Otitis Media Chronic, Temporal Bone
Conditions
Keywords
Otitis Media, Mastoidectomy, Wound Healing, Platelet-Rich Plasma, Extracellular Vesicles, Cholesteatoma, Regenerative Medicine
Brief summary
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
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.
Interventions
ear wick soaked in platelet- and extracellular vesicle-rich plasma
standard conservative measures, including antimicrobials, antiseptics and aural toilette for treating a chronically inflamed radical cavity.
Sponsors
University of Ljubljana
University of Ljubljana, Faculty of Medicine
University Medical Centre Ljubljana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
A person unaware of the participants and their random allocation will measure inflammation area with computer software provided by ZEN Lite, Zeiss.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inflammation Surface Area. | Baseline, 1 month, 2 months and 3 months after baseline | 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. |
| Change in Chronic Otitis Media Questionnaire 12 Score | Baseline, 1 month, 2 months and 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bacterial Presence | Baseline, 2 months | 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. |
Countries
Slovenia
Participant flow
Recruitment details
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.
Pre-assignment details
After random allocation 1 patient allocated to the group treated with standard conservative measures refused to participate in the study.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 11 |
| 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 | 11 |
| 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. | 11 |
| 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. | 13 |
| Total | 46 |
Baseline characteristics
| Characteristic | Standardly Treated Participants | PVRP Treated Participants | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 3 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 8 Participants | 13 Participants |
| Age, Continuous | 52 years STANDARD_DEVIATION 24 | 47 years STANDARD_DEVIATION 18 | 50 years STANDARD_DEVIATION 21 |
| Alcohol intake No regular alcohol intake | 4 Participants | 1 Participants | 5 Participants |
| Alcohol intake Regular alcohol intake | 7 Participants | 10 Participants | 17 Participants |
| Allergies Allergies absent | 7 Participants | 6 Participants | 13 Participants |
| Allergies Allergies present | 4 Participants | 5 Participants | 9 Participants |
| Coagulopathy Absence of coagulopathy | 10 Participants | 9 Participants | 19 Participants |
| Coagulopathy Presence of coagulopathy | 1 Participants | 2 Participants | 3 Participants |
| Comorbidities Comorbidities absent | 5 Participants | 5 Participants | 10 Participants |
| Comorbidities Comorbidities present | 6 Participants | 6 Participants | 12 Participants |
| Presence of bacteria in temporal bone cavity Bacteria identified | 12 case | 10 case | 22 case |
| Presence of bacteria in temporal bone cavity Bacteria not identified | 1 case | 1 case | 2 case |
| Presence of fungi in temporal bone cavity Fungi identified | 3 case | 2 case | 5 case |
| Presence of fungi in temporal bone cavity Fungi not identified | 10 case | 9 case | 19 case |
| Quality of life (i.e., COMQ-12 sum score) | 31 scores on a scale STANDARD_DEVIATION 10 | 32 scores on a scale STANDARD_DEVIATION 10 | 31 scores on a scale STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 11 Participants | 22 Participants |
| Region of Enrollment Slovenia | 11 participants | 11 participants | 22 participants |
| Regular medications Intake of regular medications | 6 Participants | 3 Participants | 9 Participants |
| Regular medications No intake of regular medications | 5 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
| Smoking Not smoking | 6 Participants | 9 Participants | 15 Participants |
| Smoking Smoking | 5 Participants | 2 Participants | 7 Participants |
| Time from otosurgery to treatment according to the study protocol | 14.3 years | 12.7 years | 13.8 years |
| Time to treatment according to the study protocol | 8.7 years | 7.4 years | 8.1 years |
| Underlying otological disease requiring otosurgical treatment External auditory canal cholesteatoma | 0 case | 1 case | 1 case |
| Underlying otological disease requiring otosurgical treatment External auditory canal squamous cell-carcinoma | 1 case | 0 case | 1 case |
| Underlying otological disease requiring otosurgical treatment Middle ear cholesteatoma | 12 case | 10 case | 22 case |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
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.
Time frame: Baseline, 1 month, 2 months and 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PVRP Treated Participants | Change in Chronic Otitis Media Questionnaire 12 Score | baseline evaluation (i.e., 1. check-up) | 32 score on a scale | Standard Deviation 10 |
| PVRP Treated Participants | Change in Chronic Otitis Media Questionnaire 12 Score | 2. check-up | 22 score on a scale | Standard Deviation 12 |
| PVRP Treated Participants | Change in Chronic Otitis Media Questionnaire 12 Score | 4. check-up | 17 score on a scale | Standard Deviation 10 |
| PVRP Treated Participants | Change in Chronic Otitis Media Questionnaire 12 Score | 3. check-up | 20 score on a scale | Standard Deviation 11 |
| Standardly Treated Participants | Change in Chronic Otitis Media Questionnaire 12 Score | 4. check-up | 32 score on a scale | Standard Deviation 8 |
| Standardly Treated Participants | Change in Chronic Otitis Media Questionnaire 12 Score | baseline evaluation (i.e., 1. check-up) | 31 score on a scale | Standard Deviation 10 |
| Standardly Treated Participants | Change in Chronic Otitis Media Questionnaire 12 Score | 2. check-up | 34 score on a scale | Standard Deviation 10 |
| Standardly Treated Participants | Change in Chronic Otitis Media Questionnaire 12 Score | 3. check-up | 33 score on a scale | Standard Deviation 11 |
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.
Time frame: Baseline, 1 month, 2 months and 3 months after baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PVRP Treated Participants | Change in Inflammation Surface Area. | Baseline evaluation | 100 percentage of the baseline surface | Standard Deviation 0 |
| PVRP Treated Participants | Change in Inflammation Surface Area. | 1 month | 43 percentage of the baseline surface | Standard Deviation 30 |
| PVRP Treated Participants | Change in Inflammation Surface Area. | 2 months | 36 percentage of the baseline surface | Standard Deviation 30 |
| PVRP Treated Participants | Change in Inflammation Surface Area. | 3 months | 36 percentage of the baseline surface | Standard Deviation 28 |
| Standardly Treated Participants | Change in Inflammation Surface Area. | 3 months | 150 percentage of the baseline surface | Standard Deviation 97 |
| Standardly Treated Participants | Change in Inflammation Surface Area. | Baseline evaluation | 100 percentage of the baseline surface | Standard Deviation 0 |
| Standardly Treated Participants | Change in Inflammation Surface Area. | 2 months | 144 percentage of the baseline surface | Standard Deviation 64 |
| Standardly Treated Participants | Change in Inflammation Surface Area. | 1 month | 135 percentage of the baseline surface | Standard Deviation 35 |
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.
Time frame: Baseline, 2 months
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| PVRP Treated Participants | Bacterial Presence | bacteria identified at the 2. check-up | 7 case |
| PVRP Treated Participants | Bacterial Presence | bacteria not identified at the 2. check-up | 4 case |
| Standardly Treated Participants | Bacterial Presence | bacteria identified at the 2. check-up | 9 case |
| Standardly Treated Participants | Bacterial Presence | bacteria not identified at the 2. check-up | 4 case |