Periostin-guided Withdrawal of Inhaled Corticosteroids in Patients With Non-eosinophilic Asthma

Background: Asthma is a common chronic condition characterized by respiratory symptoms and hyperresponsive airways. According to treatment guidelines, patients with persistent asthma require daily treatment with inhaled corticosteroids (ICS). However, certain subgroups of asthma patients such as non-eosinophilic asthma patients do not respond well to the ICS treatment. In the present study, asthma patients treated with ICS and exhibiting low levels of eosinophilic biomarkers such as S-periostin, FeNO and blood eosinophils, are randomized 1:1 to either 1) tapering of ICS or 2) usual care. Thus, the aim of the present study is to investigate whether patients with non-eosinophilic asthma can sustain their level of disease control during ICS tapering.

Design: This is a randomized, controlled, one-center, non-inferiority study of ICS tapering in patients with non-eosinophilic asthma.

Inclusion and exclusion criteria: 1) Objectively secured asthma diagnosis, 2) Age 18-65 years, 3) ICS treatment equivalent to Budesonide 800 microg daily or more with at least 80% adherence, 4) Serum-periostin < 50 ng/ml, 5) FeNO<25 ppb at all prior visits, 6) Blood-eosinophils<0.15 at screening, 7) no allergic asthma history, 8) no daily smoking within 6 months, 9) no other respiratory disease, 10) no daily treatment with immunosuppressives, 11) no pregnancy, and 12) no history of drug or alcohol abuse.

Endpoints: Primary: Change in Control Questionnaire (ACQ) from baseline to post-tapered ICS and time from baseline to drop-out. Secondary: Change in FeNO, change in Serum-Periostin, change in FEV1, change in blood-eosinophils.

Methods: Relevant patients will be recruited from Respiratory Outpatient Wards. In total, 110 patients will be required. Visits will be performed at screening, at week 0, 4, 8, 12, 16, 26, 52. In the active arm, ICS dosage will be reduced to 50% at week 0 and removed at week 8. All visits include ACQ, FeNO, spirometry, blood eosinophils. S-periostin will be measured at screening and at week 8 and 16.

Study Overview

• Status: Recruiting
• Conditions: Asthma
• Intervention / Treatment: Drug: Tapering of inhaled corticosteroid (ICS) treatment

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Christiane Mosbech, MD; Phone Number: +4538621020; Email: christiane.mosbech@regionh.dk
• Study Contact Backup: Name: Charlotte Suppli Ulrik, Professor, MD, DMSc; Phone Number: +4538621020; Email: csulrik@dadlnet.dk

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Recruiting
    • Respiratory Research Unit, Copenhagen University Hospital Hvidovre
    • Contact: Christiane Mosbech, MD; Email: christiane.mosbech@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Astma patients followed in the Respiratory Outpatient Ward, Hvidovre Hospital, Amager Hospital or Glostrup Hospital.
• At least one of the following test suggestive for asthma, performed at any time during the outpatient course: 1) FEV1-reversibility on at least 12% and 200 ml after administration of bronchodilator or Prednisolon course, 2) positive bronchial provocation test, such as mannitol, 3) peakflow (PF)-variation of at least 20% assessed during a 14-day period, measured twice daily and at asthmatic symptoms, or 4) Variability in FEV1 on at least 12% and 200 ml
• Age 18-65 years
• Treated with ICS daily in doses equivalent to Budesonide 800 microg daily or more
• ICS adherence of at least 80% during the last year, assessed from used prescriptions
• Serum-periostin < 50 ng/ml at screening (8)
• FeNO < 25 ppb at all prior visits
• Blood-eosinophils <0,15 at screening
• Signed informed consent

Exclusion Criteria:

• History of allergic asthma
• Doctor-diagnosed pneumonia within 6 weeks prior to screening
• Daily smoking or former daily smoking within the last 6 months
• Known other respiratory conditions such as COPD or pulmonary sarcoidosis
• Known other chronic conditions that could impact or prevent study participation, including severe heart conditions and conditions requiring treatment with immunosuppressive drugs such as Prednisolon, Methotrexate or biological treatments, assessed by study doctor
• Pregnancy or planned pregnancy
• Abuse of alcohol or other recreational drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Group A; Usual care. Unchanged asthma medication during the entire study period.
Experimental: Group B; Tapering of ICS over 8 weeks. Dosis reduction of 50% in ICS treatment for 8 weeks, followed by total ICS removal. Other inhaled asthma medication remains unchanged during the entire study period.	Drug: Tapering of inhaled corticosteroid (ICS) treatment; Tapering of ICS treatment over 8 weeks. Follow-up over 52 weeks in total. Dosis reduction of 50% in ICS treatment for 8 weeks, followed by total ICS removal. Other inhaled asthma medication remains unchanged during the entire study period.; Other Names: budesonide; fluticasone proprionate; mometasone furoate; beclometasone dipropionate; ciclesonide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Control Questionnaire (ACQ) from baseline to post-tapered ICS	52 weeks
Time from baseline to drop-out	52 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in FeNO	52 weeks
Change in FEV1	52 weeks
Change in blood eosinophils	52 weeks
Change in serum periostin	52 weeks

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: May 3, 2017
• First Submitted That Met QC Criteria: May 3, 2017
• First Posted (Actual): May 5, 2017

Study Record Updates

• Last Update Posted (Actual): August 10, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2022

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; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Budesonide; Fluticasone; Ciclesonide; Beclomethasone; Mometasone Furoate
• Other Study ID Numbers: Asthmaperiostin

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
• product manufactured in and exported from the U.S.: No