VENTURI — Ventilation imaging comparing two triple-inhaler treatments for uncontrolled asthma

Open-label, Prospective, Crossover, Proof-of-concept Study to Evaluate the Effect of Triple Therapy With Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrrolate (BDP/FF/G) Via pMDI Compared With Non-extrafine Fluticasone Furoate/Umeclidinium/Vilanterol (FluF/UMEC/VI) Via DPI on Lung Ventilation and Clinical Outcomes in Subjects With Moderate to Severe Asthma

This trial tests two triple-combination inhalers to see which delivers medication better to the large and small airways in adults with uncontrolled asthma.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: University of Alabama at Birmingham (other)
• Locations: 1 site (Birmingham, Alabama)
• Trial ID: NCT07282886 on ClinicalTrials.gov

What this trial studies

Adults with uncontrolled asthma are randomized 1:1 to receive either beclometasone/formoterol/glycopyrronium (BDP/FF/G pMDI) twice daily or fluticasone furoate/umeclidinium/vilanterol (FluF/UMEC/VI DPI) once daily for 8 weeks, followed by a 4-week washout and crossover to the alternate inhaler for a second 8-week period. Spirometry, oscillometry, and ventilation imaging are performed at baseline and after each treatment period to compare large- and small-airway drug delivery. The randomized crossover design reduces between-subject variability and allows each participant to serve as their own control. Participants are trained in both pMDI and DPI technique and monitored for safety and exacerbations throughout the protocol.

Who should consider this trial

Good fit: Adults 18–75 years with a documented history of asthma who are symptomatic on ICS/LABA (ACT < 20) and have pre-bronchodilator FEV1 approximately 50–80% predicted and the ability to be trained on pMDI and DPI use are ideal candidates.

Not a fit: Patients with recent exacerbations requiring systemic steroids, those outside the lung-function or age criteria, those unable to use pMDI/DPI correctly, or those unable to attend the Birmingham site are unlikely to gain benefit from participation.

Why it matters

Potential benefit: If successful, the trial could identify which inhaler delivers medication more effectively to small airways and help guide inhaler choice to improve symptom control and lung function in uncontrolled asthma.

How similar studies have performed: Triple-combination inhalers such as Trelegy and Trimbow have shown clinical benefits in prior trials, but directly comparing regional drug delivery with ventilation imaging is a relatively novel approach.

Eligibility criteria

Inclusion Criteria:

* Subject's written informed consent obtained prior to any study-related procedure.
* Patients aged ≥ 18 and ≤ 75 years
* Confirmed diagnosis of asthma (patients must have a documented history of asthma for at least 1 year with diagnosis before the age of 40 and/or pre-bronchodilator FEV1 between 50-80% of their predicted normal value, after appropriate washout from bronchodilators)
* Symptomatic on ICS/LABA treatment with ACT \<20
* No exacerbations in the past 3 months requiring treatment with systemic corticosteroids or emergency department visit/ in-patient hospitalization
* The ability to be trained and correctly use a pressurized Meter Dose Inhaler (pMDI) and Dry Powder Inhaler (DPI)
* To have a cooperative attitude and the ability to perform the required outcomes measurements (e.g. spirometry maneuvers in sitting and supine position) and the ability to understand the risks involved
* WOCBP fulfilling one of the following criteria:

  1. WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signature of the informed consent and until the follow-up visit or
  2. WOCBP with physician confirmed non-fertile male partners (contraception is not required in this case).
* Female patients of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile, e.g. amenorrheic for ≥12 consecutive months without alternative medical cause). Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. If indicated, as per investigator's request, post-menopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges).

Exclusion Criteria:

* Pregnant or lactating female
* Patients who had an exacerbation, defined as a sustained and acute deterioration of subject's symptoms and signs (dyspnea, cough and/or sputum production/purulence) that was either moderate, i.e. require treatment with systemic (oral/IV/IM) corticosteroids and/or antibiotics, or severe, i.e. require hospitalization, if their associated treatment/hospitalization occurred within 3 months prior to V1
* Inability to carry out pulmonary lung function testing, to comply with study procedures or with study treatment intake
* History of near fatal asthma or of a past hospitalization for asthma in intensive care unit which, in the judgement of the Investigator, may have placed the patient at undue risk
* Patients using systemic corticosteroid medication in the 4 weeks or slow-release corticosteroids in the 12 weeks, prior to screening
* Patients who suffer from COPD as defined by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) document
* History of a diagnosis of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease which may have interfered with study evaluations
* Current smokers or current use of electronic cigarettes or ex-smokers with total cumulative exposure equal or more than 10 pack-years or having stopped smoking one year or less prior to screening visit
* Patients who had clinically significant cardiovascular condition according to investigator's judgement, such as but not limited to: congestive heart failure (NYHA class \>2), acute ischemic heart disease in the last year prior to study screening, history of sustained cardiac arrhythmias or sustained and non-sustained cardiac arrhythmias diagnosed in the last 6 months (sustained meant lasting more than 30 seconds or ending only with external action, or led to hemodynamic collapse; non-sustained meant \>3 beats \<30 seconds, and or ending spontaneously, and or asymptomatic), high degree impulse conduction blocks (\>2nd degree atrioventricular block type 2). Similarly, patients affected by persistent, long standing or paroxysmal AF were not considered for enrollment
* Patients who are unable to undergo imaging procedures for CT scans or MRI or demonstrate intolerance to Xenon gas
* Patients who have participated in a recent therapeutic trial (within past 6 months)
* Patients who have a milk protein allergy

Where this trial is running

Birmingham, Alabama

• The University of Alabama at Birmingham — Birmingham, Alabama, United States (RECRUITING)

Study contacts

• Study coordinator: Elizabeth Plan, RRT

Conditions: Asthma