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

• Sponsor: B. Braun Ltd. Centre of Excellence Infection Control (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01153633
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Arms: 2
• Duration (Months): 24
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Venous Leg Ulcer	Device: Prontosan Wound Irrigation Solution and Prontosan Wound Gel; Device: Normal Saline and Placebo Gel	Phase 4

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

1. Ulcer computerised planimetry using Visitrak™

2. 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

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Prontosan Wound Solution and Gel 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; 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.
Placebo Comparator: Normal Saline and Placebo Gel 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; 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.

Outcome Measures

Primary Outcome Measures

1. Percent Change of Wound Size From Baseline to Last Visit [12 Weeks]

2. Healing of Target Ulcer atV6/EOS [12 weeks]

   Number of ulcers healed at V6/EOS

3. Absolute Change of Target Ulcer From Baseline to Last Visit [12 weeks]

Secondary Outcome Measures

1. Number of Different Microganisms at V6/EoS [12 Weeks]

2. 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'.

3. Condition of Wound Bed [12 Weeks]

   Sum of granulation and epithelium (% of wound bed), absolute change from baseline to V6/EoS

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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%)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiff University, Department of Wound Healing	Cardiff	Wales	United Kingdom	CF14 4XN

Sponsors and Collaborators

• B. Braun Ltd. Centre of Excellence Infection Control

Investigators

• Principal Investigator: Keith Harding, MD, Cardiff University, Department of Wound Healing

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: B. Braun Ltd. Centre of Excellence Infection Control
• ClinicalTrials.gov Identifier: NCT01153633
• Other Study ID Numbers: OPM-G-H 0901
• First Posted: Jun 30, 2010
• Last Update Posted: Apr 1, 2014
• Last Verified: Mar 1, 2014

• Additional relevant MeSH terms: Varicose Ulcer; Leg Ulcer

Study Results

Participant Flow

Arm/Group Title	Prontosan Wound Solution and Gel	Normal Saline and Placebo Gel
Arm/Group Description	Polihexanide (0.1%), Betaine (0,1%), Purifed water	Sodium Chloride 0.9% Solution Inactive Hydrogel, Hydroxyethylcellulose, Glycerol, purified water, exipients
Period Title: Overall Study
STARTED	17	17
COMPLETED	13	13
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Prontosan Wound Solution and Gel	Normal Saline and Placebo Gel	Total
Arm/Group Description	Polihexanide (0.1%), Betaine (0,1%), Purifed water	Sodium Choride 0.9% Solution, Neutral Gel without Polihexanide, without Betaine	Total of all reporting groups
Overall Participants	17	17	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.1 (9.6)	73.1 (10.7)	71.6 (10.1)
Sex: Female, Male (Count of Participants)
Female	12 70.6%	7 41.2%	19 55.9%
Male	5 29.4%	10 58.8%	15 44.1%
Region of Enrollment (participants) [Number]
United Kingdom	17 100%	17 100%	34 100%
Duration of leg ulceration (months) [Median (Full Range) ]
Median (Full Range) [months]	36	84	54

Outcome Measures

1. Primary Outcome

Title	Percent Change of Wound Size From Baseline to Last Visit
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

Per protocol set

Arm/Group Title	Prontosan Wound Irrigation Solution and Gel	Normal Saline and Inactive Gel
Arm/Group Description	Polihexanide 0.1%, Betaine 01.%, purified water, exipients	Sodium Chloride 0.9% Solution Inactive Hydrogel, Hydroxyethylcellulose, Glycerol, purified water, exipients
Measure Participants	17	15
Least Squares Mean (Standard Error) [percentage change in wound size (cm2)]	-64.98 (12.32)	-42.78 (13.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prontosan Wound Irrigation Solution and Gel, Normal Saline and Inactive Gel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2317
	Comments	F-test (2-sided), ANCOVA with baseline target ulcer size as covariate
	Method	F-test
	Comments

2. Secondary Outcome

Title	Number of Different Microganisms at V6/EoS
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

per protocol analysis

Arm/Group Title	Prontosan Wound Solution and Gel	Normal Saline and Placebo Gel
Arm/Group Description	Polihexanide 0.1%, Betaine 0.1%, purified water, exipients	Sodium Chloride 0.9% Solution Inactive Hydrogel, Hydroxyethylcellulose, Glycerol, purified water, exipients
Measure Participants	17	15
Mean (Standard Deviation) [Number of microgasism species]	0.8 (0.9)	1.0 (0.8)

3. Secondary Outcome

Title	Pain
Description	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

Outcome Measure Data

Analysis Population Description

per protocol analysis

Arm/Group Title	Prontosan Wound Solution and Gel	Normal Saline and Placebo Gel
Arm/Group Description	Polihexanide 0.1%, Betaine 0.1%, purified water, exipients	Sodium Chloride 0.9% Solution Inactive Hydrogel, Hydroxyethylcellulose, Glycerol, purified water, exipients
Measure Participants	17	15
Mean (Standard Deviation) [mm]	-8.9 (20.4)	-12.8 (26.0)

