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| Name | Class |
|---|---|
| University of Ljubljana | OTHER |
| University of Ljubljana, Faculty of Medicine | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PVRP treated participants | Experimental | 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. |
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| Standardly treated participants | Active Comparator | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Platelet- and extracellular vesicle-rich plasma | Drug | ear wick soaked in platelet- and extracellular vesicle-rich plasma |
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Saba Battelino, MD, PhD | Department of Otorhinolaryngology and Cervicofacial Surgery, UMC Ljubljana | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Centre Ljubljana | Ljubljana | 1000 | Slovenia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28156006 | Background | Vozel D, Ursic B, Krek JL, Stukelj R, Kralj-Iglic V. Applicability of extracellular vesicles in clinical studies. Eur J Clin Invest. 2017 Apr;47(4):305-313. doi: 10.1111/eci.12733. Epub 2017 Feb 28. | |
| Background | Uršič B, Vozel D, Šuštar V, Kocjančič B, Dolinar D, Kralj-Iglič V. Extracellular Vesicles from Platelet-Rich Plasma as Conveyors of Regeneration Potential in Orthopedics. J Hematol Thromboembolic Dis 2(5), 2014. | ||
| 34307321 |
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IPD relevant for the results will be shared
Data will be available from the beginning of the study until the conclusion.
Access for the data affecting results will be provided. Access to this data will be provided by the central contact person or central contact backup. No personal identification information will be provided.
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After random allocation 1 patient allocated to the group treated with standard conservative measures refused to participate in the study.
25 participants with chronic postoperative temporal bone cavity inflammation were recruited at the tertiary otorhinolaryngology referral centre between February- March 2020. In this period the list of patients was created based on examinations and documentation review. 2 participants had bilateral involvement, therefore 27 cases were recruited.
| ID | Title | Description |
|---|---|---|
| FG000 | PVRP Treated Participants | Participants received platelet- and extracellular vesicle-rich plasma (PVRP)-soaked ear wick in the chronic postoperative temporal bone cavity inflammation at the baseline evaluation (i.e., 1. check-up) and 1 month later (i.e., 2. check-up). Two additional check-ups were performed in a 1-month interval. The aural toilet was applied at each check-up. No other treatment measures were applied Platelet- and extracellular vesicle-rich plasma: ear wick soaked in platelet- and extracellular vesicle-rich plasma |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 1, 2020 | Jul 17, 2020 |
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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.
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A person unaware of the participants and their random allocation will measure inflammation area with computer software provided by ZEN Lite, Zeiss.
| Standard conservative treatment | Drug | standard conservative measures, including antimicrobials, antiseptics and aural toilette for treating a chronically inflamed radical cavity. |
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| Result |
| Vozel D, Bozic D, Jeran M, Jan Z, Pajnic M, Paden L, Steiner N, Kralj-Iglic V, Battelino S. Autologous Platelet- and Extracellular Vesicle-Rich Plasma Is an Effective Treatment Modality for Chronic Postoperative Temporal Bone Cavity Inflammation: Randomized Controlled Clinical Trial. Front Bioeng Biotechnol. 2021 Jul 7;9:677541. doi: 10.3389/fbioe.2021.677541. eCollection 2021. |
| FG001 | Standardly Treated Participants | Participants were treated with standard conservative measures, including antimicrobials, antiseptics and aural toilette at 1., 2., 3. and 4. check-up. Standard conservative treatment: standard conservative measures, including antimicrobials, antiseptics and aural toilette for treating a chronically inflamed radical cavity. |
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| 2. Check-up | 1 month after the baseline evaluation |
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| 3. Check-up | 2 months after baseline evaluation |
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| COMPLETED | 4. check-up (i.e., 3. months after the baseline evaluation) |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | PVRP Treated Participants | Participants received platelet- and extracellular vesicle-rich plasma (PVRP)-soaked ear wick in the chronic postoperative temporal bone cavity inflammation at the baseline evaluation (i.e., 1. check-up) and 1 month later (i.e., 2. check-up). Two additional check-ups were performed in a 1-month interval. The aural toilet was applied at each check-up. No other treatment measures were applied Platelet- and extracellular vesicle-rich plasma: ear wick soaked in platelet- and extracellular vesicle-rich plasma |
| BG001 | Standardly Treated Participants | Participants were treated with standard conservative measures, including antimicrobials, antiseptics and aural toilette at 1., 2., 3. and 4. check-up. Standard conservative treatment: standard conservative measures, including antimicrobials, antiseptics and aural toilette for treating a chronically inflamed radical cavity. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| case |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years | Participants |
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| Sex: Female, Male | Count of Participants | Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants | Participants |
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| Region of Enrollment | Number | participants | Participants |
