Low-dose computed tomography and rapid molecular sputum testing in adults with suspected non-ventilator-associated hospital-acquired pneumonia: the HAP-FAST pilot sequential multiple assignment randomised trial with embedded qualitative and costing studies

Background Non-ventilator-associated hospital-acquired pneumonia (nv-HAP) diagnosis is imprecise; chest x-rays (CXR) lack detail and sputum culture delays targeted prescribing. However, the evidence base to support diagnostic improvement is sparse. We assessed the feasibility of a trial of low-dose thoracic CT and rapid molecular testing of sputum. Methods HAP-FAST was a UK NIHR funded, open-label pilot sequential multiple assignment randomised trial with qualitative and costing substudies in four UK hospitals (ClinicalTrials.gov: NCT05483309 ). Using research without prior consent (RWPC) and site-stratified web-based randomisation, clinicians allocated adults with suspected nv-HAP (excluding pregnancy and palliation), before their second antibiotic dose, 1:1 to CT or CXR; participants subsequently treated for nv-HAP with sputum available underwent another 1:1 randomisation to BIOFIRE ® FILMARRAY ® Pneumonia plus Panel (FAPP) with standard microbiology or standard microbiology alone . Feasibility outcomes included recruitment, consent, intervention delivery and data completeness through 90 days. Adverse events were not systematically collected. Analyses were intention-to-treat and descriptive. Results Between June 2023 and March 2024, 220 adults were randomised at stage-1 (109 CT; 111 CXR), reaching target three months early. Of 154/220 (70.0%) subsequently managed as nv-HAP, 92/154 (59.7%) could not produce sputum. 62/154 (40.3%; 28.2% of stage-1) were randomised to stage-2: 31 FAPP and 31 no-FAPP. Allocated imaging was recorded for 75/109 (68.8%) CT and 99/111 (89.2%) CXR participants; 6/31(19.4%) FAPP tests were not completed. Consent for follow-up was obtained for 142/220 (64.5%). Protocol-defined clinical cure was assessable in 1/220 participants. The day-90 resource-use questionnaire was returned by 55/110 participants (50.0%). Qualitative findings supported RWPC but identified needs for staged communication, lower-burden follow-up and improved diagnostic pathways. Excess bed days and readmissions drove costs but data capture requires refinement. Conclusions A definitive trial is plausible only with enhanced RWPC, diagnostic delivery and follow-up pathways, improved sputum procedures, stewardship-aligned outcomes and routine economic data capture.