Violet-Blue Light Inactivation of Bacteria in Chronic Wounds

Study Overview
=================
Brief Summary
-----------------
This four-week prospective clinical investigation will assess the safety and feasibility of a medical device without CE-marking. The medical device is a light-emitting-diode (LED) and is manufactured by VulCur MedTech Aps. Violet-blue light treatment is tested on a total of twenty-two patients with chronic wounds, divided into three groups, each group only receiving one dosage. Three dosages (low, medium and high) of violet-blue light treatment is tested. ID 1-7 are assigned to the low group, ID 8-15 are assigned to medium group and ID 16-22 are assigned to the high dosage group.

Detailed Description
-----------------
This is as prospective safety and feasibility clinical trial investigating violet-blue light treatment on chronic wounds. This clinical trial runs from Q3 2022 - Q2 2023. Twenty-two patients with chronic wounds will be included (n = 22) for a study-period of four weeks. Week 1 includes one baseline visit. Through Week 2,3 and 4 treatment is given six times with a span of 24-72 hours between every treatment visit. Week 4 includes one follow up-visit. Patients entering the study are assigned to three light dosage groups (low, medium and high) according to their study ID. ID 1-7 are assigned to the low group, ID 8-15 are assigned to medium group and ID 16-22 are assigned to the high dosage group. Between each dosage of light, there will be an evaluation of primary and secondary endpoints by the sponsor and the principal investigator. Light dosage is only escalated should this evaluation be deemed safe. To determine treatment safety skin reactions are assessed after treatment at: 0 minutes, 30 minutes, 24 hours, 48 hours, 5th treatment visit and at follow-up. Adverse Events and Adverse Device Events are evaluated at every visit for every dosage, feasibility is evaluated at follow-up for both patient and investigator. This investigation complies with the Good Clinical Practice concerning medical devices and follows the ISO standard DS/EN 14 155 and the Declaration of Helsinki

Official Title
-----------------
Violet-Blue Light Inactivation of Bacteria in Chronic Wounds

Conditions
-----------------
Phototherapy Complication, Photobiology, Light Treatment; Complications, Wound Infection, Wound Heal

Intervention / Treatment
-----------------
* Device: Violet-Blue Light Treatment / FlashHeal Device


