Improving the Quality of Care for Asthma Patients at Risk of Exacerbations

NCT06596512 | Not Yet Recruiting

• 1 other identifier: 2024P001955
• Study Type: interventional
• Target: 4,100
• Locations: 1 country
• Sites: 6

Brief Summary

The goal of this trial test two known effective asthma strategies. Treatment guidelines recommend combination therapy of inhaled corticosteroids (ICS) with a long-acting beta-agonist (LABA) inhaled medications. This strategy is known as MART (maintenance and reliever therapy). The second strategy is PARTICS (patient activated reliever triggered ICS) strategy instructs patients to use an ICS metered dose inhaler (ICS) each time they use their rescue inhaler. In addition, they are instructed to take 5 puffs of the ICS after each rescue nebulizer use. PARTICS has been shown to reduce exacerbations, increase asthma control and quality of life, however, the question remains if PARTICS is as effective as MART and therefore be an alternative to MART. This trial will test PARTICS and MART head-to-head. The trial will include adults with moderate-to-severe asthma at risk for an asthma exacerbation, currently using a combination ICS. The main questions aim to answer:

• Is PARTICS as effective as SMART?
• Might PARTICS be more effective than SMART? Is the relative effectiveness of PARTICS versus SMART affected by frequent nebulizer use for asthma relief?
• Do PARTICS and SMART diverge in terms of their effectiveness on differing asthma outcomes important to patients?
• Do socioeconomic factors affect the relative effectiveness of PARTICS and SMART? Researchers will compare non frequent nebulizer (NFN) users - less than once a week to frequent nebulizer users - once a week or more, to assess whether the PARTICS strategy is ono-inferior (or superior to the MART strategy in reducing exacerbations, (primary outcome), increasing asthma control and quality of life and decrease days lost from work/school or usual activities. Most participants will be consented, enrolled, and randomized virtually, others will be consented, enrolled and randomized in person. Once randomized they will be instructed on how to use the prescribed medication:
• Participants randomized to MART will be instructed to use the prescribed ICS/LABA for maintenance and as needed for rescue.
• Participants randomized to PARTICS will be instructed to use the prescribed ICS each time they use their rescue inhaler and take 5 puffs of the newly prescribed ICS after each rescue nebulizer use.
• Participants will be followed for 16 months by monthly survey.

Conditions

Asthma; Asthma Chronic; Asthma Severe Persistent With Exacerbation; Asthma Moderate Persistent With Exacerbation

Keywords

ICS reliever therapy; Decrease exacerbations; iCARE

Outcome Measures

Primary Outcomes (1)

• Exacerbations

  The primary outcome is annualized rate of asthma exacerbations, defined as 72 hours of parenteral or oral corticosteroids to treat asthma symptoms or an asthma related-hospitalization. Participants are asked on their monthly surveys if they have had an exacerbation requiring at least 3 days of oral steroids or a hospitalization. If the participant answers yes to these questions, the clinical coordinating center contacts the site study coordinator to confirm an exacerbation in the patients EHR. If there is no record of an exacerbation in the EHR, the CCC contacts the patient for details. The information is entered into an exacerbation database and is reviewed separately by two investigators. If they are in agreement, the outcome is recorded (exacerbation yes or exacerbation no). If they do not agree or are unable to definitively determine if the patient had an exacerbation or not, the information goes to the adjudication committee of 3 for determination.

  Exacerbation information will be collected via monthly survey for 16 months.

Secondary Outcomes (3)

• Asthma Control over time

  Monthly for 16 months

• Asthma Symptom Utility Index (ASUI), Preference based quality of life

  Monthly for 16 months

• Days Lost Per Year From School/Work or Usual Activities

  Monthly for 16 months

Study Arms (4)

PARTICS - Non Frequent Nebulizer Users

ACTIVE COMPARATOR

Participants who use a nebulizer less than once a week are Non Frequent Nebulizer (NFN) Users. Adding the PARTICS strategy - Patient Activated Reliever-Triggered Inhaled CorticoSteroid (PARTICS). Patient will use inhaled corticosteroid at time of reliever inhaler or after reliever nebulizer use.

