Clinical trial NCT04761562: Use of Autologous Plasma Rich in Platelets and Extracellular Vesicles in the Surgical Treatment of Chronic Middle Ear Infections
Official title: Use of Autologous Plasma Rich in Platelets and Extracellular Vesicles in the Surgical Treatment of Chronic Otitis Media
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Otitis Media Chronic
Tympanic Membrane Perforation
Keywords: Tympanoplasty
Platelet-Rich Plasma
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: University of Ljubljana
First posted: 2021-02-21
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* tympanic membrane,
* dry middle ear cavity,
* absence of exclusion criteria.

Exclusion Criteria:

* signs of cholesteatoma,
* anemia,
* thrombocytopenia,
* chronic use of immunomodulatory agents and / or antimicrobials,
* malignancy in the ear area,
* systemic infectious disease,
* autoimmune disease,
* inability and / or refusal of the patient to participate in the research,
* pregnancy and / or breast-feeding.

Primary outcomes:
measure: Change of tympanic membrane perforation size
timeFrame: Baseline (1 day pre-operatively), 6 weeks, 3 months and 6 months after surgery.
measure: Change in Chronic Otitis Media Questionnaire 12 score
timeFrame: Baseline (1 day pre-operatively), 6 months after surgery.
Secondary outcomes:
measure: Change in hearing threshold level
timeFrame: Baseline (1 day pre-operatively), 6 weeks, 3 months and 6 months after surgery.
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
Study officials:
References:
citation: 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
citation: 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.