The BLAAAST Trial: Bangladesh Lung Auscultation AI for Antibiotic Stewardship Randomized Controlled Trial

Participants will be screened for eligibility by study physicians. Children who screen positive will then be assessed for eligibility. Written informed consent will be obtained. All enrolled children will have a lung sound recording obtained. Study physicians will sequentially record lung sounds using the digital stethoscope from four chest positions (two anterior and two posterior) on participants. Each chest position recording is 15 seconds, and the overall procedure ~2 minutes. Lung sound recordings will be transferred to an encrypted tablet and analyzed by the convolutional neural network model to automatically detect normal and abnormal lung sounds. Blocked randomization will occur after the recording has been completed. Children who consent and meet eligibility criteria will be randomized into one of two arms.

Children randomized to the intervention will receive amoxicillin syrup (250mg/5ml concentration) or placebo based on the automated algorithm's lung sound classification. Children receiving a positive digital stethoscope result will receive amoxicillin while children receiving a negative digital stethoscope results will receive placebo. All children in the control arm (standard care) will receive amoxicillin. Treatment duration will be five days per Integrate Management of Childhood Illnesses (IMCI) guidelines, administering the study product twice daily. Children randomized to the control group will receive amoxicillin syrup (250mg/5ml concentration) for five days as all controls will meet IMCI pneumonia criteria. Study physicians and caregivers in the IMCI clinic will be masked to the randomization group. Masking will be achieved by applying the digital stethoscope to all enrolled children and concealing the automated algorithm result on the device.

Trained community healthcare worker paramedics equipped a pulse oximeter and paracetamol will conduct home visits for all participants on study days 2, 3, 5, and 14 after enrollment (defined as Day 1). A study physician will conduct the day 7 study visit and assign the primary outcome. A 24-hour window period will be permitted for each home visit in the event that the participant is not available on the scheduled visit day.

Any child that meets treatment failure criteria will be immediately transported to the study facility (Upazila Health Complex) for study physician confirmation and further treatment planning. Similarly, an oxygen saturation measured as 90-94% will prompt referral to the study physician for assessment for treatment failure. Study physician confirmation is required for a treatment failure outcome. Caregivers will be provided a trial telephone hotline for communications between scheduled visits (by text message or phone call), should parental concerns arise between household visits. If caregivers prefer, the caregiver may also return to the study clinic for a study physician reassessment between community health worker (CHW) household visits.

For any participant receiving amoxicillin or placebo who is confirmed to have a World Health Organization (WHO)-defined emergency sign, WHO-defined clinical danger sign, or WHO-defined hypoxemia, and the child will be hospitalized and receive parenteral antibiotics according to WHO-guidelines and aligned with Bangladesh national guidelines. Further treatment and clinical management will be at the discretion of the treating physician. For any participant on amoxicillin or placebo who is confirmed to have lower chest wall indrawing and/or very fast breathing for age on day 7 and who is confirmed to be without any WHO-defined emergency signs, to be without any WHO-defined clinical danger signs, and to be without WHO-defined hypoxemia, then the child will be initiated on oral amoxicillin-clavulanic acid over a minimum of 5 days. Further treatment and clinical management will be at the discretion of the treating physician. Unblinding will occur only when knowledge of treatment allocation is essential for the clinical management of a participant or when required to address a serious adverse event or unexpected problem posing risk to participant safety.