Otitis Media ChronicPhase 2/3NCT04761562
Use of Autologous Plasma Rich in Platelets and Extracellular Vesicles in the Surgical Treatment of Chronic Middle Ear Infections
A Phase 2/3 study testing Platelet- and extracellular vesicle-rich plasma in people with Otitis Media Chronic and Tympanic Membrane Perforation, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
This clinical study evaluates the efficacy of the autologous blood-derived product called platelet- and extracellular vesicle-rich plasma as a supplement to the surgical treatment of chronic tympanic membrane perforations. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Otitis Media Chronic, Tympanic Membrane Perforation
- What is being tested?
- Platelet- and extracellular vesicle-rich plasma
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteSlovenia
- Study dates
- 14 Feb 2021to 30 Sep 2023
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- tympanic membrane,
- dry middle ear cavity,
- absence of exclusion criteria.
Who cannot join
- signs of cholesteatoma,
- anemia,
- thrombocytopenia,
- chronic use of immunomodulatory agents and / or antimicrobials,
- malignancy in the ear area,
- systemic infectious disease,
Show all 9Show fewer
- autoimmune disease,
- inability and / or refusal of the patient to participate in the research,
- pregnancy and / or breast-feeding.
Trial locations and contacts
1 site in 1 country.
Slovenia1 site, 1 recruiting
- Recruiting
University Medical Centre Ljubljana
Ljubljana, 1000
Nejc Steiner, MD, +38615223280, nejc.steiner@kclj.si
About this study
Official title: Use of Autologous Plasma Rich in Platelets and Extracellular Vesicles in the Surgical Treatment of Chronic Otitis Media
This clinical study evaluates the efficacy of the autologous blood-derived product called platelet- and extracellular vesicle-rich plasma as a supplement to the surgical treatment of chronic tympanic membrane perforations.
Half of the participants will be treated with standard surgical procedure called tympanoplasty and addition of platelet- and extracellular vesicle-rich plasma. Another half will be treated with only the standard tympanoplasty.
Read the detailed description
The study is designed to be mono-centric, prospective, double-blind, parallel, uniformly randomised, controlled, with a fixed sample.
The purpose of the study is to determine whether autologous platelet- and extracellular vesicle-rich plasma (PVRP) made from peripheral venous blood, promotes healing of tympanic membrane perforations, improves hearing and quality of life after surgical procedure called tympanoplasty.
Tympanoplasty is a surgical procedure in which the surgeon refreshes the edges of the perforation of the eardrum and thus encourage re-healing of the eardrum. The tympanic membrane lies in the air, thus a tissue (muscle fascia, perichondrium, fat or cartilage) has to be put underneath the perforation and eardrum remnant. This then serves as a guide for the newly formed tympanic cells can outgrow the perforation.
Patients attending outpatient examinations will be included in the study if they meet the inclusion criteria. Included patients will be randomised in two groups.
Patients from the control group will be treated with a standard surgical treatment - tympanoplasty. The surgical procedure for the patients from the treatment group will be the same as for the control group, for the exception that PVRP will be added around the tympanic membrane remnant. PVRP will be activated inside (endogenous) and outside (exogenous) the body.
Postoperatively patients will be assessed at examinations using an endoscope, otomicroscope, Chronic otitis media questionnaire and tests of hearing and balance. Laboratory blood tests will determine the presence of possible inflammation and assess the composition of the preparation.
Research hypotheses
- Hypothesis 1: In the group of patients treated with platelet-rich plasma and extracellular vesicles, the proportion of healed tympanic surfaces in terms of initial perforation will be higher than in patients treated without platelet-rich plasma and extracellular vesicles.
- Hypothesis 2: In the group of patients treated with platelet-rich plasma and extracellular vesicles, complete healing of the tympanic membrane will occur to a greater extent than in patients treated without platelet-rich plasma and extracellular vesicles.
- Hypothesis 3: In the group of patients treated with platelet-rich plasma and extracellular vesicles, hearing improvement will be greater than in patients treated with platelet-rich plasma and extracellular vesicles.
