Clinical Implications of Biofilm in Chronic Wound

NCT05054244 | Unknown

• 1 other identifier: uniri-pr-biomed-19-7-1488
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Wound; Biofilm; Chronic Pain; Quality of Life; Wound Healing

Keywords

Wound; Biofilm; Chronic pain; Quality of Life; Wound Healing; Hyperbaric oxygenation

Outcome Measures

Primary Outcomes (9)

• wound healing

  In participants of both, control and HBOT group, changes in wound healing from baseline and at 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months will be reported by calculating changes in wound sizes from baseline and evaluation times, based on measured wound width, length, and depth (in cm), measured manually and by high-resolution calibrated digital photographs, and calculated wound surface (expressed in cm2) and wound volume (expressed in cm3). In case of multiple wounds all wounds will be measured. The sizes will be averaged at baseline and at every wound assessment to follow wound progress differences in wound healing or/expanding between baseline and 12-month period will be expressed as binary result. The data at baseline and during follow-up period in both patient groups will be compared.

  1 year of patient follow up

• wound status

  Changes in wound status from baseline and at 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months will be reported in participants of both, control and HBOT group will be recorded in four categories: stagnant, deteriorating, improving, healed. Complete wound healing will be defined by complete epithelization. The number of patients in both groups will be expressed as binary result in all four categories during the follow-up period. The data at baseline and during follow-up period in both patient groups will be compared.

  1 year follow up

• clinical signs of wound infection

  Changes in clinical signs of wound infection from baseline and at 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months in participants of both, control and HBOT group, will be recorded, evaluated as present or absent (yes/no) as follows: heat/warmth, erythema, increased exudate, purulent exudate, increased pain, discolored granulation tissue, friable granulation tissue, oedema, wound foul odour, delayed healing, suspected biofilm. The number of patients in both groups will be expressed as binary result in all categories during follow-up period. The data at baseline and during follow-up period in both patient groups will be compared.

  1 year follow up

• clinical indications of biofilm presence

  Changes in clinical indications of wound biofilm presence during routine clinical wound assessment, from baseline and at 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months in participants of both, control and HBOT group, will be recorded as present or absent (yes/no) as follows: excessive moisture and wound exudate, signs of local infection (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. The number of patients in both groups will be expressed as binary result in all categories during the follow-up period. The data at baseline and during follow-up period in both patient groups will be compared.

  1 year follow up

• laboratory signs of infections

  In participants of both groups, control and HBOT group, changes in laboratory findings of infection as evaluated by concentrations of serum C reactive protein, interleukin-6 and pro-calcitonin, and the number of leukocytes and neutrophiles in peripheral blood from baseline and at 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months, will be recorded. The values of laboratory findings within reference interval will be rated as negative and increased values as positive. The number of patients in both groups will be expressed as binary result in all categories during the follow-up period. The data at baseline and during follow-up period in both patient groups will be compared.

  1 year follow up

• patient related outcome - pain scores in patients with chronic wounds

  In participants of both groups, control and HBOT group, changes in pain scores from baseline and at 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months will be reported on Visual Analogue Scale (VAS). Pain scores will be measured while dressings are in situ, at dressing change, during debridement, 30 min after dressing change or debridement, on scale from 0 representing no pain, to 10, latter corresponding to the worst pain and outcome, and expressed as binary result. The data from questionnaire at baseline and during follow-up period in both patient groups will be compared.

  1 year follow up

• patient related outcome - pain quality and intensity in patients with chronic wounds

  In participants of both groups, control and HBOT group, changes in sensory and affective pain quality and intensity from baseline and at 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months will be measured by means of standardized McGill Pain questionnaire using 4-point Likert-type scale ranging from 0 to 3. The total score ranges from 0 to 45, latter corresponding to the worse outcome. The data from questionnaire at baseline and during follow-up period in both patient groups will be compared.

  1 year follow up

• patient related outcome - unique overall health state in patients with chronic wounds

  In participants of both groups, control and HBOT group, changes in overall patient's health state from baseline and at 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months will be measured by means of standardized questionnaire using Health Quality of Life Questionnaire (EQ-5D), a descriptive system consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and each dimension has five response levels: 1-no problems, 2-slight problems, 3-moderate problems, 4-severe problems, 5-unable to/extreme problems. A patient's health state is defined by combining one level from each of the five dimensions in a 5-digit code. The data from questionnaire at baseline and during follow-up period in both patient groups will be compared.

  1 year follow up

• patient related outcome - quality of life in patients with chronic wounds

  In participants of both groups, control and HBOT group, changes in quality of life from baseline and at 2, 4, 6 weeks, 3 months, 6 months, 9 months, 12 months will be measured by means of standardized questionnaire using the disease-specific, health-related quality of life of patients with chronic wounds, Wound Quality of Life Index Questionnaire (Wound-QoL) that consists of 17 items on impairments assessed in retrospect to the preceding seven days , and scored with 0 to 4 (0='not at all' to 4='very much'). A Wound-QoL global score on overall disease-specific quality of life will be evaluated computed by averaging all items, with minimal score 0 and highest 68, latter corresponding to the worst outcome. The data from questionnaire at baseline and during follow-up period in both patient groups will be compared.

  1 year follow up

Secondary Outcomes (4)

• patient related outcome -depression in patients with chronic wounds

  1 year follow up

• patient related outcome - anxiety in patients with chronic wounds

  1 year follow up

• objectivization of biofilm

  3 years

• clinical screening for the presence of biofilm by light microscopy

  3 years

Study Arms (2)

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.

Other: standard wound treatment

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.

Other: standard wound treatment; Procedure: Hyperbaric oxygenation (HBOT)

Interventions

standard wound treatment 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; control group

Hyperbaric oxygenation (HBOT) 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.

HBOT group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients treated due to chronic wound at Department of undersea and hyperbaric medicine and Department of dermatovenereology, Clinical Hospital Center Rijeka during 3-year period from 2021. to 2024., irrespective of wound ethology, 18 years of age and older. The patients will be treated with standard methods (Control group) and with standard methods+ HBOT (HBOT group).

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Rijeka: lead

Study Sites (1)

Department of undersea and hyperbaric medicine

Rijeka, 51000, Croatia

RECRUITING

MeSH Terms

Conditions

Wounds and Injuries; Chronic Pain

Interventions

Hyperbaric Oxygenation

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Oxygen Inhalation Therapy; Respiratory Therapy; Therapeutics

Study Officials

• Tanja Batinac, M.D., PhD.

  Department of undersea and hyperbaric medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tanja Batinac, M.D, PhD.

CONTACT

+385915833817; tanja.batinac@uniri.hr

Vlatka Sotošek, M.D., PhD.

CONTACT

+385915986191; vlatkast@medri.uniri.hr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Prof. M.D. PhD.

Study Record Dates

• First Submitted: August 16, 2021
• First Posted: September 23, 2021
• Study Start: July 1, 2021
• Primary Completion: December 31, 2022
• Study Completion: June 30, 2024
• Last Updated: November 8, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1)