4. Secondary Outcome

Title	Condition of Wound Bed
Description	Sum of granulation and epithelium (% of wound bed), absolute change from baseline to V6/EoS
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

per protocol analysis

Arm/Group Title	Prontosan Wound Solution and Gel	Normal Saline and Placebo Gel
Arm/Group Description	Polihexanide 0.1%, Betaine 0.1%, purified water, exipients	Sodium Chloride 0.9% Solution Inactive Hydrogel, Hydroxyethylcellulose, Glycerol, purified water, exipients
Measure Participants	17	15
Mean (Standard Deviation) [percentage of of wound bed]	7.1 (38.9)	-1.5 (52.0)

5. Primary Outcome

Title	Healing of Target Ulcer atV6/EOS
Description	Number of ulcers healed at V6/EOS
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

per protocol analysis

Arm/Group Title	Prontosan Wound Solution and Gel	Normal Saline and Placebo Gel
Arm/Group Description	Polihexanide 0.1%, Betaine 0.1%, purified water, exipients	Sodium Chloride 0.9% Solution Inactive Hydrogel, Hydroxyethylcellulose, Glycerol, purified water, exipients
Measure Participants	17	15
Number [ulcers]	8	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prontosan Wound Irrigation Solution and Gel, Normal Saline and Inactive Gel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4905
	Comments
	Method	Fisher Exact
	Comments

6. Primary Outcome

Title	Absolute Change of Target Ulcer From Baseline to Last Visit
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

per protocol analysis

Arm/Group Title	Prontosan Wound Solution and Gel	Normal Saline and Placebo Gel
Arm/Group Description	Polihexanide 0.1%, Betaine 0.1%, purified water, exipients	Sodium Chloride 0.9% Solution Inactive Hydrogel, Hydroxyethylcellulose, Glycerol, purified water, exipients
Measure Participants	17	15
Least Squares Mean (Standard Error) [square centimeters]	-3.00 (1.45)	-3.01 (1.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prontosan Wound Irrigation Solution and Gel, Normal Saline and Inactive Gel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9945
	Comments	F-test (2-sided), ANCOVA with baseline target ulcer size as covariate
	Method	F-test
	Comments

Adverse Events

Arm/Group Title	Prontosan Wound Solution and Gel		Normal Saline and Placebo Gel
Arm/Group Description	Polihexanide 0.1%, Betaine 0.1%, purified water, exipients		Sodium Chloride 0.9% Solution Inactive Hydrogel, Hydroxyethylcellulose, Glycerol, purified water, exipients
All Cause Mortality
	Prontosan Wound Solution and Gel		Normal Saline and Placebo Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Prontosan Wound Solution and Gel		Normal Saline and Placebo Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		1/17 (5.9%)
General disorders
Chest Pain	0/17 (0%)	0	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Prontosan Wound Solution and Gel		Normal Saline and Placebo Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/17 (88.2%)		15/17 (88.2%)
Gastrointestinal disorders
Food poisoning	1/17 (5.9%)	1	0/17 (0%)	0
Nausea	1/17 (5.9%)	1	0/17 (0%)	0
Infections and infestations
Celulitis	1/17 (5.9%)	1	1/17 (5.9%)	1
Infected skin ulcer	5/17 (29.4%)	7	4/17 (23.5%)	4
Sinusitis	0/17 (0%)	0	1/17 (5.9%)	1
Viral infection	0/17 (0%)	0	1/17 (5.9%)	1
Bronchitis	1/17 (5.9%)	1	0/17 (0%)	0
Metabolism and nutrition disorders
Gout	0/17 (0%)	0	1/17 (5.9%)	1
Vitamin D deficiency	0/17 (0%)	0	1/17 (5.9%)	1
Musculoskeletal and connective tissue disorders
Mobility decreased	0/17 (0%)	0	1/17 (5.9%)	1
Arthralgia	1/17 (5.9%)	1	0/17 (0%)	0
Back pain	1/17 (5.9%)	1	0/17 (0%)	0
Pain in extremity	1/17 (5.9%)	1	0/17 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	0/17 (0%)	0	1/17 (5.9%)	1
Nervous system disorders
Hypoaesthesia	1/17 (5.9%)	1	0/17 (0%)	0
Skin and subcutaneous tissue disorders
Blister	0/17 (0%)	0	1/17 (5.9%)	1
Eczema	5/17 (29.4%)	6	4/17 (23.5%)	5
Erythema	0/17 (0%)	0	1/17 (5.9%)	1
Excessive granulation tissue	1/17 (5.9%)	1	4/17 (23.5%)	4
Skin maceration	1/17 (5.9%)	1	2/17 (11.8%)	2
Skin ulcer	1/17 (5.9%)	2	3/17 (17.6%)	6
Stasis dermatitis	7/17 (41.2%)	11	6/17 (35.3%)	6
Venous ulcer pain	1/17 (5.9%)	1	4/17 (23.5%)	4
Skin chapped	1/17 (5.9%)	1	0/17 (0%)	0

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.