A Multicentre European Study to Evaluate Granulox® Used in the Treatment Pathway of Predominantly Chronic Venous Leg Ulcers (VLUs).

Multicentre, Prospective, Randomized, Open-label, Assessor Blinded Study to Evaluate Granulox® Used as Adjunct Therapy to Defined Standard of Care vs. Defined Standard of Care for the Treatment of Predominantly Chronic Venous Leg Ulcers (VLUs)

The investigation is designed as an open label, randomized, prospective, assessor blinded, multi centre investigation.

254 evaluable subjects will be randomized to either standard of care group or standard of care with Granulox added as an adjunct therapy in predominantly venous leg ulcer subjects. Standard of care wound management will be completed, including wound cleansing, debridement if necessary and application of a suitable dressing and compression system until complete wound closure.

The study will be divided into two phases. Firstly, a two week run-in period to ensure compliance to compression therapy followed by a 20 weeks treatment period starting with randomization and allocation of treatment.

The current study is designed to verify previous clinical findings and to pinpoint clinically relevant efficacy, associated to intended use of Granulox® as a therapy added to a defined standard of care in the management of chronic VLUs. The most relevant outcome is considered to be an increase in healing of chronic VLUs over a period of 20 weeks.

This is a multi-centre European open label randomised 2-arm parallel group study. The study will include multiple European counties (e.g. France, Germany, UK, Poland, Croatia and Czech Republic), with approximately 2-7 clinics per country.

The study will run with a two-phase set-up, with a 14 days run-in period and a an up to 20 weeks treatment period starting with randomization and allocation of treatment. Confirmation of wound closure is further assessed after a 15 day followup period.

The primary objective of the study is to compare wound healing between management of chronic VLUs with or without added Granulox®. The main efficacy criterion is Confirmed Complete wound Closure (CCC).

Inclusion Criteria:

1. Signed consent to participate.
2. No planned hospitalization in the forthcoming 20 weeks.
3. Male or female (women of childbearing age must have an acceptable method of birth control).
4. Age >18 years.
5. Recent (less than 12 months) doppler or duplex colour ultrasonography compatible with chronic venous insufficiency.
6. ABPI (less than 3 months) ≥0.7 for both legs. If ABPI >1.4, then big toe pressure >60mmHg is required or an alternative measurement verifying normal distal arterial flow.
7. At least one or more supra- or peri-malleolar leg ulcers and no foot ulcer or another chronic wound.
8. In case of two or more ulcers, select ulcer with the highest PUSH score at randomization and treat the non-selected ulcer in the same way as ulcers in the control group (standard of care).
9. In case of two or more ulcers on the same limb, ensure that the distance between each ulcer is 3 cm as measured from the margins of each ulcer that are closest to one another.
10. Wound duration ≥ 8 weeks and ≤60 months.
11. At randomization, the ulcer area should be 3 cm2 - 70 cm² and should not have decreased by more than 30% during the 2-week run-in period.
12. Less than 50% of the wound area should be covered with fibrinous tissue at randomization and after debridement.
13. Patients considered as compliant/adherent to the compression device during the run-in period (i.e. no more than 2 days without compression over the 2-week run-in period).
14. No clinically significant comorbidities requiring the use of systemic steroids or any cytotoxic or immunosuppressive agents.

Exclusion Criteria:

1. Infected ulcer according to the judgment of the investigator defined as any wound condition requiring the prescription or continuation of systemic antibiotic therapy at randomization.
2. Circumferential wounds.
3. Wound covered fully or partially by necrotic tissue (black tissue).
4. Patients who will have problems following the protocol, especially compression therapy.
5. Patients included in another on-going clinical investigation, or patients who have participated in a clinical investigation during the past 30 days.
6. Wounds treated with dressings containing an active component (e.g. silver, nanooligosaccharide factor (NOSF), charcoal, chlorhexidine, iodine or ibuprofen) 14 days prior to study enrollment.
7. Patient with a systemic infection not controlled by suitable antibiotic treatment.
8. Current treatment with radiotherapy, chemotherapy, immunosuppressant drugs or high doses of oral corticosteroids (>10 mg Predinsolone or equivalent) if any.
9. Patient with deep vein thrombosis within 3 months prior to inclusion.
10. Known allergy/hypersensitivity to the ingredients of the dressings and/or Granulox®.
11. Malignant wounds.
12. Endovenous surgery planned or performed within the past 30 days.
13. Primary lymphoedema caused by congenital/developmental defect, i.e. Milroy's disease (congenital lymphedema), Meige's disease (lymphedema praecox), or Late-onset lymphedema (lymphedema tarda).