Effect of Pleuran on the Clinical Course of Patients With Chronic Rhinosinusitis

Participants: Newly diagnosed patients over 12 years of age with a diagnosis of chronic rhinosinusitis without nasal polyps meeting the inclusion criteria.

Sites: 5; Czech republic (2) and Slovakia (3) Study duration: 12 moths: 3 months treatment + 3 months follow-up + 3 months treatment + 3 months follow-up

Randomization:

* Control group: Standard of care treatment according to EPOS guidelines (INCS and saline irrigation)
* Active group: Standard of care treatment according to EPOS guidelines (INCS and saline irrigation) + Imunoglukan P4H® capsules (IMG® 100 mg + Vitamin C 100 mg in 1 capsule)

Participants will:

* take standard of care treatment according to EPOS guidelines.
* take Imunoglukan P4H® every day for 3 months then there will be three months follow-up (without Imunoglukan P4H®), this cycle will be repeated twice (only participants in the active group).
* visit the clinic for control visits one month after the study initiation and then every three months during 12 months study period (SNOT-22 questionnaire, VAS scale for evaluation of CRS severity by treating physician, Swab from the upper aerodigestive tract, rhinoendoscopic examination)
* keep a diary of their symptoms (incidence and duration of CRS exacerbations and acute respiratory infections, use of antibiotics, use of intranasal corticosteroids and other symptomatic treatments)
* record number of emergency department visits, hospitalizations, doctor visits and missed work/school days.
* record incidence of potential adverse events

• Imunoglukan P4H® capsules (Dietary supplement): 1 capsule contains 100 mg of IMG® and 100 mg of vitamin C

Primary outcomes

• change in the number of chronic rhinosinusitis exacerbations [from enrolment (day 1) through study completion (12 months) at each study visit (every 3 months)]
• change in use of antibiotics [from enrolment (day 1) through study completion (12 months) at each study visit (every 3 months)]
• change in use of intranasal corticosteroids [from enrolment (day1) through study completion (12 months) at each study visit (every 3 months)]
• change in the incidence of respiratory tract infections [from enrolment (day 1) through study completion (12 months) at each study visit (every 3 months)]

Secondary outcomes

• change in the severity of chronic rhinosinusitis according to Rhinoendoscopic examination [from enrolment (day 1) through study completion (12 months) at each study visit (every 3 months)]: Rhinoendoscopic examination performed by physician (assessed parameters included: polyps, oedema, nasal mucosa secretion). Each parameter (polyps, oedema, nasal mucosa secretion) will be assessed in a 3 or 4-point scale. The examination is conducted for each nostril, with the total score being the sum of all evaluated parameters. Assessment Scale (3-point: 0, 1, 2) * Polyps assessement scale (4-point: 0, 1, 2, 3): 0 = None; 1 = In middle meatus; 2 = Beyond middle meatus; 3 = complete closure of the nasal meatus. * Oedema assessement scale (3-point: 0, 1, 2): 0 = Absent; 1 = Mild; 2 = Severe. * Nasal mucosa secretion assessement scale (3-point: 0, 1, 2): 0 = None; 1 = Clear/thin; 2 = Thick/purulent
• change in the severity of chronic rhinosinusitis according to VAS scale [from enrolment (day 1) through study completion (12 months) at each study visit (every 3 months)]: VAS scale (patient-reported measure of symptom severity using a 0 to 10 scale, with 0 being no symptoms and 10 being the most severe)
• change in the severity of chronic rhinosinusitis according to Sino-Nasal Outcome Test [from enrolment (day 1) through study completion (12 months) at each study visit (every 3 months)]: Sino-Nasal Outcome Test (SNOT-22 Questionnaire - covers a broad range of health-related QoL problems, including physical problems, functional limitations and emotional consequences. The questionnaire is converted into a score of 0-110, with higher scores indicating a greater impact on QoL.) - patient reported questionnaire
• change in microbiological cultivation in the upper aerodigestive tract [from enrolment (day 1) through study completion (12 months) at each study visit (every 3 months)]: Examination of microbiome changes was assessed by collecting nasal and oropharyngeal swabs, followed by microbiome analysis.
• Incidence of Treatment-Emergent Adverse Events [from enrolment (day 1) through study completion (12 months) at each study visit (every 3 months)]: Safety was monitored by number of participants with treatment-related adverse events. Tolerability was assessed by product acceptance and adherence to study treatment.

Sex: All, ages: 12 Years to any

Inclusion Criteria:

* age over 12 years
* signed informed consent
* patients with newly diagnosed CRS without nasal polyps (meeting the criteria for the definition of CRS according to EPOS)
* patients without anatomical abnormalities causing nasal obstruction (nasal septal deformity, nasal turbinate hyperplasia, tumours, craniofacial deformities)
* patients able and willing to complete the questionnaires, undergo rhinoendoscopic examination, upper aerodigestive tract swabs and follow-up outpatient examinations

Exclusion Criteria:

* refused informed consent
* inability/unwillingness to complete the questionnaire, undergo rhinoendoscopic examination, upper aerodigestive tract swabs, follow-up outpatient examinations
* inability/unwillingness to use the product in accordance with the research protocol and compliance < 75%
* patients with protracted rhinosinusitis, exacerbations rhinosinusitis with the presence of an asymptomatic period
* patients with CRS during conservative treatment
* patients with CRS after previous surgical treatment
* patients with grade 3 nasal polyps
* patients with adenoid vegetations/persistent pharyngeal tonsils (especially if children are included in the study)
* patients with CRS with anatomical abnormalities causing nasal obstruction (septal deformity, turbinate hyperplasia, tumors, craniofacial abnormalities)
* patients with significant immunodeficiency
* patients with mucociliary transport disorders (e.g. cystic fibrosis, primary ciliary dyskinesia)
* patients taking other immunomodulating preparations regularly and for a long time (e.g. beta-glucans, Preventan, vitamins C and D, probiotics, Echinacea, bacterial lysates, etc.)
* pregnant and breastfeeding women

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• Study Protocol (PDF, 2022-10-05)

• Barbora Uhliarová, MD., PhD., MPH, Principal investigator, ORL department, F.D. Roosevelt University Hospital with Policlinic, Banská Bystrica, Slovensko, Slovakia, 97517