Kerecis Omega3 Wound Plus SOC vs. SOC Alone in Treating Severe Diabetic Foot Ulcers and Forefoot Amputations

Study Overview
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Brief Summary
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This is a prospective, multi-national, multi-centre, randomized, non-blinded (photo evaluation is blinded), controlled clinical investigation in patients suffering from diabetic wounds reaching to tendon, bone, or joint. Patients will be randomised to received intact fish skin (Kerecis™ Omega3 Wound) plus standard of care or standard of care alone, and wound healing compared over 16 weeks.

Detailed Description
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This study is a multi-center study in France, Germany, Italy, and Sweden on the healing effect of Kerecis™ Omega3 Wound in severe diabetic ulcers and open amputation wounds compared to standard of care treatment. Cell and/or tissue based wound treatment products (CTPs) have been advancing in the treatment of non-healing ulcers in the last 20 years. In 2013, a new product was approved in Europe and by the FDA, intact fish skin, delivered as a sterilized, freeze-dried material, for the treatment of acute and chronic wounds. Fish skin has the benefit of not requiring treatment with antibiotics, or virus inactivating methods, thereby allowing the natural content of the skin to remain, and is a by-product of food industry. Therefore, the fish derived CTP is both ecologically sustainable as well as rich in naturally occurring soluble molecules and omega-3 fatty acids. A study evaluating the prognosis of diabetic ulcers from large registry data found that the deeper, larger, and more long-standing ulcers would take longer to heal. If a wound was older than 2 months, larger than 2 cm2 and reached bone or tendon, the likelihood of healing in 20 weeks was 19%. The average cost to close a diabetic foot wound with advanced moist wound healing has been calculated at €2300 per cm2, so closing a 3 cm2 wound would cost €6900.. A wealth of clinical experience on diabetic wounds exists on the Kerecis fish skin material. This is, however, mainly in the form of case series and has been published through posters and case reports. The main indication for Kerecis is deep or non-healing diabetic ulcers, which are the biggest problem in diabetic wound care ultimately leading to amputation. Studies on CTPs have almost solely been done on shallow diabetic ulcers to get a homogeneous study population which then is randomized to treatment with the studied product or the control product. This means that in the case of a favourable outcome in the study, those products are not really tested on the ulcer for which they are ultimately intended, ulcers where the next step is amputation. This randomized controlled study on deep diabetic wounds is designed to prove the efficacy of Kerecis™ Omega3 Wound for the indications it is intended for - severe diabetic foot ulcers - and to show the cost effectiveness of using Kerecis™ Omega3 Wound over standard of care. Wounds resulting from an amputation that are left open with an opening into bone, or from a dehisced amputation where the sutures have gone up, are included. Acute amputations where the metatarsal bones are exposed are included, provided that the patient has diabetes and the amputation is a result of an ulcer. This study is probably the first study on severe diabetic ulcers where the CTP is used on the types of wounds that it is intended for, thereby giving a straight answer to the actual savings included in healing a serious diabetic wound earlier or changing the stage to a smaller shallower ulcer (changing grade of ulcer), thus, radically changing the prognosis.

Official Title
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An Open Label, Randomized Controlled Study to Compare Healing of Severe Diabetic Foot Ulcers and Forefoot Amputations in Diabetics With and Without Moderate Peripheral Arterial Disease Treated With Kerecis Omega3 Wound and SOC vs. SOC Alone

Conditions
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Diabetic Foot Ulcer, Dehiscence of Amputation Stump, Amputation

