Trial on the Efficacy of Prontosan Wound Irrigation Solution and Prontosan Wound Gel

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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: 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 Ulcer computerised planimetry using Visitrak™ 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 Serial photography with blinded assessment of progress using linear analogue scale

Official Title
-----------------
Pilot, Randomised, Double-blind, Controlled Clinical Trial on the Combined Efficacy of Prontosan Wound Irrigation Solution and Prontosan Wound Gel in the Reduction in Size and Change in Bioburden of Hard-to-heal Venous Leg Ulcers

Conditions
-----------------
Venous Leg Ulcer

Intervention / Treatment
-----------------
* Device: Prontosan Wound Irrigation Solution and Prontosan Wound Gel
* Device: Normal Saline and Placebo Gel


Participation Criteria
=================
Eligibility Criteria
-----------------
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%)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prontosan Wound Solution and Gel<br>Cleansing the wound bed, a sterile gauze dressing impregnated with the Prontosan® or saline solution, removed after 15 minutes; wound will be sparingly covered with Prontosan® Wound Gel or inactive gel. Secondary dressing to be a semi occlusive dressing. Secure the dressing to the wound with tubifast and short stretch compression system Dressings will be changed and the treatment procedure will be repeated every 3 days (+/- 1 day) | Device: Prontosan Wound Irrigation Solution and Prontosan Wound Gel<br>* The treatment procedures (after a 1 week run-in) include: Cleansing the wound bed, at dressing change, with Prontosan® Wound Irrigation Solution or saline solution; a sterile gauze dressing impregnated with the Prontosan® or saline solution, depending on randomisation, will be placed on the wound in the form of a moist compress and removed after 15 minutes; the wound will be sparingly covered with Prontosan® Wound Gel or inactive gel, depending on randomisation Secondary dressing to be a semi occlusive dressing Secure the dressing to the wound with tubifast and short stretch compression system Dressings will be changed and the treatment procedure will be repeated every 3 days (+/- 1 day) when clinical, microbiological, planimetry and photographic assessments will be made. The randomised solution will also be used for removal of the dressing from the wound at the start of dressing change.<br>|
| Placebo Comparator: Normal Saline and Placebo Gel<br>Cleansing the wound bed, a sterile gauze dressing impregnated with the Prontosan® or saline solution, removed after 15 minutes; wound will be sparingly covered with Prontosan® Wound Gel or inactive gel. Secondary dressing to be a semi occlusive dressing. Secure the dressing to the wound with tubifast and short stretch compression system Dressings will be changed and the treatment procedure will be repeated every 3 days (+/- 1 day) | Device: Normal Saline and Placebo Gel<br>* The treatment procedures (after a 1 week run-in) include: Cleansing the wound bed, at dressing change, with Prontosan® Wound Irrigation Solution or saline solution; a sterile gauze dressing impregnated with the Prontosan® or saline solution, depending on randomisation, will be placed on the wound in the form of a moist compress and removed after 15 minutes; the wound will be sparingly covered with Prontosan® Wound Gel or inactive gel, depending on randomisation Secondary dressing to be a semi occlusive dressing Secure the dressing to the wound with tubifast and short stretch compression system Dressings will be changed and the treatment procedure will be repeated every 3 days (+/- 1 day) when clinical, microbiological, planimetry and photographic assessments will be made. The randomised solution will also be used for removal of the dressing from the wound at the start of dressing change.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change of Wound Size From Baseline to Last Visit |  | 12 Weeks | 
| Healing of Target Ulcer atV6/EOS | Number of ulcers healed at V6/EOS | 12 weeks | 
| Absolute Change of Target Ulcer From Baseline to Last Visit |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Different Microganisms at V6/EoS |  | 12 Weeks | 
| Pain | Absolute change (mm VAS) from baseline to V6/EoS. Pain intensity assessed by patient. At each study visit the patients assessed their pain intensity using a 100 mm Visual Analogue Scale (VAS). Thereby 0 mm represented 'no pain' and 100 mm 'worst possible pain'. | 12 Weeks | 
| Condition of Wound Bed | Sum of granulation and epithelium (% of wound bed), absolute change from baseline to V6/EoS | 12 Weeks |