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men, women and non-binaries fulfilling all inclusion criteria Age >18 - Patients with a chronic wound defined > 6 weeks Wound Area > 1 cm and < 25 cm Patient can understand Danish Patient can comply with protocol Patient is fully informed about the study and has given informed consent Exclusion Criteria: Clinical infection in the wound requiring systemic or local antibiotics Current intake of antibiotics or locally applied (within 7 days before baseline) Known or suspected cancer in the wound Previous Photodermatitis and/or Photosensitivity Previous Porphyria and/or hypersensitivity to porphyrins Known congenital or acquired immunodeficiency Newly adjusted or newly started systemic immunomodulate treatment >4 weeks Treatment with haemodialysis Dementia - Participating in other clinical wound healing studies in the last 30 days Judgement by the investigator that the patient is not suited for study participation Pregnant or breastfeeding women. (All fertile women who is not on safe contraception will need a negative pregnancy test performed at baseline. Safe contraception includes cobber and hormone Intra Uterine Device and Hormone anticonception drugs. Sterility is defined as have had surgical sterilisation and being postmenopausal)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Device Feasibility
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This four-week prospective clinical investigation will assess the safety and feasibility of a medical device emitting LED violet-blue light. Violet-blue light treatment is tested on a total of twenty-two patients with chronic wounds, divided into three groups, each group only receiving one dosage. Three dosages (low, medium and high) of violet-blue light treatment is tested. ID 1-7 are assigned to the low group, ID 8-15 are assigned to medium group and ID 16-22 are assigned to the high dosage group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Exposure to Violet-Blue Light<br>ID 1-7 are assigned to the low dosage group | Device: Violet-Blue Light Treatment / FlashHeal Device<br>* FlashHeal illuminates an area of 10 cm in diameter, located at 6-7 cm distance of the wound. Wounds larger than 10 cm in diameter, will receive enough treatments to cover the wound bed. To obtain full coverage the circular treatment area is relocated to cover the remaining wound field. The wavelength is 405 nm, Full Width Half Maximum at (FWHM) 400-415 nm. Device irradiances are adjusted to the total fluences required for the Low, Medium and High group, the treatment will last 15 minutes at all dosages. Light is emitted with 1000 Hz.<br>|
| Experimental: Medium Exposure to Violet-Blue Light<br>ID 8-15 are assigned to the medium dosage group | Device: Violet-Blue Light Treatment / FlashHeal Device<br>* FlashHeal illuminates an area of 10 cm in diameter, located at 6-7 cm distance of the wound. Wounds larger than 10 cm in diameter, will receive enough treatments to cover the wound bed. To obtain full coverage the circular treatment area is relocated to cover the remaining wound field. The wavelength is 405 nm, Full Width Half Maximum at (FWHM) 400-415 nm. Device irradiances are adjusted to the total fluences required for the Low, Medium and High group, the treatment will last 15 minutes at all dosages. Light is emitted with 1000 Hz.<br>|
| Experimental: High Exposure to Violet-Blue Light<br>ID 16-22 are assigned to the high dosage group | Device: Violet-Blue Light Treatment / FlashHeal Device<br>* FlashHeal illuminates an area of 10 cm in diameter, located at 6-7 cm distance of the wound. Wounds larger than 10 cm in diameter, will receive enough treatments to cover the wound bed. To obtain full coverage the circular treatment area is relocated to cover the remaining wound field. The wavelength is 405 nm, Full Width Half Maximum at (FWHM) 400-415 nm. Device irradiances are adjusted to the total fluences required for the Low, Medium and High group, the treatment will last 15 minutes at all dosages. Light is emitted with 1000 Hz.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) | Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE) adjusted to the skin. The violet-blue light treatment will be considered safe when less than 30 % have an overall CTCAE score larger than Grade 2 CTCAE. The overall CTCAE score for each patient is based on the one CTCAE score with the most severe grading. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Clinical Wound Assessment | Evaluates wound symptoms (Exudate, necrosis, maceration, granulation, Oedema,) and skin symptoms (eczema, Erythema, Hyperpigmentation, Hypopogmentation, epthilializing) at a 4 step scale from none to mild, moderate, severe. | Baseline, 1 week | 
| Clinical Wound Assessment | Evaluates wound symptoms (Exudate, necrosis, maceration, granulation, Oedema,) and skin symptoms (eczema, Erythema, Hyperpigmentation, Hypopogmentation, epthilializing) at a 4 step scale from none to mild, moderate, severe. | Pre-intervention, up to 3 weeks | 
| Follow up Clinical Wound Assessment | Evaluates wound symptoms (Exudate, necrosis, maceration, granulation, Oedema,) and skin symptoms (eczema, Erythema, Hyperpigmentation, Hypopogmentation, epthilializing) at a 4 step scale from none to mild, moderate, severe. | Follow Up, up to 4 weeks | 
| Numeric Rating Scale (1-10) | Pain scale in relation to treatment. Higher scores indicate more pain. | Post-intervention, up to 3 weeks | 
| Wong Baker FACES (1-10) | Visual Pain scale in relation to treatment. Higher scores indicate more pain. | Post-intervention, up to 3 weeks | 
| Investigator Questionnaire | Usability of the medical device is tested with the system usability Scale (SUS) testing 10 items on a 5 step scale from Strongly Disagree to Strongly Agree. | 4 weeks | 
| Patient Questionnaire | Evaluating Participant perceived; pain, time consumption and satisfaction through 20 items. Question 1-13 can be answered on a 5 step scale from to a very high degree till not at all, including possibility to answer dont know and not relevant. Item 14-20 can be answered with Yes, No and Dont Know. | 4 weeks | 
| Mean time of visit | Total time for the visit will be measured in minutes. | For every visit, up to 4 weeks | 
| Mean time of Treatment Procedure | For every treatment visit, time used for the treatment with the FlashHeal Device is measured. Time is measured in minutes. | Post-intervention, up to 3 weeks | 
| Baseline Mean Bacterial Load | E-Swabs, Essen Rotary Technique performed at baseline, follow-up and before and after treatment with FlashHeal Device. Bacteria will be cultured for aerobe and anaerobe species. | 1 week | 
| Pre-intervention Mean Bacterial Load | E-Swabs, Essen Rotary Technique performed at baseline, follow-up and before and after treatment with FlashHeal Device. Bacteria will be cultured for aerobe and anaerobe species. | Pre-intervention, up to 3 weeks | 
| Post-intervention Mean Bacterial Load | E-Swabs, Essen Rotary Technique performed at baseline, follow-up and before and after treatment with FlashHeal Device. Bacteria will be cultured for aerobe and anaerobe species. | Post-intervention, up to 3 weeks | 
| Mean Bacterial Load at Follow Up | E-Swabs, Essen Rotary Technique performed at baseline, follow-up and before and after treatment with FlashHeal Device. Bacteria will be cultured for aerobe and anaerobe species. | Follow up, up to 4 weeks | 
| Baseline Wound Fluid | Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment. | Baseline, 1 Week | 
| Change from Baseline Wound Fluid Composition Week 1 to Week 2 | Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment. | 2 Weeks | 
| Change from Baseline Wound Fluid Composition Week 1 to Week 3 | Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment. | 3 Weeks | 
| Change from Baseline Wound Fluid Composition Week 1 to Week 4 | Swab for wound fluid performed once every week using the Essen Rotary Technique, testing for 6-10 cytokines assessing the inflammatory microenvironment. | 4 weeks | 
| Baseline Wound Size Week 1 | Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2. | Baseline, week 1 | 
| Change from Baseline Wound Size Week 1 to Week 2 | Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2. | 2 Weeks | 
| Change from Baseline Wound Size Week 1 to Week 3 | Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2. | 3 Weeks | 
| Change from Baseline Wound Size Week 1 to Week 4 | Clinical Photography is performed once every week. Hereafter the wound is analysed with the ImageJ software to calculate wound size in cm2. | Follow Up, 4 weeks | 
| Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) | Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin. | Post-intervention, 2 weeks | 
| Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) | Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin. | 30 minutes Post-intervention, 2 weeks | 
| Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) | Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin. | 24 hours Post-intervention, 2 weeks | 
| Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) | Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin. | 48 hours Post-intervention, 2 weeks | 
| Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) | Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin. | 120 hours Post-intervention, 2 weeks | 
| Common Terminology Criteria for Adverse Events, version 5.0, Nov 27, 2017 (CTCAE) | Safety is measured as the absence of Adverse Events (AE) skin reactions. Adverse event skin reactions are assessed with the Common Terminology Criteria for Adverse Events U.S Department of Health and Human Services version 5.0, Nov 27, 2017 (CTCAE). The CTCAE is adjusted to the skin. | Follow Up, 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Violet Blue Light, Blue Light, Safety