Efficacy of Platelet- and Extracellular Vesicle-rich Plasma in Chronic Postsurgical Temporal Bone Inflammations

Study Overview
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Brief Summary
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This clinical study evaluates the efficacy of the autologous blood-derived product called platelet- and extracellular vesicle-rich plasma (PVRP) for the treatment of chronically inflamed post-surgical temporal bone cavities. Half of the participants will be treated with platelet- and extracellular vesicle-rich plasma and another half with standard nonsurgical measures.

Detailed Description
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The hypothesis of this study is that platelet- and extracellular vesicle-rich plasma (PVRP) may be efficient in the treatment of chronically inflamed post-surgical temporal bone cavities. Platelet-rich plasma (PRP) is a well-known autologous blood-derived product with favourable immune, haemostatic and regenerative effects. It has been used in various medical fields including otorhinolaryngology. In fact, PRP contains important concentrations of extracellular vesicles (EV) which are the main contributors to PRP effects. For that reason, PRP can be identified as platelet- and extracellular vesicle-rich plasma (PVRP). In this study, PVRP will be prepared by a unique non-commercial 2-step centrifugation protocol developed by this study researchers. A radical cavity is a large post-surgical temporal bone cavity due to removal of the posterior external ear canal wall in open-technique cholesteatoma surgery. This technique is performed in approximately 40 per cent of cholesteatoma surgery. Radical cavities become inflamed in 3-20 per cent, which leads to the formation of granulation tissue and multiple suppurative periods. The large spectrum of surgical and nonsurgical treatment options have been applied to reduce patient discomfort. This significantly worsens the patients' quality of life and puts a significant burden on health care. Due to the knowledge of local immune response mechanisms in moist radical cavities and exhausted treatment options, new conservative treatment options have been researched. PVRP could present a promising treatment option for chronically inflamed radical cavities based on published preclinical and clinical studies. PVRP will be administered to chronically inflamed radical cavities via PVRP-soaked ear wicks.

Official Title
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Efficacy of Platelet- and Extracellular Vesicle-rich Plasma for the Treatment of Chronically Inflamed Post-surgical Temporal Bone Cavities: a Randomised Controlled Clinical Study

Conditions
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Otitis Media Chronic, Temporal Bone

Intervention / Treatment
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* Drug: Platelet- and extracellular vesicle-rich plasma
* Drug: Standard conservative treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: chronic otitis media, defined as a presence of at least 1 of the following: visible ear discharge, indirect signs of ear discharge (e.g. on a pillow, clothes), ear itching, the sensation of ear fullness, clinical signs of acute exacerbation of chronic otitis media during an otomicroscopic examination. non-cholesteatomatous chronic otitis media despite prior standard conservative treatment non-cholesteatomatous chronic otitis media despite prior surgical treatment Exclusion Criteria: the presence or suspicion of cholesteatoma infection of venepuncture site pregnancy breastfeeding long-term treatment with antimicrobial drugs long-term treatment with immunosuppressant drugs the presence of systemic infectious disease the presence of an autoimmune disease the presence of cancer receiving other types of experimental treatment for chronic otitis media

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
Interventional Model Description: Participants treated with PVRP will receive PVRP-soaked ear wicks at the day of recruitment, additionally 1 month later and then followed-up twice in 1-month intervals. Participants not treated with PVRP will be treated with standard conservative nonsurgical measures with the same follow-up time.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PVRP treated participants<br>Participants will receive PVRP in the chronically inflamed radical cavity at the baseline evaluation (day 0) and 1 month later (1. follow-up). There will be 2 additional follow-ups with a 1-month interval. | Drug: Platelet- and extracellular vesicle-rich plasma<br>* ear wick soaked in platelet- and extracellular vesicle-rich plasma<br>|
| Active Comparator: Standardly treated participants<br>Participants will receive standard conservative measures for the chronically inflamed radical cavity at the baseline evaluation (day 0), 1 month later (1. follow-up), 2 months later (2. follow-up) and 3 months later (3. follow-up). | Drug: Standard conservative treatment<br>* standard conservative measures, including antimicrobials, antiseptics and aural toilette for treating a chronically inflamed radical cavity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Inflammation Surface Area. | The inflamed tissue in the postoperative temporal bone cavity was observed and photographed otomicroscopically. Then the surface area of the inflamed tissue was determined by using ZEN 3.0 blue edition software(©Carl Zeiss Microscopy GmbH, 2019). Values in square millimetres were transformed to the ratios of the inflamed surface area according to the baseline surface area. The baseline surface area values are therefore 100% for each case or participant. | Baseline, 1 month, 2 months and 3 months after baseline | 
| Change in Chronic Otitis Media Questionnaire 12 Score | Sum score of Chronic Otitis Media Questionnaire 12 (COMQ-12), patient-reported health-related quality of life measure. Each question is scored from 0 to 5 points, therefore the minimum score value is 0 and the maximum 60. A higher score means worse chronic otitis media-related quality of life. A higher change in COMQ-12 score means a better treatment outcome. | Baseline, 1 month, 2 months and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bacterial Presence | The microbiological analysis included incubation of smear samples to cultivate bacteria, present in postsurgical temporal bone cavity inflammation. Microscopical analyses of colonies were performed to identify the presence of bacteria. Bacteria were absent if no colonies were identified. | Baseline, 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Otitis Media, Mastoidectomy, Wound Healing, Platelet-Rich Plasma, Extracellular Vesicles, Cholesteatoma, Regenerative Medicine