CIVETTA: Correlating Inflammatory Values of FEno, SympToms, SpuTum and Lung Function in Asthma

Single-center, interventional, open-label, randomized phase II study aimed at describing the changes in airway inflammation at the onset of asthma symptoms that lead to the use of rapid acting bronchodilator (RABD) as a rescue medication in a mild to moderate asthma population. The study will assess whether there are differences in the airway inflammation profile in patients using a reliever medication containing ICS (anti-inflammatory rescue strategy) compared to a reliever medication containing only a bronchodilator for symptom relief (Non anti-inflammatory rescue strategy).

Study Overview

• Status: Active, not recruiting
• Conditions: Asthma
• Intervention / Treatment: Drug: Salbutamol; Drug: Fluticason either Beclometasone or Budesonide

Detailed Description

The study is structured into two distinct and separate phases, an observational and an interventional.

- Phase 1: Observational Phase The observational component of the study aims to describe the variations in airway inflammation at the onset of asthma symptoms when patients (n=50) are under the appropriate anti-asthma therapy (Standard Of Care, SOC), which includes a rapid-onset bronchodilator (RABD) as needed. The RABD used may be either salbutamol or formoterol, depending on the therapeutic strategy employed by the patient and the GINA Track followed.

Before and after taking the SOC rescue medication, the patient will measure markers of airway inflammation and clinical impact (FeNO, FEV1, PEF, VAS scale) using the "PEFESP kit" provided to each enrolled patient. They will record these values in the "patient diary" for the subsequent 48 hours.

- Phase 2: Interventional Phase In a crossover design according to the AB/BA scheme, it will be assessed whether there are differences in the airway inflammation profile in patients (n=30) using a reliever medication containing ICS compared to a reliever medication containing only a bronchodilator.

The interventional phase consists of two open-label monitoring phases, each lasting a maximum of 3 weeks, separated by a washout period of 3 to 7 days and for a maximum of 3 symptom episodes. As in the observational part, patients will be asked to record the markers of airway inflammation and the clinical impact of symptoms at the onset of the change from stable condition and in the 48 hours following the administration of the reliever medication.

Patient with mild asthma will be the first group of severity enrolled in the study.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Ferrara, Italy, 44121
    • Research Centre on Asthma and COPD, University of Ferrara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients already followed for asthma according to ERS/ATS criteria
• Mild and moderate asthma (GINA steps 1-3), with the exclusion of patients with severe asthma (GINA steps 4-5).

Exclusion Criteria:

Severe asthma (Gina steps 4 and 5)

• Inability to give informed consent
• Diagnosis of other clinically significant respiratory diseases
• Diagnosis of Chronic Obstructive Pulmonary Disease (COPD)
• History of smoking: > 10 pack/year or stop for less than 3 months
• Oral steroid therapy in the 2 months prior to enrollment
• Number of asthma exacerbations per year ≥ 2
• Pregnancy
• Evidence of clinically significant pathologies other than in respiratory system (i.e., cardiovascular, hepatic, renal, nervous, endocrinological, oncological, dermatological systems)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non ant-inflammatory rescue medication; Salbutamol 200 mcg pMDI x2	Drug: Salbutamol; One arm is a combination of salbutamol and fluticason as a rescue medication (anti-inflammatory rescue medication). The second arm is salbutamol only as a rescue medication (non-anti-inflammatory rescue medication).; Other Names: Salbutamol sulphate 200 mcg, pMDI
Experimental: Anti-inflammatory rescue medication; (Salbutamol 200 mcg + either Fluticason 250 mcg DPI or Beclometasone 400 mcg DPI or Budesonide 400 mcg pMDI ) x2	Drug: Fluticason either Beclometasone or Budesonide; One arm is a combination of salbutamol and an ICS as a rescue medication (anti-inflammatory rescue medication). The second arm is salbutamol only as a rescue medication (non-anti-inflammatory rescue medication).; Other Names: Fluticason Propionate 250 mcg DPI or Beclometasone dipropionate 400 mcg DPI or Budesonide 400 mcg pMDI or Budesonide 200 mcg DPI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate airway inflammation characteristics and changes at the onset of asthma symptoms requiring as-needed therapy (RABD) and the impact of inhaled steroid therapy in addition to RABD on airway inflammation	Inflammation will be assessed as FeNO levels after an anti inflammatory rescue medication compared to a non anti inflammatory rescue medication therapy repeatedly measured up to 48 hours at defined intervals	Patients are asked to perform repeated measurements of airway inflammation from the onset of symptoms to 48 hours after the administration of the rescue medication.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FEV1	The change in FEV after administration of an anti-inflammatory rescue medication and a non-anti-inflammatory rescue medication.	Patients are asked to perform repeated measurements of FEV1 from the onset of symptoms to 48 hours after the administration of the rescue medication.
change in Visual Analogue Scale (VAS) scale.	The change in VAS scale, used to measure the intensity of symptoms (0 lowest intensity, 10 highest intensity) after administration of an anti-inflammatory rescue medication and a non-anti-inflammatory rescue medication.	Patients are asked to perform repeated measurements of VAS scale from the onset of symptoms to 48 hours after the administration of the rescue medication.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in sputum eosinophils count	The change in sputum eosinophils count after administration of an anti-inflammatory rescue medication and a non-anti-inflammatory rescue medication.	Patients are asked to perform repeated sputum collections from the onset of symptoms until 48 hours after the administration of the rescue medication.

Collaborators and Investigators

• Sponsor: Università degli Studi di Ferrara
• Investigators: Principal Investigator: Alberto Papi, MD, Università degli Studi di Ferrara

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 29, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Budesonide; Fluticasone; Xhance; Albuterol; Beclomethasone
• Other Study ID Numbers: 4739 - 2022-002677-29

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