Fish Skin Graft for Venous Leg Ulcers

(THOR Trial)

Overseen By Thomas Serena, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Kerecis Ltd.

Must not be taking: Immunosuppressants, Chemotherapy, Biologics, others

Disqualifiers: End stage renal disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a unique fish skin graft to heal stubborn venous leg ulcers (VLUs), which are painful sores often caused by poor blood flow in the legs. The study compares the results of using the fish skin graft with standard treatments against using standard treatments alone. It aims to determine if the fish skin graft can close these ulcers more effectively over 12 weeks. Individuals with venous leg ulcers that haven't healed for at least four weeks and haven't shown significant improvement recently might be suitable for this study. As a Phase 4 trial, this research involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressants, high-dose corticosteroids, or chemotherapy, you may not be eligible to participate.

What is the safety track record for the Intact Fish Skin Graft?

Research has shown that the Intact Fish Skin Graft is generally safe and well-tolerated. Studies have found that this treatment speeds up wound healing and enhances the appearance and function of the healed area. No known risks exist for spreading viruses or infectious proteins with this graft, making it a safe option for treating wounds such as venous leg ulcers. Its use in other types of wounds further supports its safety. Overall, users of the fish skin graft have not reported any serious side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatment for venous leg ulcers, which involves cleaning, debridement, moisture balance, and offloading, the fish skin graft offers a unique approach. This treatment uses intact fish skin, known for its natural omega-3 fatty acids, to promote faster healing and reduce inflammation. Researchers are excited about this treatment because the fish skin's structure closely mimics human skin, potentially providing a more effective scaffold for skin regeneration and quicker wound healing.

What evidence suggests that the Intact Fish Skin Graft is effective for venous leg ulcers?

This trial will compare Intact Fish Skin Grafts (IFSG) combined with standard care to standard care alone for treating venous leg ulcers. Studies have shown that Intact Fish Skin Grafts can speed up wound healing and improve appearance. Research indicates that these grafts reduce swelling and irritation due to their anti-inflammatory properties. They are particularly effective for difficult wounds like venous leg ulcers. Patients receiving fish skin grafts often experience faster wound closure compared to those receiving standard treatment alone. Overall, evidence suggests that Intact Fish Skin Grafts offer a promising option for treating venous leg ulcers. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with nonhealing venous leg ulcers present for at least 4 weeks, but not treated with high-level compression for more than a year. The ulcer must be between 1 and 25 cm2 post-debridement. Participants need adequate blood flow as indicated by specific tests (ABI, TBI, TCOM, PVR). Those with multiple ulcers can join if the largest one meets these conditions.

Inclusion Criteria

My TBI score is 0.6 or higher.

I have a leg ulcer that hasn't healed in over 4 weeks and haven't had long-term compression treatment.

My wound has not visibly improved or shrunk by 40% in the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Intact Fish Skin Graft plus standard of care or standard of care alone for nonhealing venous leg ulcers

12 weeks

Up to 12 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intact Fish Skin Graft

Trial Overview

The study aims to see if adding Intact Fish Skin Graft (IFSG) to standard wound care helps heal tough venous leg ulcers better than just standard care alone. Patients are split into two groups: one receives IFSG/SOC and the other only SOC, and their healing progress is compared over a period of 12 weeks.

How Is the Trial Designed?

Group I: Intact Fish Skin Graft (IFSG) + Standard of Care Experimental Treatment 1 Intervention

Up to 12 visits with Intact Fish Skin Graft (IFSG) + Standard of Care.

Group II: Standard of Care Active Control 1 Intervention

Standard of care will be cleaning, debridement, ulcer moisture balance, and offloading.

Intact Fish Skin Graft is already approved in European Union, United States for the following indications:

Approved in European Union as Kerecis Omega3 for:

• Second-degree burn wounds
• Chronic wounds
• Venous leg ulcers
• Diabetic foot ulcers

Approved in United States as Kerecis Omega3 for:

• Second-degree burn wounds
• Chronic wounds
• Venous leg ulcers
• Diabetic foot ulcers

Who Is Running the Clinical Trial?

Kerecis Ltd.

Lead Sponsor

Trials

14

Recruited

2,200+

Serena Group

Collaborator

Trials

6

Recruited

790+

Serena Group

Collaborator

Trials

6

Recruited

790+

Published Research Related to This Trial

In a study of eight diabetic patients with postoperative foot wounds, the use of an intact fish skin graft rich in omega-3 resulted in over 84.9% reduction in wound area for wounds less than three months old after six weeks of treatment.

No infections or adverse skin reactions were reported, indicating that the fish skin graft is safe and may be an effective adjunct treatment for accelerating healing in diabetic foot wounds, especially when applied early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of diabetic foot wounds with acellular fish skin graft rich in omega-3: a prospective evaluation. Woodrow, T., Chant, T., Chant, H.[2019]

In a study of 15 pediatric patients using a novel acellular fish skin graft (FSG) derived from cod, rapid wound healing was achieved, with 100% wound area coverage and 95% complete healing, significantly reducing the time to engraftment from an average of 21 days to 12 days when combined with negative pressure wound therapy (NPWT).

The use of FSG resulted in shorter operating times (less than 60 minutes), no reported complications or allergic reactions, and excellent pliability of healed wounds, making it a promising and sustainable option for pediatric skin grafting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of acellular intact fish skin grafts in treating acute paediatric wounds during the COVID-19 pandemic: a case series. Ciprandi, G., Kjartansson, H., Grussu, F., et al.[2022]

Acellular fish skin grafts from Atlantic cod, rich in omega-3 fatty acids like EPA and DHA, have shown increased efficacy in treating chronic, non-healing wounds such as diabetic foot ulcers, leading to faster healing rates compared to standard treatments.

