Clinical trial NCT05390255: Establishment of Precise Diagnosis and Treatment System for Refractory Chronic Rhinosinusitis
Official title: Establishment of Precise Diagnosis and Treatment System for Refractory Chronic Rhinosinusitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Sinusitis
Keywords: Refractory chronic sinusitis
Randomized Controlled Trial
Hormone therapy
Omalizumab
Biomarkers
Lead sponsor: Beijing Tongren Hospital
Sponsor class: OTHER
Collaborators: name: Peking Union Medical College Hospital
name: Beijing Hospital
First posted: 2022-05-25
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chronic rhinosinusitis that recurs after adequate surgery and conventional medical treatment is called refractory chronic rhinosinusitis (RCRS). Omalizumab and oral glucocorticoid therapy can play an important role in the treatment of RCRS, but there is still a lack of comparative studies on the efficacy and safety of the two. In addition, biomarkers are a hotspot in RCRS research, but there is still a lack of studies on changes in marker expression with disease progression and treatment.

In this study, patients aged 18-70 who were diagnosed with CRS were consecutively enrolled, and the patients were divided into RCRS and non-RCRS groups according to pathological results. The patients in the RCRS group were randomly divided (1:1:1) into the nasal spray hormone therapy group, the nasal spray hormone therapy + oral hormone therapy group, and the nasal spray hormone therapy + omalizumab therapy group by a multi-center, randomized, controlled study. The patients were treated for 6 months and followed up for 6 months after treatment. Clinical data such as symptom score and endoscopic score before and after treatment were collected, adverse events were recorded, and the differences in efficacy and safety among the groups were compared. Non-invasive samples such as nasal secretions and exfoliated cells were collected, and the expression and variation of different immune intrinsic markers were explored combined with follow-up results. The development of this project contributes to the establishment of a precise diagnosis and treatment system for refractory chronic sinusitis.


Eligibility criteria: Inclusion Criteria:

* (1) Age 18-70 years old;
* (2) All meet the diagnostic criteria of CRS in EPOS2020;
* (3) Patients with asthma were in a stable state, with FEV1 \> 80% of the predicted value or 80% of the optimal value of personal FEV1;
* (4) Good compliance, able to complete clinical observation. Meet the diagnostic criteria for RCRS that the number of eosinophils per high power field in the nasal mucosa is \>55 or the percentage of eosinophils in the tissue is ≥27%;
* (5) Investigator-assessed endoscopic bilateral Nasal Polyp Size Score (NPSS) of 4-6 (minimum score of 2 per nasal cavity);
* (6) Male or eligible female subjects (female subjects not pregnant or breastfeeding);
* (7) Ability to sign an informed consent form, including compliance with the requirements and restrictions outlined in the Informed Consent Form (ICF) and this protocol.

Exclusion Criteria:

* (1) Medication history of oral glucocorticoids within 3 months before enrollment, glucocorticoid atomization treatment and nasal hormone spray treatment within 2 weeks;
* (2) Oral glucocorticoid contraindications, such as diabetes, femoral head necrosis, gastric ulcer, etc.;
* (3) Any nasal and/or sinus surgery within 3 months before enrollment;
* (4) Patients have conditions or comorbidities that may preclude evaluation of the primary efficacy endpoint, such as: unilateral posterior nasal polyp of maxillary sinus, acute rhinitis, nasal infection or upper respiratory tract at the screening period or within 2 weeks before the screening period infection, acute asthma attack within 4 weeks, current drug-induced rhinitis, allergic fungal sinusitis (AFRS), benign or malignant tumor of nasal cavity, severe nasal septal deviation (Obstruction of one nostril, preventing full evaluation of nasal polyps in both nostrils), undergoing sinus or sinus surgery to alter the structure of the nasal wall resulting in an inability to evaluate the nasal polyp score, persistent drug-induced rhinitis (rebound or chemical-induced rhinitis);
* (5) Important clinical comorbidities that may interfere with clinical effectiveness, including but not limited to: active upper or lower respiratory tract infection, cystic fibrosis, eosinophilic granuloma with polyvasculitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, etc.;
* (6) Accompanying serious diseases or recurrent chronic diseases with poor systemic control, such as (but not limited to), active infection, cardiovascular disease, tuberculosis or other pathogen infection, diabetes, autoimmune disease, HIV, hepatitis B, Hepatitis C or parasitic diseases, malignant tumors, etc.;
* (7) Subjects with severe liver and kidney function injury; such as, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \>2 times the upper limit of normal, serum creatinine \> the upper limit of normal value; liver cirrhosis or currently unstable liver or biliary disease as assessed by the investigator;
* (8) Known or suspected immunosuppression, including a history of invasive opportunistic infections (such as tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pulmonary cysts, aspergillosis), even if the infection has subsided;
* (9) Suffering from known, pre-existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, renal, hepatic, hematological or other systemic abnormalities that have not been controlled by standard treatment;
* (10) Patient has been exposed to ionizing radiation above background 10mSv in the past 3 years due to occupational exposure or previous study participation (excluding clinically reasonable therapeutic or diagnostic exposure);
* (11) Women who were pregnant or planned to become pregnant during the study, or who were breastfeeding;
* (12) Subjects who were fertile but were reluctant to use medically approved and effective contraception;
* (13) Those with a history of alcohol or drug abuse;
* (14) Those who had been treated with monoclonal antibodies in the 6 months prior to enrollment;
* (15) Those who believed the patient had other medical or non-medical conditions that were not suitable for the study.

Primary outcomes:
measure: The change in endoscopic score
timeFrame: Baseline, week 2, week 4, week 8, week 12, week 14, week 16, week 20, week 24, month 9, month 12
Secondary outcomes:
measure: The change in nasal symptoms
timeFrame: Baseline, week 2, week 4, week 8, week 12, week 14, week 16, week 20, week 24, month 7, month 8, month 9, month 10, month 11,month 12
measure: The change in sinus CT score
timeFrame: Baseline, week 24
measure: The change in SNOT-22 score
timeFrame: Baseline, week 2, week 4, week 8, week 12, week 14, week 16, week 20, week 24, month 7, month 8, month 9, month 10, month 11,month 12
measure: The change in exfoliated cells and secretions
timeFrame: Baseline, week 2, week 4, week 8, week 12, week 14, week 16, week 20, week 24, month 9,month 12
measure: The change in asthma ACQ Score
timeFrame: Baseline, week 2, week 4, week 8, week 12, week 14, week 16, week 20, week 24, month7, month 8, month 9, month 10, month 11, month 12
measure: The change in AE / SA recording
timeFrame: Baseline, week 2, week 4, week 8, week 12, week 14, week 16, week 20, week 24, month7, month8, month 9, month 10, month 11, month 12
measure: The change in serum cortisol
timeFrame: Baseline, week 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tongren Hospital
state: Beijing
Study officials:
References: