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Safety and Efficacy of EscharEx (concentrate of proteolytic enzymes enriched in bromelain) in Adults with Venous Leg Ulcers

InvestigationalNo placebo

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What is this trial about?

A plain-language summary of the goals, design and what participants do

The condition studied is Venous Leg Ulcer, a chronic wound on the lower leg caused by poor blood flow in the veins. The investigational product is a topical gel that contains a concentrate of proteolytic enzymes enriched in bromelain and is called EscharEx. A matching placebo gel without the active enzymes and the usual non-surgical standard of care are also used for comparison.

The purpose of the study is to evaluate the safety and whether EscharEx helps the ulcer heal faster than the placebo gel and the standard care. Safety will be checked by monitoring side effects and vital signs, while effectiveness will be measured by time to complete wound closure, reduction in wound size, pain levels using the Numeric Pain Rating Scale, and the appearance of healthy new tissue.

Participants will receive the assigned treatment applied to the ulcer during a series of weekly visits. At each visit the wound will be examined for pain, size, and signs of cleaning away dead tissue (debridement) and the growth of new healthy tissue (granulation tissue). The study continues until the ulcer is fully closed or the planned follow‑up period ends.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Randomization and assignment
After you agree to take part, you will be placed into one of three groups: the EscharEx group, the placebo gel vehicle group, or the non‑surgical standard of care group. the assignment is decided by a computer program, so you will not know which group you are in.
Step 2
Baseline assessment
Before any treatment starts, study staff will measure the size of your leg ulcer, record your pain level using a numeric scale, check your vital signs (such as blood pressure and heart rate), and take blood samples to evaluate basic laboratory values. these measurements create a reference point for later comparison.
Step 3
Daily treatment applications
If you are assigned to the EscharEx group, a powder containing a concentrate of proteolytic enzymes enriched in bromelain will be mixed into a gel and applied directly to the wound. the amount used is 3500 g per square meter of wound surface. the gel is placed on the ulcer once each day.
If you are assigned to the placebo gel vehicle group, a sterile powder containing only inactive ingredients (lactose, potassium phosphates, and guar gum) will be mixed into a gel and applied in the same way as the active product.
If you are assigned to the non‑surgical standard of care group, you will receive the usual wound‑care dressing and cleaning procedures that are normally used for venous leg ulcers.
The daily applications continue for up to eight consecutive days, unless the study staff decides to stop earlier because the wound is completely cleaned (debrided) or there is a safety concern.
Step 4
Monitoring during daily visits
Each day you will be examined for any new or worsening side effects, both at the wound site and throughout the body.
Your vital signs and blood test results will be checked daily to identify any significant changes.
Pain will be recorded each day using the Numeric Pain Rating Scale.
Step 5
Weekly follow‑up visits
After the daily application period, you will attend weekly visits for the remainder of the study.
During these visits the size of the ulcer will be measured again, pain will be reassessed, and the staff will determine whether the wound has completely closed.
The weekly visits continue until the end of the trial or until the ulcer is fully healed, whichever occurs first.
Step 6
Final assessment and trial completion
At the end of the study period, a comprehensive evaluation will be performed. this includes a final wound measurement, a review of all pain scores, a summary of any adverse events that occurred, and a final set of laboratory tests.
The data collected will be used to compare the safety and effectiveness of EscharEx, the placebo gel vehicle, and the non‑surgical standard of care.

Who can join the trial?

6 criteria

Men or women who are older than 18 years.
Having a Venous Leg Ulcer (VLU) confirmed by medical history, a physical exam, and an ultrasound scan that shows venous insufficiency (poor blood flow in the leg veins).
The wound must have been present for at least 4 weeks but no longer than 18 months.
At least 50% of the wound area must be covered by dead or thick tissue (called necrotic, slough, or fibrin tissue) after the wound is cleaned with wet gauze and sterile saline or water and mild soap.
The size of the wound must be between 2 and 40 cm² (square centimeters), measured with a device called eKare inSightTM.
The participant must understand what the study involves, be able to follow the study schedule, and sign a written informed consent form before any procedures.

Who cannot join the trial?