The unique lipid profile of fish skin grafts not only promotes wound closure but also provides barrier protection against bacteria and modulates the inflammatory response, enhancing overall wound healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fish Skin Grafts with Omega-3 for Treatment of Chronic Wounds: Exploring the Role of Omega-3 Fatty Acids in Wound Healing and A Review of Clinical Healing Outcomes. Seth, N., Chopra, D., Lev-Tov, H.[2022]

In a study of 51 patients with diabetic foot ulcers, the use of acellular fish skin grafts resulted in an impressive 87.57% reduction in wound surface area over 16 weeks, with 60.34% of wounds fully healed.

The findings support previous research indicating that acellular fish skin grafts can effectively promote wound healing by facilitating the transition from chronic to acute healing stages, particularly showing rapid improvement in the first 4 weeks after application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acellular Fish Skin Graft Use for Diabetic Lower Extremity Wound Healing: A Retrospective Study of 58 Ulcerations and a Literature Review. Michael, S., Winters, C., Khan, M.[2020]

In a study of 51 patients with hard-to-heal venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs), the use of intact fish skin grafts (FSGs) led to faster healing than predicted by standard care (SOC), with some wounds healing over 50% sooner.

FSGs were particularly effective for wounds that were unlikely to heal with SOC, demonstrating the potential to change the healing trajectory even for wounds that initially increased in size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faster Than Projected Healing in Chronic Venous and Diabetic Foot Ulcers When Treated with Intact Fish Skin Grafts Compared to Expected Healing Times for Standard of Care: An Outcome-Based Model from a Swiss Hospital. Zehnder, T., Blatti, M.[2022]

The Kerecis™ Omega3 Wound matrix, derived from fish skin, was used to treat 25 complicated wounds in 23 patients, showing effectiveness in promoting healing where conventional treatments had failed.

Patients experienced a reduction in analgesic intake after starting treatment with the Omega3 Wound matrix, suggesting potential pain-relieving benefits alongside its wound healing properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The marine Omega3 wound matrix for treatment of complicated wounds: A multicenter experience report. Dorweiler, B., Trinh, TT., Dünschede, F., et al.[2022]

Intact fish skin grafts (iFSGs) showed promising results in promoting wound granulation and providing pain relief in two patients with extensive leg ulcers following necrotizing fasciitis, with no complications or allergic reactions reported.

The application of iFSGs was easy and led to excellent functional and cosmetic outcomes after subsequent autologous skin grafting, suggesting their potential as a valuable treatment option for necrotizing fasciitis and possibly other wound types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Intact Fish Skin Grafts in the Treatment of Necrotizing Fasciitis of the Leg: Early Clinical Experience and Literature Review on Indications for Intact Fish Skin Grafts. Dueppers, P., Bozalka, R., Kopp, R., et al.[2023]

In a study involving 94 patients with diabetic foot ulcers, the use of acellular fish skin grafts resulted in a significantly higher healing rate of 63.0% compared to 31.3% for the standard collagen alginate dressing after 12 weeks (P = 0.0036).

Both treatment groups had a similar mean healing time of 7 weeks, but the fish skin graft required a median of 6 applications to achieve healing, indicating its potential as an effective alternative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the effect of omega-3-rich fish skin in the treatment of chronic, nonresponsive diabetic foot ulcers: penultimate analysis of a multicenter, prospective, randomized controlled trial. Lullove, EJ., Liden, B., McEneaney, P., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10532083/

The Use of Intact Fish Skin Grafts in the Treatment ...

Faster wound healing rates and better functional and cosmetic outcomes were observed due to their additionally postulated anti-inflammatory and ...

2.

kerecis.com

kerecis.com/fish-skin-for-wound-healing/

Fish Skin for Wound Healing

Ideal for the management of venous leg ulcers in outpatient care settings; Pre-meshed intact fish skin graft, ratio 2:1; Expands to cover wounds of 100 cm ...

3.

kerecis.com

kerecis.com/publications/

Scientific Publications

Intact Fish Skin Graft to Treat Deep Diabetic Foot Ulcers. Dured Dardari, M.D, Ph.D., Alberto Piaggesi, M.D., Louis Potier, M.D., Ariane Sultan, M.D., Holger ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9786154/

Intact Fish Skin Graft vs. Standard of Care in Patients with ...

The study has parallel treatment groups: Group 1 treatment with Kerecis® Omega3 Wound™ versus Group 2 treatment with standard of care. The ...

5.

researchgate.net

researchgate.net/publication/365939310_Intact_Fish_Skin_Graft_vs_Standard_of_Care_in_Patients_with_Neuroischaemic_Diabetic_Foot_Ulcers_KereFish_Study_An_International_Multicentre_Double-Blind_Randomised_Controlled_Trial_Study_Design_and_Ra

(PDF) Intact Fish Skin Graft vs. Standard of Care in Patients ...

Studies on its use as a skin substitute in nonhealing ulcers ... Here, we describe the outcomes of using FSG (Kerecis Omega3 Wound; Kerecis ...

6.

mdpi.com

mdpi.com/2077-0383/12/18/6001

The Use of Intact Fish Skin Grafts in the Treatment ...

Faster wound healing rates and better functional and cosmetic outcomes were observed due to their additionally postulated anti-inflammatory and ...

7.

kerecis.com

kerecis.com/graftguide/

GraftGuide

GraftGuide is intact fish skin which is used to regenerate tissue on surgical, traumatic, and acute wounds. Because there is no known risk of viral or prion ...