- Hypothesis 4: The quality of life of patients with larger perforations assessed with the COMQ-12 questionnaire will be lower than in patients treated without platelet-rich plasma and extracellular vesicles.
- Hypothesis 5: The quality of life assessed by the COMQ-12 questionnaire will be better in the group of patients treated with platelet-rich plasma and extracellular vesicles than in patients treated without platelet-rich plasma and extracellular vesicles.
- Being tested
- Platelet- and extracellular vesicle-rich plasma, Control group
- Keywords
- Tympanoplasty, Platelet-Rich Plasma
- Medical subject headings
- Tympanic Membrane Perforation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Platelet- and extracellular vesicle-rich plasmaDrug
PVRP will initially be applied to the gelatine sponge without prior exogenous activation, which will first be inserted into the middle ear cavity to support the reconstructed tympanic membrane. The remainder of the PVRP will then be exogenously activated with calcium chloride. Gel rich with platelets and extracellular vesicles will be created and applied on top of the reconstructed tympanic membrane. Finally, the external auditory canal will be filled with pieces of gelatine sponge soaked with PVRP.
Control groupProcedure or surgery
Also called Standard tympanoplasty
Edges of the tympanic membrane perforation will be refreshed and the tympanomeatal flap raised. Under the tympanic membrane perforation, a guide (fascia of the temporalis muscle, perichondrium, cartilage or fat) will be placed. An absorbent gelatin sponge will be placed under the guide and on the outer surface of the reconstructed tympanic membrane.
| Study group | Role | What they receive |
|---|---|---|
| Control group | Active comparator | Patients will be treated with a standard surgical procedure - tympanoplasty. Receives: Procedure: Control group |
| PVRP group | Experimental | Patients will be treated with a standard surgical procedure - tympanoplasty combined with PVRP. PVRP will be applied to the reconstructed tympanic membrane. Receives: Drug: Platelet- and extracellular vesicle-rich plasma |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of tympanic membrane perforation size
The size of the tympanic membrane perforation will be expressed as proportion of the total surface area of the tympanic membrane. Number of pixels on an endoscopic photograph of the tympanic membrane will be measured with a computer program. The measured number of perforation pixels will be divided by the measured number of pixels of the entire tympanic membrane. The measurement will be performed by two doctors and the average value of the measured proportion of the drum surface used.
Measured: Baseline (1 day pre-operatively), 6 weeks, 3 months and 6 months after surgery.
Change in Chronic Otitis Media Questionnaire 12 score
- the unabbreviated scale title: Chronic Otitis Media Questionnaire 12
- the minimum and maximum values: 0, 60
- higher scores mean a worse outcome.
Sum score of Chronic Otitis Media Questionnaire 12 (COMQ-12), patient-reported health-related quality of life measure. Questionnaire consists of 12 questions, each question is scored from 0 to 5 points.
Measured: Baseline (1 day pre-operatively), 6 months after surgery.
Secondary outcomes (1)
Change in hearing threshold level
Pure tone audiometry will be done and pure tone average calculated from frequencies 125 to 8000 Herz.
Measured: Baseline (1 day pre-operatively), 6 weeks, 3 months and 6 months after surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start14 Feb 2021
- Primary completion30 Sep 2023 (estimated)
- Study completion30 Sep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Otitis Media ChronicStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ljubljana
- Responsible party
- Principal investigator, Nejc Steiner, University Medical Centre Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04761562
- Sponsor's protocol ID
- PVRPTY2021
- Status last verified
- Feb 2021
- First submitted
- 12 Feb 2021
- Last updated
- 21 Feb 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Vozel D., Božič D., Jeran M., Jan Z., Pajnič M., Pađen L., Uršič B., Iglič A., Kralj-Iglič V., Battelino S. 2020. Treatment with platelet- and extracellular vesicle-rich plasma in otorhinolaryngology-a review and future perspectives. V Advances in Biomembranes and Lipid Self-Assembly. Academic Press. https://doi.org/10.1016/bs.abl.2020.05.003
Vozel D, Steiner N, Bozanic Urbancic N, Mladenov D, Battelino S. Slovenian Cross-Cultural Adaptation and Validation of Health-Related Quality of Life Measures for Chronic Otitis Media (COMQ-12), Vertigo (DHI, NVI) and TINNITUS (THI). Zdr Varst. 2020 Jun 25;59(3):120-127. doi: 10.2478/sjph-2020-0016. eCollection 2020 Sep.