Drug: PARTICS using a single ICS add on

PARTICS - Frequent Nebulizer User

ACTIVE COMPARATOR

Participants who use a nebulizer once a week or more are "Frequent Nebulizer Users". Addition of the PARTICS strategy - Patient Activated Reliever-Triggered Inhaled CorticoSteroid (PARTICS). Patient will use inhaled corticosteroid at time of rescue inhaler or rescue nebulizer use

Drug: PARTICS using a single ICS add on

MART (non frequent nebulizer users) - MART strategy - Maintenance and Reliever Therapy

ACTIVE COMPARATOR

Participants who use a nebulizer less than once a week are Non Frequent Nebulizer (NFN) Users. MART strategy is a ICS/LABA combination therapy for maintenance and relief.

Drug: MART

MART (frequent nebulizer users)

ACTIVE COMPARATOR

Participants who use a nebulizer once a week or more are Frequent Nebulizer Users. MART strategy is a ICS/LABA combination therapy for maintenance and relief.

Drug: MART

Interventions

PARTICS using a single ICS add on DRUG

Participants randomized to PARTICS who use a nebulizer less than once a week are instructed to use the study prescribed ICS each time they use their rescue inhaler and take 5 puffs of the newly prescribed ICS after each rescue nebulizer use.

Also known as: Patient Activated Reliever Triggered ICS

PARTICS - Frequent Nebulizer User; PARTICS - Non Frequent Nebulizer Users

MART DRUG

Participants are instructed to use prescribed study ICS/LABA for maintenance and as needed for rescue.

MART (frequent nebulizer users); MART (non frequent nebulizer users) - MART strategy - Maintenance and Reliever Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinician diagnosis of asthma for ≥1 year;
• Age at enrollment--18-75 years old inclusive;
• One or more AEXs that occurred \< 12 months prior to enrollment. An AEX is defined as an asthma deterioration that either requires 72 hours or more of an oral or parenteral steroids OR a hospital stay for more than 24 hours for asthma. In the case of patients on biologics for asthma, the exacerbation must have also occurred after at least 6 months of biologic therapy;
• Currently prescribed an ICS/LABA containing preparation containing at least the lowest dose of ICS described in Table 2 as regular daily maintenance therapy for at least one month;
• Has a rescue SABA containing inhaler that they have used on average at least once a month.
• Able to provide consent in English for the feasibility study or in English or Spanish for the full study.

You may not qualify if:

• Life expectancy \<2 years;
• COPD diagnosis unless: a) they were a never smoker; OR b) former smoker with normal pulmonary function tests (PFT; FEV1/FVC ratio of \>70%); OR c) current smoker with normal PFTs within 24 months of enrollment; OR d) current or former smoker with obstruction on PFTs (FEV1/FVC ratio of \<70% but who demonstrates BOTH \>12% acute bronchodilator reversibility AND a normal diffusing capacity both within 24 months of enrollment (criteria successfully used in PREPARE);
• Use of single inhaler product that contains an ICS, LAMA and LABA or one containing both LABA and LAMA within 1 month of enrollment;
• Use of current biologic for less than 6 months;
• Known allergy to any of the components of the intervention;
• Coexisting lung disease (e.g. Cystic Fibrosis, connective tissue disease (unless asthma preceded diagnosis of connective tissue disease by at least 2 years), prematurity-born at 32 weeks or sooner, organ transplantation, bronchiectasis, sarcoid, and obliterative bronchiolitis, among others)
• Has been in an asthma drug treatment trial in past 60 days or within 5 half-lives, whichever is longer, prior to study visit.
• Living in household with someone already enrolled in the study.
• Using daily or every other day oral corticosteroids for asthma or any other condition
• An AEX in the prior 4 weeks
• History of bronchial thermoplasty in prior 6 months
• Poorly or uncontrolled atrial fibrillation
• Not on stable asthma medications for at least 1 month prior to enrollment
• Using doses of ICS/LABA lower than the minimum below:
• Budesonide 320 ug,

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (6)

Yale University

New Haven, Connecticut, 06510, United States

Location

Brigham and Womens Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19122, United States

Location

University of Wisconsin Madison

Madison, Wisconsin, 53792, United States

Location

Related Publications (6)

