Introduction <p>Asthma imposes a high disease burden, with approximately half of patients experiencing uncontrolled disease despite inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) therapy. A previous randomised controlled trial demonstrated clinical benefits of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) single-inhaler triple therapy (SITT) versus FF/VI dual therapy in patients with moderate-severe asthma without a requirement for exacerbation history. Here, we present the protocol for the PERFORM pragmatic trial, comparing the effectiveness of initiating FF/UMEC/VI SITT via the ELLIPTA® inhaler (GSK) versus continuing or initiating non-ELLIPTA ICS/LABA usual care for a broad patient population with uncontrolled asthma.</p> Methods <p>PERFORM is a 52-week, stratified, randomised, open-label, active-controlled, parallel-group, global pragmatic trial enrolling adult patients with uncontrolled asthma, currently untreated or treated with ICS or ICS/LABA therapy. Patients will be randomised 1:1 to either initiate once-daily FF/UMEC/VI (intervention) or continue or initiate non-ELLIPTA ICS/LABA (control), receiving treatment in a usual care setting. The primary endpoint is the change from baseline in trough forced expiratory volume in 1&#xa0;s at week 24. The key secondary endpoint is whether patients achieve improvement (≥ 0.5-point decrease from baseline) in the Asthma Control Questionnaire-7 score at week 24. Other secondary endpoints include clinical remission, health-related quality of life, and work and activity impairment. The trial aims to randomise 1136 patients (568 per arm).</p> Planned Outcomes <p>PERFORM is a pragmatic randomised controlled trial generating data relevant to a broad population of patients with uncontrolled asthma representative of routine clinical practice. This trial will also include the first prospective data on clinical remission for patients treated with inhaled therapy.</p>