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

Venous Leg Ulcer Clinical Trial

— Granulox01  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04181320
• Other study ID #: Granulox01 (PD-568268)
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 8, 2020
• Est. completion date: December 30, 2023

Study information

• Verified date: January 2023
• Source: Molnlycke Health Care AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Secondary objectives include comparisons of management of chronic VLUs with or without added Granulox® with regards to:

• Wound healing by means of Possible Complete wound Closure (PCC), Wound Area Regression (WAR), time to healing, trajectories, pressure ulcer scale for healing (PUSH) score, and clinical assessment.

• Patient Reported Outcomes (PRO) for health-related quality of life (HRQoL)/quality of life (QoL), pain and pain intensity, and impression of change.

• Acceptability of and compliance to therapy.

• Cost-effectiveness.

• Safety by means of Adverse Events (AE) and Serious Adverse Events (SAE) reporting.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 110
• Est. completion date: December 30, 2023
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Leg Ulcer
• Ulcer
• Varicose Ulcer
• Venous Leg Ulcer

Intervention

Device:
• Venous Leg Ulcer Standard of Care with Granulox
Granulox will be added as an adjunct therapy to defined standard of care in subjects with predominantly venous leg ulcers.

Locations

Country	Name	City	State
Croatia	Klinicki odjel za vaskularnu kirurgiju	Split
Croatia	University Hospital Dubrava	Zagreb
Croatia	Zavod za vaskularnu kirurgiju	Zagreb
Czechia	CHIR-Chirurgické oddeleni	Jihlava
Czechia	U Nemocnice v Praze	Prague
Czechia	Salvatella s.r.o.	Trinec	Dolni Lomna
France	Hopital Nord Franche-Comte	Belfort	Trevenans
France	Hopital Michallon	Grenoble	La Tronche
France	Hopital Rothschild - AP-HP	Paris	Île-de-France
Germany	Gemeinschaftspraxis Drees.K.CH.Busch/v.d.Ecken	Dortmund
Germany	Technische Universitaet Dresden - Universitaetsklinikum Carl Gustav Carus - Klinik fuer Dermatologie	Dresden
Germany	University Hospital Erlangen	Erlangen
Germany	Department od Dermatology, Venerology and Allergology, University of Essen	Essen	North Rhine-Westphalia
Germany	Oberhausen Sterkrade (Zweigpraxis)	Oberhausen
Hungary	Clinexpert Kft	Budapest
Hungary	Debreceni Egyetem, Klinikai Kozpont, Borgyogyaszati Klinika	Debrecen
Hungary	Markhot Ferenc oktatókórház és rendelöintézet	Eger
Hungary	Bugat Pal Korhaz	Gyöngyös	Heves
Hungary	BKS Research Kft	Hatvan
Hungary	DermaMed Research Kft	Orosháza	Oroshaza
Poland	Szpital Uniwersytecki nr 1 im. dr. A. Jurasza w Bydgoszczy Poradnia Leczenia Ran Przewleklych	Bydgoszcz
Poland	Uslugi Medyczne PRO-MED Sp. z.o.o	Gliwice	Gliwicie
Poland	Nzoz Gam-Med	Kielce
Poland	MIKOMED Sp. Z.o.o.	Lódz
Poland	Braci Wieniawskick 12B	Lublin
United Kingdom	Hull University Teaching Hospitals NHS Trust	Hull
United Kingdom	Accelerate CIC	London

Sponsors (1)

Lead Sponsor	Collaborator
Molnlycke Health Care AB

Countries where clinical trial is conducted

Croatia,  Czechia,  France,  Germany,  Hungary,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of complete confirmed wound closure (CCC) will be measured and compared for 254 subjects divided into standard of care versus standard of care with Granulox.	Derived by two blinded quantifications of 100% re-epithelialization by PictZar, 15 days (+/- 3 days) apart.	20 weeks
Secondary	Healing time	Calculated from time in days from baseline to the first observation of CCC.	20 weeks
Secondary	Wound status	Wound size measured, i.e. width, length, circumference or perimeter, via PictZar®.; Exudate amount and nature.; Tissue (i.e. fibrinous, granulation, epithelisation) type, i.e. area and percentage from total wound.; Skin condition, i.e. peri-wound, redness/irritation/eczema, maceration, blistering, stripping, trauma.; Local infection status, i.e. pain, perilesional skin erythema, oedema, malodour, levels of exudate.; Cleansing specification.; Debridement specification.	20 weeks
Secondary	Wound Area Regression (WAR)	Calculated variables 90WAR (i.e. 90% WAR from baseline, based on wound photos) and 50WAR (i.e. 50% WAR from baseline, based on wound photos).	20 weeks
Secondary	Rate of possible confirmed wound closure (PCC) will be measured and compared for 254 subjects divided into standard of care versus standard of care with Granulox.	derived from one measurements of 100% reepithelialization by via PictZar®.	20 weeks
Secondary	Healing trajectories	Calculated progression of the re-epithelialization wave over time.	20 weeks
Secondary	Pressure Ulcer Scale for Healing tool	Wound changes over time will be captured by the Pressure Ulcer Scale for Healing tool. Total score from 0 to 17 where the lower the score the better the outcome e.g when the wound has closed, score as '0'	20 weeks
Secondary	Blind assessment of wound healing	Assessor-blinded clinical verification of CCC and PCC based on patient-series of wound photos assessed by independent and experienced clinicians, unaware of treatment allocation.	20 weeks
Secondary	Health related Quality of Life assessment by EQ-5D-5L	Patient report outcome questionnaire to evaluate health and quality of life. The higher the score the better the outcome e.g 100 means the best health.	20 weeks
Secondary	Wound specific Quality of Life assessment by Wound-QoL	Patient report outcome questionnaire to evaluate wound specific quality of life. A 5 point scale based on 17 questions of the wound in the last seven days from 'not at all' to 'very much'. The lower the score at 'not at all' the better the outcome e.g my wound hurt (not at all).	20 weeks
Secondary	Numerical Rating Scale (NRS)	Patient report outcome questionnaire to evaluate pain. A total score range of 0 - 10. The lower the score the better the outcome e.g 0 is no pain.	20 weeks
Secondary	Acceptability of care	Assessment of acceptability of care by means of a 5-item scale (e.g. very poor, poor, average, good, very good) where very good is a better outcome. This will be performed at the final visit only.	20 weeks
Secondary	Ease of care	Assessment of ease of care by means of a 5-item scale (e.g. very poor, poor, average, good, very good) where very good is a better outcome. This will be performed at the final visit only.	20 weeks
Secondary	Evaluation of patient compliant to venous compression	Evaluation will be based on a 3 point scale from fully compliance, moderately compliance or no compliance to compression therapy where fully compliance is a better outcome. Compliance to compression therapy will be defined as the following: Fully compliance (defined as 7/7 days) = continue in study; Moderately compromised compliance (defined as 2 or 3 days maximum without compression) = continue in study; No compliance (defined as >3 without compression) = discontinue from study	20 weeks
Secondary	Cost Effectiveness	Collection of cost parameters such as micro costing and resource utilization will be made in the study. These include: Wound care consumables associated with dressings (captured both at site by investigator and in the patient specific diary by the study nurse); Frequency of dressings changes (captured both at site by investigator and in the patient specific diary by the study nurse). In addition, reporting of adverse events (i.e. infection and hospitalization) will be used as a basis for economic information together with country-specific costs.	20 weeks