Use of Autologous Plasma Rich in Platelets and Extracellular Vesicles in the Surgical Treatment of Chronic Middle Ear Infections

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.

Study Overview

• Status: Recruiting
• Conditions: Tympanic Membrane Perforation; Otitis Media Chronic
• Intervention / Treatment: Procedure: Control group; Drug: Platelet- and extracellular vesicle-rich plasma

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Nejc Steiner, MD; Phone Number: +38615223280; Email: nejc.steiner@kclj.si
• Study Contact Backup: Name: Saba Battelino, PhD, MD; Phone Number: +38615228307; Email: saba.battelino@kclj.si

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Recruiting
    • University Medical Centre Ljubljana
    • Contact: Nejc Steiner, MD; Phone Number: +38615223280; Email: nejc.steiner@kclj.si

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Control group; Patients will be treated with a standard surgical procedure - tympanoplasty.	Procedure: Control group; 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.; Other Names: Standard tympanoplasty
EXPERIMENTAL: PVRP group; Patients will be treated with a standard surgical procedure - tympanoplasty combined with PVRP. PVRP will be applied to the reconstructed tympanic membrane.	Drug: Platelet- and extracellular vesicle-rich plasma; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Baseline (1 day pre-operatively), 6 months after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hearing threshold level	Pure tone audiometry will be done and pure tone average calculated from frequencies 125 to 8000 Herz.	Baseline (1 day pre-operatively), 6 weeks, 3 months and 6 months after surgery.

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Collaborators: University of Ljubljana

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 14, 2021
• Primary Completion (ANTICIPATED): September 30, 2023
• Study Completion (ANTICIPATED): September 30, 2023

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (ACTUAL): February 21, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Platelet-Rich Plasma; Tympanoplasty
• Additional Relevant MeSH Terms: Wounds and Injuries; Otorhinolaryngologic Diseases; Ear Diseases; Otitis; Otitis Media; Tympanic Membrane Perforation
• Other Study ID Numbers: PVRPTY2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No