Venous Leg Ulcer
Conditions
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: 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
Interventions
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.
DEVICENormal Saline and Placebo Gel
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.
Sponsors
B. Braun Ltd. Centre of Excellence Infection Control
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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%)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change of Wound Size From Baseline to Last Visit | 12 Weeks | — |
| Healing of Target Ulcer atV6/EOS | 12 weeks | Number of ulcers healed at V6/EOS |
| Absolute Change of Target Ulcer From Baseline to Last Visit | 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Different Microganisms at V6/EoS | 12 Weeks | — |
| Pain | 12 Weeks | 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'. |
| Condition of Wound Bed | 12 Weeks | Sum of granulation and epithelium (% of wound bed), absolute change from baseline to V6/EoS |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prontosan Wound Solution and Gel Polihexanide (0.1%), Betaine (0,1%), Purifed water | 17 |
| Normal Saline and Placebo Gel Sodium Choride 0.9% Solution, Neutral Gel without Polihexanide, without Betaine | 17 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Therapeutic failure | 3 | 3 |
Baseline characteristics
| Characteristic | Prontosan Wound Solution and Gel | Normal Saline and Placebo Gel | Total |
|---|---|---|---|
| Age, Continuous | 71.1 years STANDARD_DEVIATION 9.6 | 73.1 years STANDARD_DEVIATION 10.7 | 71.6 years STANDARD_DEVIATION 10.1 |
| Duration of leg ulceration | 36 months | 84 months | 54 months |
| Region of Enrollment United Kingdom | 17 participants | 17 participants | 34 participants |
| Sex: Female, Male Female | 12 Participants | 7 Participants | 19 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 17 | 15 / 17 |
| serious Total, serious adverse events | 0 / 17 | 1 / 17 |
Outcome results
Primary
Absolute Change of Target Ulcer From Baseline to Last Visit
Time frame: 12 weeks
Population: per protocol analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prontosan Wound Irrigation Solution and Gel | Absolute Change of Target Ulcer From Baseline to Last Visit | -3.00 square centimeters | Standard Error 1.45 |
| Normal Saline and Inactive Gel | Absolute Change of Target Ulcer From Baseline to Last Visit | -3.01 square centimeters | Standard Error 1.54 |
p-value: 0.9945F-test
Primary
Healing of Target Ulcer atV6/EOS
Number of ulcers healed at V6/EOS
Time frame: 12 weeks
Population: per protocol analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prontosan Wound Irrigation Solution and Gel | Healing of Target Ulcer atV6/EOS | 8 ulcers |
| Normal Saline and Inactive Gel | Healing of Target Ulcer atV6/EOS | 5 ulcers |
p-value: 0.4905Fisher Exact
Primary
Percent Change of Wound Size From Baseline to Last Visit
Time frame: 12 Weeks
Population: Per protocol set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prontosan Wound Irrigation Solution and Gel | Percent Change of Wound Size From Baseline to Last Visit | -64.98 percentage change in wound size (cm2) | Standard Error 12.32 |
| Normal Saline and Inactive Gel | Percent Change of Wound Size From Baseline to Last Visit | -42.78 percentage change in wound size (cm2) | Standard Error 13.13 |
p-value: 0.2317F-test
Secondary
Condition of Wound Bed
Sum of granulation and epithelium (% of wound bed), absolute change from baseline to V6/EoS
Time frame: 12 Weeks
Population: per protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prontosan Wound Irrigation Solution and Gel | Condition of Wound Bed | 7.1 percentage of of wound bed | Standard Deviation 38.9 |
| Normal Saline and Inactive Gel | Condition of Wound Bed | -1.5 percentage of of wound bed | Standard Deviation 52 |
Secondary
Number of Different Microganisms at V6/EoS
Time frame: 12 Weeks
Population: per protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prontosan Wound Irrigation Solution and Gel | Number of Different Microganisms at V6/EoS | 0.8 Number of microgasism species | Standard Deviation 0.9 |
| Normal Saline and Inactive Gel | Number of Different Microganisms at V6/EoS | 1.0 Number of microgasism species | Standard Deviation 0.8 |
Secondary
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'.
Time frame: 12 Weeks
Population: per protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prontosan Wound Irrigation Solution and Gel | Pain | -8.9 mm | Standard Deviation 20.4 |
| Normal Saline and Inactive Gel | Pain | -12.8 mm | Standard Deviation 26 |