The primary objective of the study is to evaluate the efficacy of Prontosan® Wound Irrigation Solution and Prontosan® Wound Gel in the treatment of hard-to heal venous leg ulcers compared to control saline irrigation solution and inactive gel by showing a reduction in size over a 12 week period.

SUMMARY

Sponsor: B. BRAUN Medical AG

Trade name: Prontosan® Wound Irrigation Solution Prontosan® Wound Gel

Active substance: Polihexanide (0.1%) Betaine (0.1%)

Study Duration (per patient):

13 weeks, including the 1 week run in period

Primary Objective:

To evaluate the efficacy of the combination of Prontosan® Wound Irrigation Solution and Prontosan® Wound Gel in the reduction of wound size of hard-to-heal venous leg ulcers compared to control saline irrigation solution and inactive gel.

Secondary Objectives:

To assess the change in bio-burden (assessment of organisms present) and to determine local tolerance as well as reduction in pain and to monitor exudate control.

Methodology:

A pilot randomised, double-blind, controlled clinical trial at a single centre

Planned number of patients:

A sample size of N= 15 evaluable patients was estimated for each treatment group (group "A" and "B"). Adding a dropout rate of approx. 25% results in a total number of patients for both treatment groups of N=38.

Study Visits:

Visit 0 (-1 week) - Screening Visit 1 ( Week 0) - Treatment and assessment visit Visit 2 (Week 1, day 7 +/- 1 day) - Treatment and assessment visit Visit 3 (Week 2, day14 +/- 1 day) - Treatment and assessment visit Visit 4 (Week 4, day 28 +/- 2 days) - Treatment and assessment visit Visit 5 (Week 8, day 56 +/- 2 days) - Treatment and assessment visit Visit 6 (Week 12, day 84 +/- 2 days) - End of study following 12 weeks of treatment or at healing whichever is soonest

The number of additional visits will be recorded in the Case Report Forms.

Treatment efficacy assessment:

Clinical signs and symptoms will be compared between the two randomised groups with microbiological analysis and, computer planimetry assessments of ulcer size, using Visitrak™ (Smith & Nephew), and digital photography at entry to the study, at each planned study visit and at healing or 12 weeks, whichever is soonest.

Tolerance assessment:

The tolerability of study treatment will be evaluation based on the intensity and the course of adverse events (undesired concomitant effects, both subjectively perceived symptoms and objectively detected signs of disease). Tolerance assessments will take place from visit 2 onwards

Assessment methods:

1. Assessment of clinical signs and symptoms, in particular related to development of infection:

   • reduction of slough and necrotic tissue
   • control of exudate
   • presence of granulation tissue
   • reduction of inflammatory signs (surrounding skin)
   • pain

2. Ulcer computerised planimetry using Visitrak™

3. Microbiological analysis for bioburden (the bioburden within an ulcer relates to a microbiological qualitative and quantitative assessment of organisms present) assessed by wound swab or biopsy

4. Serial photography with blinded assessment of progress using linear analogue scale

Inclusion Criteria:

• Males and females aged > 18 who are able to give informed consent
• Patients with a chronic venous leg ulcer at any location below the knee joint (CVI grade C6 according to CEAP classification = trophic lesions and open ulcer)
• Venous leg ulcer present for ≥4 weeks
• Surface area of the target ulcer ≥2cm2 and <100cm2 with the largest length not being >10cm
• ABPI ≥ 0.7

Exclusion Criteria:

• Age below 18 years
• Females of child bearing potential who are not willing to use a method of highly effective contraception during the entire study
• Pregnant or breast feeding women
• Signs and symptoms of clinical infection, or current use of antiseptics or antibiotics
• Involvement in other trials within the past 1 month
• Sensitivity to any of the components of Prontosan® or dressing material
• Intolerance to compression therapy
• Active osteomyelitis in the ulceration area
• Active rheumatoid or collagen disease of blood vessels treated with corticosteroids
• Chronic diseases that could impact the course of the study (malicious cancer, TB, AIDS, mental illnesses)
• Plasma protein below 4 g/dl
• Anaemia: haemoglobin below 10 g/dl
• Poorly controlled Diabetes (HBA1C > 12%)

Most likely the non-statistical significant results are due to the small sample size. No sample size calculation and statistical analysis was planned a priori because it was a pilot study.