Using the Blood Eosinophil Count to Guide Systemic Corticosteroid Treatment in Asthma Exacerbations

Investigating the Blood Eosinophil Count as a Biomarker to Guide Systemic Corticosteroid Treatment in Hospitalized Exacerbations of Asthma: a Randomized, Controlled, Open-label, Noninferiority Trial

Asthma attacks which are moderate-to-severe are typically treated with corticosteroids, but the optimal treatment duration is unknown and treatment responses can be variable. Inadequate treatment may compromise recovery, but increased exposure to corticosteroids is, in turn, associated with drug-related adverse effects.

There is a need for a biomarker to guide duration of corticosteroid treatment in asthma attacks. One such candidate biomarker is the blood eosinophil count, which may predict steroid-responsiveness. We hypothesize that the blood eosinophil count can potentially be used as a biomarker to guide the duration of corticosteroids in moderate-to-severe asthma attacks.

This study will recruit individuals hospitalized for asthma attack. Participants will be randomized to standard care or blood-eosinophil guided systemic corticosteroid therapy. Subjects in the standard arm will receive oral corticosteroids for a total of 5 days. Subjects in the blood-eosinophil guided arm will receive oral corticosteroids for a total of 5 days if admission eosinophil count is ≥ 0.300 x 10^3/µL, and receive 3 days of oral corticosteroids if the admission blood eosinophil is < 0.300 x 10^3/µL. The rate of treatment failure will be compared between these two groups.

Study Overview

• Status: Recruiting
• Conditions: Asthma; Asthma Attack
• Intervention / Treatment: Other: Standard care; Other: Eosinophil-directed care

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kaori Miranda; Phone Number: +65 8282 5761; Email: kaori_miranda@cgh.com.sg
• Study Contact Backup: Name: Siti Norashikin binte Fuad; Phone Number: +65 8044 1939; Email: siti_norashikin_fuad@cgh.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 168753
    • Recruiting
    • Singapore General Hospital
    • Contact: Mervyn Ong; Phone Number: +65 9188 4923; Email: mervyn.ong.h.p@sgh.com.sg
    • Principal Investigator: Mariko S Koh, MBBS
    • Sub-Investigator: Si Yuan Chew, MBBS
    • Sub-Investigator: Ken CH Lee, MBBS
    • Sub-Investigator: Pei yee Tiew, MBBS
  • Singapore, Singapore, 529889
    • Recruiting
    • Changi General Hospital
    • Contact: Kaori Miranda; Phone Number: +65 8282 5761; Email: kaori_miranda@cgh.com.sg
    • Contact: Siti Norashikin binte Fuad; Phone Number: +65 8044 1939; Email: siti_norashikin_fuad@cgh.com.sg
    • Principal Investigator: Anthony Yii, MB BChir
    • Sub-Investigator: Nicole Sieow, MBBS
    • Sub-Investigator: Tunn Ren Tay, MBBS
    • Sub-Investigator: Xue Ning Choo, MBBS
    • Sub-Investigator: Augustine Tee, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 21 years old
2. Admitted for acute exacerbation of asthma and have received ≤ 3 days of systemic corticosteroids
3. Have a had a blood eosinophil count (as part of routine clinical care) drawn before administration of systemic corticosteroid
4. Have not taken SCS within 7 days prior to presentation to hospital

Exclusion Criteria:

1. Concomitant pneumonia
2. Admission to high-dependency/intensive care unit, or requirement for invasive/noninvasive mechanical ventilation
3. Eosinophilia due to other known causes (eosinophilic granulomatosis and polyangiitis, parasitic infections, malignancy)
4. Other concomitant respiratory conditions e.g. chronic obstructive pulmonary disease, bronchiectasis
5. Those on anti-IL5 or anti-IL5R treatment
6. Pregnant subjects
7. Subjects who are already on an investigational drug or has been participating in another clinical study with an investigational product within the last 6 months
8. Subjects deemed by investigators to have a life expectancy of < 12 months (any cause)
9. Prisoners

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard care	Other: Standard care; Oral prednisolone for 5 days
Experimental: Eosinophil-directed care	Other: Eosinophil-directed care; Oral prednisolone for 5 days if eosinophil count is ≥ 0.300 x 10^3/µL, or 3 days if eosinophil is < 0.300 x 10^3/µL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants experiencing treatment failure	Defined as death from any cause, or need for invasive/noninvasive mechanical ventilation, or need to restart/extend systemic steroid treatment	Through the duration of the index admission for asthma attack, typically 3-5 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Length of hospital stay (number of days)	Through the duration of the index admission for asthma attack, typically 3-5 days
Cumulative steroid dose at index admission (mg prednisolone-equivalent)	Through the duration of the index admission for asthma attack, typically 3-5 days
Proportion of participants receiving additional systemic steroid course within 14 days	14 days
Asthma Control Questionnaire-5	At baseline, 7, 14, 30 and 90 days
Proportion of participants experiencing all-cause death	30 and 90 days
Proportion of participants who develop pneumonia	30 and 90 days
Proportion of participants who develop venous thromboembolism	30 and 90 days
Proportion of participants who develop sepsis	30 and 90 days
Proportion of participants who develop fractures	30 and 90 days
Proportion of participants who develop upper gastrointestinal bleeds/peptic or gastric ulcers	30 and 90 days
Time to next emergency department visit or admission for asthma	1 year

Collaborators and Investigators

• Sponsor: Changi General Hospital
• Collaborators: Singapore General Hospital
• Investigators: Principal Investigator: Anthony Yii, MB BChir, Changi General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2022
• Primary Completion (Anticipated): September 30, 2025
• Study Completion (Anticipated): September 30, 2026

Study Registration Dates

• First Submitted: May 29, 2022
• First Submitted That Met QC Criteria: June 9, 2022
• First Posted (Actual): June 14, 2022

Study Record Updates

• Last Update Posted (Actual): November 17, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: November 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
• Other Study ID Numbers: 03/FY2021/P2/10-A91

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