37 criteria

If the ulcer gets noticeably smaller (more than 20% shrinkage) during the 7‑day screening period, you cannot join the study.
If you have another leg ulcer that is at least 2 cm² in size and located 2‑5 cm away from the wound being studied, you are not eligible.
If there are signs of infection around the wound, such as pus, an abscess, cellulitis or erysipelas, you cannot participate.
If the skin around the wound is severely damaged (for example, an abrasion, erosion or peeling that extends more than 2 cm from the wound edge), you are excluded.
If you have gangrene, a serious whole‑body infection (sepsis), or a bone infection called osteomyelitis, you cannot be enrolled.
If a doctor suspects skin cancer (such as basal cell carcinoma, squamous cell carcinoma, melanoma or sarcoma) near the wound and it has not been ruled out by a tissue sample (biopsy), you are not eligible.
If you have chronic skin problems unrelated to the ulcer that are located next to the wound, you cannot take part.
If you have chronic skin conditions (for example, chronic itching, psoriasis, panniculitis or pyoderma gangrenosum) that could get worse from local trauma or cleaning of the wound, you are excluded.
If the wound has hidden tunnels or channels (called sinus tracts) that go under healthy tissue or reach bone, fascia or the periosteum, you cannot join.
If you have primary lymphatic swelling of the leg, known as lymphedema, you are not eligible.
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If blood flow to your leg is significantly reduced, as shown by any of the following tests:
- Toe‑Brachial Index (TBI) ≤ 0.50
- Ankle‑Brachial Index (ABI) ≤ 0.70
- Skin Perfusion Pressure (SPP) ≤ 40 mmHg
- Transcutaneous oximetry (TCOM) ≤ 40 mmHg
- Absence of normal (bi‑phasic or tri‑phasic) Doppler waveforms
- If a wound you had before the study is covered by a thick, dead‑tissue layer (eschar) that is heavily saturated with iodine, or by a pseudo‑eschar created by silver sulfadiazine (SSD) treatment, you are excluded.
- If you have a known allergy or sensitivity to pineapples, bromelain, papaya, papain, latex (including the “latex‑fruit syndrome”), bee venom, or olive tree pollen, you cannot join.
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  If you have poor overall health or nutrition, such as:
  - Low albumin (< 2.5 g/dL)
  - Uncontrolled diabetes (HbA1c > 12 %)
  - Anemia (hemoglobin < 8 g/dL)
  - Very low or very high white‑blood‑cell counts ( < 3,000/µL or > 15,000/µL)
  - Low neutrophils ( ≤ 1,000/µL)
  - Low platelets ( < 100,000/µL)
  - Abnormal liver enzymes (AST or ALT > 2 × upper normal limit)
  - Severe kidney problems (creatinine > 2.5 mg/dL or eGFR < 30 mL/min/1.73 m²)
  - Very high body‑mass index (BMI > 48)
  - If your blood clotting tests show an INR > 2 or a PTT more than twice the normal limit, unless you are on stable warfarin therapy with controlled levels, you cannot participate.
  - If you are receiving regular kidney treatment such as hemodialysis or peritoneal dialysis, you are excluded.
  - If you have any serious condition that could make the study unsafe—for example, unstable heart disease, lung disease, liver disease, blood disorders, immune problems, active cancer, or any condition that threatens your life—you cannot join.
  - If you have a recent or current acute injury or illness that the investigator believes could compromise your safety, you are not eligible.
  - If you are currently taking, have taken in the past three months, or plan to take during the study any medication that is known to slow wound healing, such as systemic steroids > 10 mg prednisone (or equivalent) for more than two weeks, immunosuppressive drugs, chemotherapy, or radiation therapy, you are excluded (low, intermittent doses may be allowed at the investigator’s discretion).
  - If you used the medication Pentoxifylline within two weeks before screening, you cannot participate.
  - If you had a venous ablation procedure (a treatment to close faulty veins) within one month before enrollment near the wound, you are excluded.
  - If you are unable to give legal consent because of mental incapacity (for example, dementia or severe psychiatric illness), you cannot join.
  - If you are using non‑approved drugs or have a problem with alcohol abuse, you are not eligible.
  - If you are pregnant (positive pregnancy test) or are breastfeeding, you cannot participate.
  - If you have been exposed to the study drug or a similar investigational product within one month before enrollment, or if you plan to join another clinical trial while in this study, you are excluded.

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Investigated drugs

EscharEx
is a topical powder that turns into a gel when applied to a wound. It contains a concentrate of natural enzymes, mainly bromelain, which help break down dead tissue (eschar) on the surface of the ulcer. By softening and removing this dead tissue, the product aims to create a cleaner wound bed, making it easier for the body’s own healing processes to work and for new skin to grow.
Non‑surgical standard of care (NSSOC)
refers to the usual treatments used for venous leg ulcers that do not involve surgery. This typically includes cleaning the wound, applying appropriate dressings, and using compression therapy to improve blood flow in the leg. These measures are intended to protect the ulcer, keep it moist, and support natural healing.

What is already known about the treatment

EscharEx - It is applied as a powder that forms a gel and is placed directly on the wound surface. The product contains a concentrate of proteolytic enzymes enriched with bromelain, which is already used in some topical wound‑care preparations but is not yet widely approved as a prescription drug. It is intended to help heal venous leg ulcers by gently breaking down dead tissue and reducing inflammation. The enzymes work by cutting protein fibers in the wound scab, allowing new healthy tissue to grow, and it belongs to the class of proteolytic enzyme topical agents.

Investigated diseases

Venous Leg Ulcer - A Venous Leg Ulcer is a chronic wound that develops on the lower leg, usually near the ankle, due to poor blood flow in the veins. It begins as a small area of skin breakdown that can slowly enlarge if the underlying circulation problem persists. Over time the ulcer may develop a moist surface with new tissue growth, but it often remains open for weeks or months. The wound can become larger or deeper if pressure, infection, or continued venous insufficiency is not addressed.