CST1-Guided Oral Glucocorticoids Management for CRSwNP (COMPASS)

Efficacy of CST1-Guided Oral Glucocorticoid Therapy for Chronic Rhinosinusitis With Polyps

Topical and systemic steroids constitute the first choice in medical treatment for nasal polyps. Glucocorticoids sensitivity is significantly correlated with CST1 in nasal secretions. The goal of this randomized, double-blind, placebo-controlled clinical trial is to clarify the efficacy of a short course of CST1-guided oral glucocorticoids therapy for chronic rhinosinusitis with nasal polyps. Subjects were randomized to receive either oral glucocorticoids or oral placebo for 2 weeks. Endoscopic polyp score, Total Nasal Symptom Score(TNSS), SNOT-22 score, Cystatin 1 and other biomarkers were evaluated before and after the treatment. Researchers will compare oral glucocorticoids group and oral placebo group to test CST1 predictive model of glucocorticoid therapy for Chronic Rhinosinusitis with Polyps.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Rhinosinusitis With Nasal Polyps; Glucocorticoids
• Intervention / Treatment: Drug: Oral Glucocorticoids; Drug: Oral placebo

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Beijing Tongren Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-70 years old；
2. All meet the diagnostic criteria of CRSwNP in EPOS2020;
3. Investigator-assessed endoscopic bilateral Nasal Polyp Size Score (NPSS) was greater than or equal to 4 (minimum score of 2 per nasal cavity);
4. Patients with asthma were in a stable state, with FEV1 > 50% of the predicted value or 50% of the optimal value of personal FEV1; (5) Good compliance, able to complete clinical observation.

Exclusion Criteria:

1. Medication history of oral glucocorticoids within 3 months before enrollment, antibiotics 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；
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;
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. Women who were pregnant or planned to become pregnant during the study, or who were breastfeeding;
10. Subjects who were fertile but were reluctant to use medically approved and effective contraception;
11. Those with a history of alcohol or drug abuse;
12. Those who believed the patient had other medical or non-medical conditions that were not suitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Glucocorticoids group; Intervention Period：oral glucocorticoids（methylprednisolone 24mg qd, 2-week duration）+nasal spray （Budesonide Nasal Spray 64ug per Nostril, bid, 2-week duration） follow-up period：nasal spray（Budesonide Nasal Spray 64ug per Nostril, bid, 24-week duration）	Drug: Oral Glucocorticoids; methylprednisolone 24mg qd, 2-week duration; Other Names: methylprednisolone
Placebo Comparator: Placebo group; Intervention Period：oral placebo+nasal spray（oral placebo 24mg qd, 2-week duration）+nasal spray （Budesonide Nasal Spray 64ug per Nostril, bid, 2-week duration） follow-up period：nasal spray（Budesonide Nasal Spray 64ug per Nostril, bid, 24-week duration）	Drug: Oral placebo; oral placebo 24mg qd, 2-week duration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in endoscopic polyp score	Bilateral polyp volume size described using the Nasal Polyp Size Score (NPSS) score. (0 - 4 points per side: 0 = no polyp; 1 = small polyp in the middle meatus, not reaching the inferior border of the middle turbinate; 2 = small polyp in the middle meatus, reaching the inferior border of the middle turbinate; 3 = large polyp protruding from the middle meatus, not reaching the inferior border of the inferior turbinate; 4 = large polyp that almost causes most or complete obstruction of the nasal cavity.)	Baseline, week 2, week 6, week 10, week 14, week 18, week 22, week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in Total Nasal Symptom Score（TNSS）	Total Nasal Symptom Score was are graded on a 3-point scale. (0= no symptoms; 1= mild symptoms; 2= moderate symptoms; 3= severe symptoms).	Baseline, week 2, week 6, week 10, week 14, week 18, week 22, week 26
The change in SNOT-22 score	The 22-item Sino-nasal outcome test (SNOT-22) was used to evaluate the changes in symptoms of patients. According to the severity of symptoms caused by RCRS, each item was divided into 6 levels: no distress (0 points), mild distress (1 point), mild distress (2 points) ), moderate distress (3 points), severe distress (4 points), very severe distress (5 points). The higher the score, the more severe the symptoms, and the final total score of the item is counted.	Baseline, week 2, week 6, week 10, week 14, week 18, week 22, week 26
The change in asthma ACQ Score	For patients with asthma, we assessed the change of asthma symptoms through the Asthma Control Questionnaire(ACQ). Each question was scored on a scale of 0 to 6 according to the severity. The result score of each item was averaged. A score of <0.75 indicated that the asthma had been completely controlled; a score of 0.75-1.5 indicates well-controlled asthma; a score of >1.5 indicates that asthma is not controlled.	Baseline, week 2, week 6, week 10, week 14, week 18, week 22, week 26
The change of CST1	The change of Cystatin 1	Baseline, week 2, week 6, week 10, week 14, week 18, week 22, week 26
The change of biomarker	Changes in expression levels of biomarker in nasal brush exfoliated cells, nasal secretions and nasal microbes.	Baseline, week 2, week 6, week 10, week 14, week 18, week 22, week 26
The change in AE / SAE recording	Any adverse event	Baseline, week 2, week 6, week 10, week 14, week 18, week 22, week 26
The needs of upgrading treatment	The needs of upgrading treatment includes surgery, oral glucocorticoids or monoclonal antibodies treatment.	Baseline, week 2, week 6, week 10, week 14, week 18, week 22, week 26
The change of inflammatory cell	The change of inflammatory cell in nasal polyps	Baseline, week 2, week 26

Collaborators and Investigators

• Sponsor: Beijing Tongren Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): October 17, 2022
• Primary Completion (Anticipated): December 30, 2024
• Study Completion (Anticipated): November 1, 2025

Study Registration Dates

• First Submitted: October 25, 2022
• First Submitted That Met QC Criteria: October 25, 2022
• First Posted (Actual): October 28, 2022

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Nose Diseases; Nasal Polyps; Polyps; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antiemetics; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Methylprednisolone; Glucocorticoids
• Other Study ID Numbers: TR-COMPASS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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