PubMed 32952712
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Autologous Plasma Rich in Platelets and Extracellular Vesicles in the Surgical Treatment of Chronic Otitis Media
- ClinicalTrials.gov ID
- NCT04761562
- Acronym / sponsor ID
- PVRPTY2021
- Keywords
- Tympanoplasty, Platelet-Rich Plasma
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Collaborators
- University of Ljubljana
- Study start
- 14 Feb 2021 (actual)
- Primary completion
- 30 Sep 2023 (estimated)
- Study completion
- 30 Sep 2023 (estimated)
- First posted
- 21 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical study evaluates the efficacy of the autologous blood-derived product called platelet- and extracellular vesicle-rich plasma as a supplement to the surgical treatment of chronic tympanic membrane perforations.
Half of the participants will be treated with standard surgical procedure called tympanoplasty and addition of platelet- and extracellular vesicle-rich plasma. Another half will be treated with only the standard tympanoplasty.
Detailed description
The study is designed to be mono-centric, prospective, double-blind, parallel, uniformly randomised, controlled, with a fixed sample.
The purpose of the study is to determine whether autologous platelet- and extracellular vesicle-rich plasma (PVRP) made from peripheral venous blood, promotes healing of tympanic membrane perforations, improves hearing and quality of life after surgical procedure called tympanoplasty.
Tympanoplasty is a surgical procedure in which the surgeon refreshes the edges of the perforation of the eardrum and thus encourage re-healing of the eardrum. The tympanic membrane lies in the air, thus a tissue (muscle fascia, perichondrium, fat or cartilage) has to be put underneath the perforation and eardrum remnant. This then serves as a guide for the newly formed tympanic cells can outgrow the perforation.
Patients attending outpatient examinations will be included in the study if they meet the inclusion criteria. Included patients will be randomised in two groups.
Patients from the control group will be treated with a standard surgical treatment - tympanoplasty. The surgical procedure for the patients from the treatment group will be the same as for the control group, for the exception that PVRP will be added around the tympanic membrane remnant. PVRP will be activated inside (endogenous) and outside (exogenous) the body.
Postoperatively patients will be assessed at examinations using an endoscope, otomicroscope, Chronic otitis media questionnaire and tests of hearing and balance. Laboratory blood tests will determine the presence of possible inflammation and assess the composition of the preparation.
Research hypotheses
- Hypothesis 1: In the group of patients treated with platelet-rich plasma and extracellular vesicles, the proportion of healed tympanic surfaces in terms of initial perforation will be higher than in patients treated without platelet-rich plasma and extracellular vesicles.
- Hypothesis 2: In the group of patients treated with platelet-rich plasma and extracellular vesicles, complete healing of the tympanic membrane will occur to a greater extent than in patients treated without platelet-rich plasma and extracellular vesicles.
- Hypothesis 3: In the group of patients treated with platelet-rich plasma and extracellular vesicles, hearing improvement will be greater than in patients treated with platelet-rich plasma and extracellular vesicles.
- Hypothesis 4: The quality of life of patients with larger perforations assessed with the COMQ-12 questionnaire will be lower than in patients treated without platelet-rich plasma and extracellular vesicles.
- Hypothesis 5: The quality of life assessed by the COMQ-12 questionnaire will be better in the group of patients treated with platelet-rich plasma and extracellular vesicles than in patients treated without platelet-rich plasma and extracellular vesicles.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Active comparator | Procedure: Control groupPatients will be treated with a standard surgical procedure - tympanoplasty. |
| PVRP group | Experimental | Drug: Platelet- and extracellular vesicle-rich plasmaPatients will be treated with a standard surgical procedure - tympanoplasty combined with PVRP. PVRP will be applied to the reconstructed tympanic membrane. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- tympanic membrane,
- dry middle ear cavity,
- absence of exclusion criteria.
Key exclusion criteria (9 listed)
- signs of cholesteatoma,
- anemia,
- thrombocytopenia,
- chronic use of immunomodulatory agents and / or antimicrobials,
- malignancy in the ear area,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Platelet- and extracellular vesicle-rich plasmaPVRP will initially be applied to the gelatine sponge without prior exogenous activation, which will first be inserted into the middle ear cavity to support the reconstructed tympanic membrane. The remainder of the PVRP will then be exogenously activated with calcium chloride. Gel rich with platelets and extracellular vesicles will be created and applied on top of the reconstructed tympanic membrane. Finally, the external auditory canal will be filled with pieces of gelatine sponge soaked with PVRP. | Drug | PVRP group |
| Control groupAlso: Standard tympanoplastyEdges of the tympanic membrane perforation will be refreshed and the tympanomeatal flap raised. Under the tympanic membrane perforation, a guide (fascia of the temporalis muscle, perichondrium, cartilage or fat) will be placed. An absorbent gelatin sponge will be placed under the guide and on the outer surface of the reconstructed tympanic membrane. | Procedure or surgery | Control group |
Primary outcome
Change of tympanic membrane perforation size
Time frame: Baseline (1 day pre-operatively), 6 weeks, 3 months and 6 months after surgery.
The size of the tympanic membrane perforation will be expressed as proportion of the total surface area of the tympanic membrane. Number of pixels on an endoscopic photograph of the tympanic membrane will be measured with a computer program. The measured number of perforation pixels will be divided by the measured number of pixels of the entire tympanic membrane. The measurement will be performed by two doctors and the average value of the measured proportion of the drum surface used.
Change in Chronic Otitis Media Questionnaire 12 score
Time frame: Baseline (1 day pre-operatively), 6 months after surgery.
* the unabbreviated scale title: Chronic Otitis Media Questionnaire 12 * the minimum and maximum values: 0, 60 * higher scores mean a worse outcome. Sum score of Chronic Otitis Media Questionnaire 12 (COMQ-12), patient-reported health-related quality of life measure. Questionnaire consists of 12 questions, each question is scored from 0 to 5 points.
1 secondary outcome
Change in hearing threshold level
Time frame: Baseline (1 day pre-operatively), 6 weeks, 3 months and 6 months after surgery.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2021.
- BackgroundVozel D., Božič D., Jeran M., Jan Z., Pajnič M., Pađen L., Uršič B., Iglič A., Kralj-Iglič V., Battelino S. 2020. Treatment with platelet- and extracellular vesicle-rich plasma in otorhinolaryngology-a review and future perspectives. V Advances in Biomembranes and Lipid Self-Assembly. Academic Press. https://doi.org/10.1016/bs.abl.2020.05.003
- Background: PubMed 32952712Vozel D, Steiner N, Bozanic Urbancic N, Mladenov D, Battelino S. Slovenian Cross-Cultural Adaptation and Validation of Health-Related Quality of Life Measures for Chronic Otitis Media (COMQ-12), Vertigo (DHI, NVI) and TINNITUS (THI). Zdr Varst. 2020 Jun 25;59(3):120-127. doi: 10.2478/sjph-2020-0016. eCollection 2020 Sep.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Platelet- and extracellular vesicle-rich plasma in people with Otitis Media Chronic and Tympanic Membrane Perforation, run by University Medical Centre Ljubljana at 1 site in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nejc Steiner, MD (+38615223280, nejc.steiner@kclj.si), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of tympanic membrane perforation size (time frame: Baseline (1 day pre-operatively), 6 weeks, 3 months and 6 months after surgery.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04761562, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2021.