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| Quality of life (i.e., COMQ-12 sum score) | Quality of life, related to chronic postoperative temporal bone cavity inflammation was measured with Slovenian version of COMQ-12 (Chronic Otitis Media Questionnaire-12). The questionnaire consists of 12 questions, scored 0-5. The higher sum score signifies the worse quality of life. The minimum sum score is 0 and the maximum is 60. | Mean | Standard Deviation | scores on a scale | Participants |
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| Presence of bacteria in temporal bone cavity | Bacteria were identified in the temporal bone cavity by microbiological examinations of temporal bone cavity swabs. | Count of Units | case | case |
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| Presence of fungi in temporal bone cavity | Fungi were identified in the temporal bone cavity by microbiological examinations of temporal bone cavity swabs. | Count of Units | case | case |
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| Comorbidities | Count of Participants | Participants | Participants |
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| Allergies | Count of Participants | Participants | Participants |
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| Regular medications | Presence or absence of regular medication intake. | Count of Participants | Participants | Participants |
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| Coagulopathy | Presence of coagulopathies, including medication-related coagulopathies. | Count of Participants | Participants | Participants |
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| Smoking | Count of Participants | Participants | Participants |
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| Alcohol intake | Count of Participants | Participants | Participants |
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| Time to treatment according to the study protocol | Time to treatment according to the study protocol refers to the time from the beginning of the complaints due to the chronic postoperative temporal bone cavity inflammation to the baseline evaluation. | Median | Full Range | years | case |
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| Time from otosurgery to treatment according to the study protocol | Time from otosurgery refers to the time from the last otological surgical procedure (i.e., due to the temporal bone disease which led to the chronic postoperative temporal bone cavity inflammation) to the baseline evaluation. | Data of time from otosurgery was unknown some cases. | Median | Full Range | years | case |
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| Underlying otological disease requiring otosurgical treatment | Count of Units | case | case |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | percentage of the baseline surface | Baseline, 1 month, 2 months and 3 months after baseline | case | case |
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| Primary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline, 1 month, 2 months and 3 months |
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| Secondary | 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. | Posted | Count of Units | case | Baseline, 2 months | case | case |
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Adverse events were monitored from the beginning of the trial to the last check-up, i.e. from the baseline evaluation and 4 months after (4. check-up). Therefore, the adverse effects were monitored for 4 months.
11 patients who received platelet- and extracellular vesicle-rich plasma (PVRP) and 11 who received standard conservative treatment measures were at risk for serious adverse events, all-cause mortality and other adverse events. PVRP-related adverse events were defined as worsening of chronic postsurgical temporal bone inflammation due to PVRP. The worsening was attributed to PVRP if worsening of the clinical picture occurred within three days after PVRP administration.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PVRP Treated Participants | Participants received platelet- and extracellular vesicle-rich plasma (PVRP)-soaked ear wick in the chronic postoperative temporal bone cavity inflammation at the baseline evaluation (i.e., 1. check-up) and 1 month later (i.e., 2. check-up). Two additional check-ups were performed in a 1-month interval. The aural toilet was applied at each check-up. No other treatment measures were applied Platelet- and extracellular vesicle-rich plasma: ear wick soaked in platelet- and extracellular vesicle-rich plasma | 0 | 11 | 0 | 11 | 0 | 11 |
| EG001 | Standardly Treated Participants | Participants were treated with standard conservative measures, including antimicrobials, antiseptics and aural toilette at 1., 2., 3. and 4. check-up. Standard conservative treatment: standard conservative measures, including antimicrobials, antiseptics and aural toilette for treating a chronically inflamed radical cavity. | 0 | 11 | 0 | 11 | 0 | 11 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Domen Vozel, M.D., Saba Battelino, M.D., PhD. | Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia. Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. | +386 (0)1 522 83 07 | domen.vozel@kclj.si |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 1, 2020 | Jul 31, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D010033 | Otitis Media |
| D002781 | Cholesteatoma |
| ID | Term |
|---|---|
| D010031 | Otitis |
| D004427 | Ear Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D007642 | Keratosis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D010976 | Platelet Count |
| ID | Term |
|---|---|
| D001772 | Blood Cell Count |
| D002452 | Cell Count |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D006403 | Hematologic Tests |
| D010979 | Platelet Function Tests |
| D008919 | Investigative Techniques |
| D002468 | Cell Physiological Phenomena |
| D001790 | Blood Physiological Phenomena |
| D002943 | Circulatory and Respiratory Physiological Phenomena |
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| >=65 years |
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