• Israel E, Cardet JC, Carroll JK, Fuhlbrigge AL, Pace WD, Maher NE, She L, Rockhold FW, Fagan M, Forth VE, Hernandez PA, Manning BK, Rodriguez-Louis J, Shields JB, Coyne-Beasley T, Kaplan BM, Rand CS, Morales-Cosme W, Wechsler ME, Wisnivesky JP, White M, Yawn BP, McKee MD, Busse PJ, Kaelber DC, Nazario S, Hernandez ML, Apter AJ, Chang KL, Pinto-Plata V, Stranges PM, Hurley LP, Trevor J, Casale TB, Chupp G, Riley IL, Shenoy K, Pasarica M, Calderon-Candelario RA, Tapp H, Baydur A. A randomized, open-label, pragmatic study to assess reliever-triggered inhaled corticosteroid in African American/Black and Hispanic/Latinx adults with asthma: Design and methods of the PREPARE trial. Contemp Clin Trials. 2021 Feb;101:106246. doi: 10.1016/j.cct.2020.106246. Epub 2020 Dec 11.

  PMID: 33316456 BACKGROUND

• Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC); Cloutier MM, Baptist AP, Blake KV, Brooks EG, Bryant-Stephens T, DiMango E, Dixon AE, Elward KS, Hartert T, Krishnan JA, Lemanske RF Jr, Ouellette DR, Pace WD, Schatz M, Skolnik NS, Stout JW, Teach SJ, Umscheid CA, Walsh CG. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-1270. doi: 10.1016/j.jaci.2020.10.003.

  PMID: 33280709 BACKGROUND

• Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, Cruz AA, Duijts L, Drazen JM, FitzGerald JM, Fleming LJ, Inoue H, Ko FW, Krishnan JA, Levy ML, Lin J, Mortimer K, Pitrez PM, Sheikh A, Yorgancioglu AA, Boulet LP. Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes. J Allergy Clin Immunol Pract. 2022 Jan;10(1S):S1-S18. doi: 10.1016/j.jaip.2021.10.001. Epub 2021 Oct 28.

  PMID: 34718211 BACKGROUND

• Imam SF, Zafar S, Oppenheimer JJ. Single maintenance and reliever therapy in treatment of asthma exacerbations. Ann Allergy Asthma Immunol. 2022 Dec;129(6):703-708. doi: 10.1016/j.anai.2022.07.024. Epub 2022 Jul 29.

  PMID: 35914659 BACKGROUND

• Sobieraj DM, Weeda ER, Nguyen E, Coleman CI, White CM, Lazarus SC, Blake KV, Lang JE, Baker WL. Association of Inhaled Corticosteroids and Long-Acting beta-Agonists as Controller and Quick Relief Therapy With Exacerbations and Symptom Control in Persistent Asthma: A Systematic Review and Meta-analysis. JAMA. 2018 Apr 10;319(14):1485-1496. doi: 10.1001/jama.2018.2769.

  PMID: 29554195 BACKGROUND

• Patel M, Pilcher J, Pritchard A, Perrin K, Travers J, Shaw D, Holt S, Harwood M, Black P, Weatherall M, Beasley R; SMART Study Group. Efficacy and safety of maintenance and reliever combination budesonide-formoterol inhaler in patients with asthma at risk of severe exacerbations: a randomised controlled trial. Lancet Respir Med. 2013 Mar;1(1):32-42. doi: 10.1016/S2213-2600(13)70007-9. Epub 2013 Mar 4.

  PMID: 24321802 BACKGROUND

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Central Study Contacts

Nancy Maher, MPH

CONTACT

781-879-0946; nmaher@mgb.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine Harvard Medical School Gloria M. and Anthony C. Simboli Distinguished Chair in Asthma Research Director of Clinical Research Pulmonary and Critical Care Division Allergy and Immunology Brigham & Women's Hospital

Study Record Dates

• First Submitted: September 11, 2024
• First Posted: September 19, 2024
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: March 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: The IPD will be available one year after the final research report is posted by our funder, PCORI which has not yet been determined.
• Access Criteria: As required by the funder, the data and supporting information will be submitted to the University of Michigan, hosts of the Inter-University Consortium for Pollical and Social Research. Researchers will submit a request to ICPSR and go through a vetting process for approval to receive the data and supporting documents.

Locations

US (6)