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

NCT ID: NCT04761562

Last Updated: 2021-02-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-14
• Study Completion Date: 2023-09-30

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.

Conditions

Otitis Media Chronic; Tympanic Membrane Perforation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Control group

Patients will be treated with a standard surgical procedure - tympanoplasty.

Group Type: ACTIVE_COMPARATOR

Control group

Intervention Type: PROCEDURE

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.

PVRP group

Patients will be treated with a standard surgical procedure - tympanoplasty combined with PVRP. PVRP will be applied to the reconstructed tympanic membrane.

Group Type: EXPERIMENTAL

Platelet- and extracellular vesicle-rich plasma

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

Other Intervention Names

Standard tympanoplasty

Eligibility Criteria

Inclusion Criteria

• tympanic membrane,
• dry middle ear cavity,

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Ljubljana

OTHER

Sponsor Role: collaborator

University Medical Centre Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

Nejc Steiner

Principal Investigator, Resident of otorhinolaryngology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Medical Centre Ljubljana

Ljubljana, , Slovenia

Site Status: RECRUITING

Countries

Slovenia

Central Contacts

Nejc Steiner, MD

Role: CONTACT

nejc.steiner@kclj.si

+38615223280

Saba Battelino, PhD, MD

Role: CONTACT

saba.battelino@kclj.si

+38615228307

Facility Contacts

Nejc Steiner, MD

Role: primary

nejc.steiner@kclj.si

+38615223280

References

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

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 32952712 (View on PubMed)

Other Identifiers

PVRPTY2021

Identifier Type: -

Identifier Source: org_study_id