Inflammatory Indices in Predicting the Failure of Inhaled Corticosteroids Reduction in Young Participants With Asthma

NCT03788057 | Completed Results

• 1 other identifier: NITLD
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective, observational, interventional, single-blind study (blinded for a clinician in the field of inflammatory parameters). The aim of the study is evaluation of the usefulness of induced sputum eosinophilia and other inflammatory indices \[exhaled nitric oxide (NO), exhaled breath temperature, bronchial hyperresponsiveness\] in predicting the failure of treatment reduction with inhaled corticosteroids (ICS) in stable asthma in children and adolescents. In participants with a stable course of the asthma (confirmed in the run -in period), every 3 months the dose of ICS is halved (according to GINA guidelines) until the control is lost or the lowest daily ICS dose is reached (200 mcg, calculated as budesonide equivalent). Throughout the treatment reduction period, the participants run an observation card (clinical symptoms) and peak expiratory flow rate (PEFR) measurements. Clinical evaluation is performed every month, with spirometry, exhaled NO and exhaled breath temperature measurements. Before the reduction and then one month after the change of treatment, the hyperresponsiveness measurement is carried out with the sputum induction (combined method using hypertonic saline), and 2 months after the change of treatment with the exercise challenge test. In the case of loss of asthma control, beta-mimetic will be administered (temporarily) and return to dose of ICS before reduction or further increase of treatment is planned. In severe asthma exacerbations, oral steroids will be considered. The study is observational: treatment is modified according to GINA guidelines based on clinical data as part of routine medical care. Only difference compared do standard care is supplementary inflammation evaluation (exhaled NO, sputum eosinophilia, bronchial hyperreactivity).

Conditions

Asthma Chronic

Outcome Measures

Primary Outcomes (1)

• The Percentage of Patients With Loss of Asthma Control

  Criteria for loss of control (any of the following): * use of bronchodilators \> 5 times a week * the need for treatment with oral corticosteroids * PEFR decrease \>20% for 2 consecutive days, compared to the average run-in period

  at 9 months

Secondary Outcomes (1)

• Change in Sputum Eosinophilia

  at 1, 3, 4, 6 and 7 month

Other Outcomes (7)

• Change in Airway Hyperresponsiveness to Hypertonic Saline

  at 1, 3, 4, 6 and 7 month

• Change in Airway Hyperresponsiveness (Exercise)

  at 2, 5 and 8 month

• Change in Exhaled NO

  months 1 - 8

Study Arms (1)

stable asthma

OTHER

In patients with previously stable course of the asthma, every 3 months the symptoms are evaluated and the dose of ICS is customized - in accordance with the GINA guidelines. This decision is based solely on clinical data (control of symptoms) and is the same as in patients not participating in the study. In patients participating in the study, inflammatory parameters are also measured (sputum eosinophilia, eNO, EBT, bronchial reactivity), but results are not known to clinician taking decision about possible ICS dose reduction.

Other: ICS dose reduction

Interventions

ICS dose reduction OTHER

If control of symptoms is maintained (evaluation based on clinical symptoms solely), every 3 months the dose of ICS is halved according to GINA guidelines, until the control is lost or the lowest daily dose is reached (200 mcg, calculated as budesonide equivalent). In the case of loss of asthma control, beta-mimetic will be administered (temporarily) and return to the chronic administration of the previous, twice higher dose of ICS is restored (or further increase of treatment). In severe exacerbations, inclusion of oral steroids will be considered.

stable asthma

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• mild or moderate asthma with a stable course of at least 3 months:
• symptoms less than 4x per week,
• use of SABA below 3x a week,
• night awakening below 1x per week,
• FEV1\> 80% of predicted
• no dose change in ICS or use of systemic steroids from 3 months
• good adherence to treatment

You may not qualify if:

• infection or exacerbation of asthma requiring the use of systemic steroids (or changes in the dose of inhaled steroids) in the last 3 months before the study
• other chronic lung diseases or general diseases affecting the respiratory system
• tobacco smoking
• FEV1 below 80% of the predicted value

Sponsors & Collaborators

• National Institute for Tuberculosis and Lung Diseases, Poland: lead
• University of Rzeszow: collaborator
• The Regional Public Hospital in Lesko, Poland: collaborator

Study Sites (1)

The Regional Public Hospital in Lesko, Poland

Lesko, 38-600, Poland

Location

Related Publications (12)

• www.ginasthma.org

  RESULT

• Zacharasiewicz A, Wilson N, Lex C, Erin EM, Li AM, Hansel T, Khan M, Bush A. Clinical use of noninvasive measurements of airway inflammation in steroid reduction in children. Am J Respir Crit Care Med. 2005 May 15;171(10):1077-82. doi: 10.1164/rccm.200409-1242OC. Epub 2005 Feb 11.

