PRF With Topical Antibiotics or Antiseptics in Chronical Wounds Version 1.4

Study Overview
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Brief Summary
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Platelet rich fibrin (PRF) is a new therapy option for chronic wounds with yet unproven therapeutic efficacy. This randomised controlled trial aims to provide evidence of the efficacy of PRF as monotherapy as well as a growth promoting carrier matrix for antimicrobial compounds. The investigators therefore designed a four armed trial with three PRF arms which are compared to each other as well as to an active comparator. The treatment arms are as follows: Study arm 1: PRF with amikacin and teicoplanin Study arm 2: PRF with placebo (0.9% sodium chloride) Study arm 3: PRF with PHMB (polyhexanid) plus Macrogolol (Lavasorb®) Study arm 4: Acticoat 7® wound dressing as active control Patients with infected chronic wounds may be included in this trial. Infection shall be diagnosed by an experienced senior infectious diseases specialist. Patients with untreated peripheral vascular occlusive disease as defined by an ABI (ancle brachial index) of < 0,7 are excluded from the trial as are patients with an uncontrolled diabetes mellitus or patients who have not received sufficient treatment for a diabetic foot syndrome. Any underlying illness will be treated following standard of care. In case of chronic venous insufficiency four-layered compression bandages will be applied each visit if tolerated by the patient. Alternatively compression stockings (Class III) are permitted. This is mentioned as Disease specific treatment in the protocol. Patients will receive treatment for 56 days. After 28 and 56 days the wound surface will be compared to the baseline. Infection parameters (c-reactive protein and leucocyte count) will be measured weekly. Evaluation of systemic antimicrobial therapy will be performed at each visit. Systemic antimicrobial therapy is started at the discretion of a senior infectious diseases specialist.

Official Title
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Platelet Rich Fibrin in Combination With Topical Antibiotics or Antiseptics in the Treatment of Chronic Wounds - a Prospective, Randomized, Active Controlled, Double Blind Pilot Trial With an Observer-blinded Control Group

Conditions
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Chronic Skin Ulcer

Intervention / Treatment
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* Drug: PRF mixed with amikacin and teicoplanin
* Drug: PRF mixed with PHMB plus Macrogolol
* Drug: PRF plus normal saline
* Other: Silver gauze


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged over 18 who are able to give informed consent Chronic venous ulcer with localized non-systemic soft-tissue infection diagnosed by senior infectious diseases specialist based on US FDA Guidance for Industry Chronic cutaneous ulcer and burn wounds June 2006: slough and necrotic tissue exsudate smell inflammation presence of granulation tissue pain Wound size ≥ 5 cm2 and < 200 cm2 Exclusion Criteria: Non-treated diabetes mellitus, HbA1c > 12 mg/dl Non treated (orthopaedic shoe) diabetic foot syndrome ABI < 0,7 Wound size 15 cm2 and > 200 cm2 CRP > 5 mg/dl Leucocytes > 15.000 /μl Infection of another site Infection of the ulcer with a pathogen with inherent resistance to amikacin and teicoplanin Known osteomyelitis Known erysipelas Known phlegmon Complicated deep tissue infection not solely treatable with PRF plus antimicrobial therapy in the opinion of a senior infectious diseases specialist Planned systemic antimicrobial therapy Active viral hepatitis (A/B/C) or active HIV infection or active syphilis Increased sensitivity to amikacin or teicoplanin, PHMB or macrogolol Increased sensitivity to tramexanic acid or batroxobin Presence of neoplastic growth in the ulcer Thrombocytopenic patients (<150.000 G/L) Haemoglobin < 95 g/L Known pregnancy or lactation Severe renal impairment (creatinine clearance <30 ml/min) History or clinical signs of impairment of the cochlea or vestibularis system Neuromuscular diseases (i.e. Myasthenia gravis, Parkinson's disease) Aminoglycoside treatment less than four weeks before inclusion Other reasons opposing the study participation on the discretion of the investigators

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study arm 1 - PRF plus amikacin and teicoplanin<br>PRF mixed with amikacin and teicoplanin is sprayed on the patients' ulcer | Drug: PRF mixed with amikacin and teicoplanin<br>* PRF, mixed with amikacin and teicoplanin is applied to the chronic ulcer<br>* Other names: PRF plus amikacin/teicoplanin;|
| Experimental: Study arm 2 - PRF plus normal saline<br>PRF mixed with normal saline is sprayed on the patients' ulcer | Drug: PRF plus normal saline<br>* PRF as a monosubstance plus sodium chloride 0.9% is applied to the chronic ulcer<br>* Other names: PRF plus sodium chloride 0.9%;|
| Experimental: Study arm 3 - PRF mixed with PHMB plus Macrogolol<br>PRF mixed with polyhexanide and macrogolol is sprayed on the patients' ulcer | Drug: PRF mixed with PHMB plus Macrogolol<br>* PRF, mixed with Lavasorb is applied to the chronic ulcer<br>* Other names: PRF plus Lavasorb;|
| Active Comparator: Study arm 4 - Acticoat 7<br>A silver gauze (Acticoat 7®) is applied to the patients' ulcer | Other: Silver gauze<br>* Acticoat 7 silver wound dressing is applied to the chronic ulcer<br>* Other names: Acticoat 7;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| reduction in wound area |  | day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients in necessity to initiate systemic antimicrobial therapy based on the opinion of a senior infectious disease consultant arises (subjective assessment based on wound inflammation, serum c-reactive protein levels and leucocyte count) |  | day 0, 7, 14, 21, 28, 35, 42, 49, 56 | 
| Elevation of C-reactive protein over 7 mg/dl (normal value 0.5 mg/dl) |  | day 0, 7, 14, 21, 28, 35, 42, 49, 56 | 
| time to sterility of the wound |  | day 0, 7, 14, 21, 28, 35, 42, 49, 56 | 
| Relative wound volume and wound area reduction |  | on day 28 and 56 | 
| Occurrence of drug resistant bacteria in the wound |  | day 0, 7, 14, 21, 28, 35, 42, 49, 56 | 
| Occurrence of drug resistant bacteria in a swab of the tissue surrounding the wound or a Z-swab of the torso |  | on day 28 and 56 |