The sessions will be supervised by doctors trained in hyperbaric medicine.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

standard wound treatment

Standard treatment includes dressings, debridement, antibiotics, and bacterial load relief. The dressing will be performed according to wound characteristics with change every two days including primary dressing (alginates, hydrofiber dressing, antimicrobial dressing, gelling fiber dressing), with silver if infected, and secondary protective dressing (foam with polyurethane) in wounds with formed granulation tissue. The progression of the wound and the need for specific treatment will be evaluated weekly by dermatologist and vascular surgeon specializing in wound care, and appropriate treatment conducted according to wound assessment (antibiotics, bandage, dressing change, debridement, amputations).

Intervention Type OTHER

Hyperbaric oxygenation (HBOT)

The HBOT sessions will be performed 5 days a week, in multi-place chamber at 2.4 atm absolute (ATA) and 100% O2 with effective treatment lasting for 90 min. The sessions will be supervised by doctors trained in hyperbaric medicine.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* all patients with chronic wound
* chronic wound irrespective of the ethology (arterial, diabetic, venous, decubital, combined etiology, posttraumatic, postamputation, burn, and other)
* 18 years of age and older
* signed informed consent

Exclusion Criteria

* patients with absolute or relative contraindications for HBOT
* patients on bleomycin chemotherapy
* patients with chronic obstructive pulmonary disease, previous spontaneous pneumothorax, chronic otitis media or chronic sinusitis, unstable angina pectoris, severe heart failure, severe dementia, history of seizures, claustrophobia
* patients with significant macroangiopathy and absent both distal pulses and no positive response following oxygen provocation test on transcutaneous oximetry
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Rijeka

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Tanja Batinac

Associate Prof. M.D. PhD.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Tanja Batinac, M.D., PhD.

Role: PRINCIPAL_INVESTIGATOR

Department of undersea and hyperbaric medicine

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Department of undersea and hyperbaric medicine

Rijeka, , Croatia

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Croatia

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Tanja Batinac, M.D, PhD.

Role: CONTACT

+385915833817

Vlatka Sotošek, M.D., PhD.

Role: CONTACT

+385915986191

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Tanja Batinac, M.D.,PhD.

Role: primary

+385915833817

Role: backup

+38551497435

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

uniri-pr-biomed-19-7-1488

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.