  PMID: 15709050 RESULT

• Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, Wardlaw AJ, Pavord ID. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002 Nov 30;360(9347):1715-21. doi: 10.1016/S0140-6736(02)11679-5.

  PMID: 12480423 RESULT

• Fleming L, Wilson N, Regamey N, Bush A. Use of sputum eosinophil counts to guide management in children with severe asthma. Thorax. 2012 Mar;67(3):193-8. doi: 10.1136/thx.2010.156836. Epub 2011 Aug 8.

  PMID: 21825081 RESULT

• Jayaram L, Pizzichini MM, Cook RJ, Boulet LP, Lemiere C, Pizzichini E, Cartier A, Hussack P, Goldsmith CH, Laviolette M, Parameswaran K, Hargreave FE. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J. 2006 Mar;27(3):483-94. doi: 10.1183/09031936.06.00137704.

  PMID: 16507847 RESULT

• Li AM, Tsang TW, Lam HS, Sung RY, Chang AB. Predictors for failed dose reduction of inhaled corticosteroids in childhood asthma. Respirology. 2008 May;13(3):400-7. doi: 10.1111/j.1440-1843.2007.01222.x.

  PMID: 18399863 RESULT

• Prieto L, Bruno L, Gutierrez V, Uixera S, Perez-Frances C, Lanuza A, Ferrer A. Airway responsiveness to adenosine 5'-monophosphate and exhaled nitric oxide measurements: predictive value as markers for reducing the dose of inhaled corticosteroids in asthmatic subjects. Chest. 2003 Oct;124(4):1325-33. doi: 10.1378/chest.124.4.1325.

  PMID: 14555562 RESULT

• Deykin A, Lazarus SC, Fahy JV, Wechsler ME, Boushey HA, Chinchilli VM, Craig TJ, Dimango E, Kraft M, Leone F, Lemanske RF, Martin RJ, Pesola GR, Peters SP, Sorkness CA, Szefler SJ, Israel E; Asthma Clinical Research Network, National Heart, Lung, and Blood Institute/NIH. Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids. J Allergy Clin Immunol. 2005 Apr;115(4):720-7. doi: 10.1016/j.jaci.2004.12.1129.

  PMID: 15805990 RESULT

• Belda J, Parameswaran K, Lemiere C, Kamada D, O'Byrne PM, Hargreave FE. Predictors of loss of asthma control induced by corticosteroid withdrawal. Can Respir J. 2006 Apr;13(3):129-33. doi: 10.1155/2006/189127.

  PMID: 16642226 RESULT

• Jatakanon A, Lim S, Barnes PJ. Changes in sputum eosinophils predict loss of asthma control. Am J Respir Crit Care Med. 2000 Jan;161(1):64-72. doi: 10.1164/ajrccm.161.1.9809100.

  PMID: 10619799 RESULT

• Leuppi JD, Salome CM, Jenkins CR, Anderson SD, Xuan W, Marks GB, Koskela H, Brannan JD, Freed R, Andersson M, Chan HK, Woolcock AJ. Predictive markers of asthma exacerbation during stepwise dose reduction of inhaled corticosteroids. Am J Respir Crit Care Med. 2001 Feb;163(2):406-12. doi: 10.1164/ajrccm.163.2.9912091.

  PMID: 11179114 RESULT

• Cabral AL, Vollmer WM, Barbirotto RM, Martins MA. Exhaled nitric oxide as a predictor of exacerbation in children with moderate-to-severe asthma: a prospective, 5-month study. Ann Allergy Asthma Immunol. 2009 Sep;103(3):206-11. doi: 10.1016/S1081-1206(10)60183-4.

  PMID: 19788017 RESULT

Results Point of Contact

• Title: Dr. Janusz Ciółkowski
• Organization: The Regional Public Hospital in Lesko, Poland

ciolkowski.janusz@gmail.com

+48 134698071

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Clinician takes decision about possible change in treatment basing on clinical data only - is not aware of the results of the inflammatory parameters measurements
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A prospective, observational, interventional, single blind study. Clinician takes decision about possible reduction of ICS dose basing on clinical data only - is not aware of the results of the inflammatory parameters measurement.

Study Record Dates

• First Submitted: December 12, 2018
• First Posted: December 27, 2018
• Study Start: February 1, 2016
• Primary Completion: March 31, 2019
• Study Completion: March 31, 2019
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)