Intervention / Treatment
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* Device: Kerecis™ Omega3 Wound
* Other: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetic patient with chronic lower extremity wounds: Grade 2 or 3 according to University of Texas score: Grade 2: Wounds that penetrate to tendon or capsule. Grade 3: wounds that penetrate to bone or into the joint. In this context, probing gently to bone means that the wound reaches bone. OR patients with diabetes that are recently amputated below the ankle, where the wound has not been closed or has dehisced and bones/tendons are exposed. Patients that have moderately decreased or normal arterial circulation. In this study the cutoff point is Ankle Brachial Index (ABP) below 0.6. (Toe pressure and TPCO2 values will be obtained if possible. Toe pressure of 50mmHg and a TCPO2 value of 40mm on the dorsum of the foot is often considered as indicative of adequate perfusion.) Patients who will tolerate aggressive debridement. Light bleeding of the wound surface should be seen after debridement. Patient has had his/her ulcer for one month. Participant is willing and able to give informed consent for participation in the clinical trial. Male or Female, over 18 years. Geographical distance compatible with taking part in the study. Observe though that the patient can be treated at a home clinic every other week as long as the end point is not imminent and photos and acetate tracers with cm markers are fed into the photo portal. Negative pregnancy test for a woman of childbearing age. Patient is able (in the investigator's opinion) and willing to comply with all the clinical trial requirements. Exclusion Criteria: Patient whose wound surface is not measurable. Patients suffering from unmanaged osteomyelitis. With adequate treatment the patient can be re-screened for the study. Patient with severe ischemia (Ankle Brachial Index (ABI) <0.6). Patient with necrotic wound who will not tolerate aggressive debridement. Patient with immune deficiency or autoimmune disease. Patients having done arterial reconstruction within one month. These patients can be re-screened later. Patient on systemic corticosteroids or other treatments causing delayed wound healing. Female participants who are pregnant, breast feeding or planning pregnancy during the course of the clinical trial. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the clinical trial, or may influence the result of the clinical trial, or the participant's ability to participate in the clinical trial. Patient with known allergy to fish. Patient deprived of liberty by judicial or administrative decision, person subject to a legal protection measure.

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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No

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: Patients will be randomised to receive either Kerecis™ Omega3 Wound plus standard of care, or standard or care alone.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kerecis™ Omega3 Wound<br> | Device: Kerecis™ Omega3 Wound<br>* Kerecis™ Omega3 Wound is decellularised, intact fish skin from North Atlantic cod fish. Kerecis™ Omega3 Wound is FDA approved and EU cleared for the treatment of diabetic ulcers, chronic vascular ulcers, venous ulcers, trauma wounds (including abrasions, lacerations, and skin tears), acute surgical wounds (including debridement, amputation, and donor sites), surgical wounds (dehiscence or failed healing after surgery), imminent failure of STSG, and post-injection necrosis.<br>|
| Active Comparator: Standard of care<br> | Other: Standard of care<br>* Standard of care wound treatment as defined by the local site, including debridement of the wound, standard wound dressing, and proper offloading of the wound site.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound healing at Week 16 | Percentage of patients with complete wound epithelialisation at 16 weeks as assessed from photographs by a blinded assessor | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ulcer grade | Change in grade of ulcer according to the University of Texas diabetic wound classification at each weekly visit | 16 weeks | 
| Change in quality of life | Change in quality of life as assessed by a Wound Quality of Life questionnaire at each weekly visit. The questionnaire contains 17 questions about the patients' wounds and patients will be asked to rate between five values (e.g. Does your wound hurt? Available answers: not at all, a little, moderately, quite a lot, and very much). | 16 weeks | 
| Change in pain | Pain will be assessed by a visual analogue scale (VAS) at each weekly visit. The VAS will range from 0-10, with 0 being no pain at all, and 10 being worst pain imaginable, and patients will be asked to self-evaluate the pain they experience. | 16 weeks | 
| Healing trajectory | Healing trajectories will be plotted via the change in wound surface area in cm2, vs original wound size, calculated at each weekly visit | 16 weeks | 
| Cost effectiveness | Better cost-effectiveness than standard of care as calculated by global cost of wound treatment of the two arms and projected costs for non-healed ulcers | 16 weeks | 
| Number of participants with fully healed ulcers at 20 weeks | The number of patients with wounds with complete epithelialisation at 20 weeks will be calculated for each arm (checkpoint only) | 20 weeks | 
| Number of participants with fully healed ulcers at 24 weeks | The number of patients with wounds with complete epithelialisation at 24 weeks will be calculated for each arm (checkpoint only) | 24 weeks | 
| Percentage of ulcers healed 50% or more at 12 weeks | The percentage of ulcers healed 50% or more at 12 weeks will be compared between groups. 50% healing indicates epithelialisation of 50% of the original wound area in cm2. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic foot ulcer, DFU, Dehisced amputation, Acute amputation, Fish skin, Kerecis