Clinical trial NCT06596512: Improving the Quality of Care for Asthma Patients at Risk of Exacerbations
Official title: Improving the Quality of Care for Asthma Patients at Risk of Exacerbations
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Moderate-to-Severe Asthma
Keywords: ICS reliever therapy, Decrease exacerbations, iCARE
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
First posted: 2024-09-19
Enrollment: 4100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Asthma affects 25 million people in the USA with a disproportionate effect on African American/Black (AA/B) and Hispanic/Latinx (H/L) patients. Inhaled corticosteroids are the backbone of asthma therapy. A so-called SMART (Single Maintenance And Reliever Therapy) approach to ICS therapy has been recommended by US and international guidelines for patients with moderate to severe asthma, because it has been shown in multiple studies to reduce asthma exacerbations. However, these studies have been explanatory, with narrow entry criteria, have only been performed ex- US (with a formulation not available in the US), and have not included significant numbers of AA/B and H/L patients.

Further, there are significant barriers to implementation which include those related to patient patterns of concomitant medication use and beliefs. In a PCORI-funded pragmatic study in 1200 AA/B and H/L patients with asthma, designed with patient partners, we studied an alternative approach we call PARTICS (Patient Activated Reliever Triggered ICS). We reported, in this study published in the New England Journal of Medicine in 2022, that we not only reduced asthma exacerbations, we also improved other outcomes important to patients including asthma control, quality of life and days lost from school, work or usual activities. Our patient advisors have published on their positive experience and other advisors have collaborated with us to publish 9 additional papers which include such topics as an exploration of how socioeconomic factors affect asthma outcomes and how to simply identify patients at risk for asthma exacerbations, among additional topics. Both SMART and PARTICS have advantages and drawbacks. As seen in letters of support from the heads of the US and international guidelines for asthma treatment committees, the lack of direct comparison between the two represents a major gap in knowledge required to formulate best-care practice recommendations.

Specifically, it is unclear as to what degree one approach can substitute for the other and whether they differentially affect distinct domains of asthma outcomes. In collaboration with our advisors, we therefore propose iCARE (Improving the Quality of Care for Asthma patients at Risk of Exacerbations), a large pragmatic study to directly compare SMART to PARTICS in diverse populations and across multiple domains. The study results, regardless of outcome, will help guide the approach to patient-centered asthma care.

Eligibility criteria: Inclusion Criteria:

* Clinician diagnosis of asthma for ≥1 year;
* Age at enrollment--18-75 years old inclusive;
* One or more AEXs that occurred \&lt; 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.

Exclusion Criteria:

* Life expectancy \&lt;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 \&gt;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 \&lt;70% but who demonstrates BOTH \&gt;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,
* Fluticasone Advair Diskus/ Wixela 200-250 ug Advair HFA 180-230ug Airduo 110-113 ug Breo 100 ug
* Mometasone 200 ug

Primary outcomes:
measure: Exacerbations
timeFrame: Exacerbation information will be collected via monthly survey for 16 months.
Secondary outcomes:
measure: Asthma Control over time
timeFrame: Monthly for 16 months
measure: Asthma Symptom Utility Index (ASUI), Preference based quality of life
timeFrame: Monthly for 16 months
measure: Days Lost Per Year From School/Work or Usual Activities
timeFrame: Monthly for 16 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin Madison
state: Wisconsin
Study officials:
References:
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citation: 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.
citation: 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.