TREATment of Lower Respiratory Tract Infection in Selected Hospitals in Southern Sri Lanka (TREAT-SL): study protocol for a stepped-wedge, cluster-randomized clinical trial

Abstract Background Lower respiratory tract infection (LRTI) is a leading cause of hospitalization and antibacterial use globally. In low- and middle-income countries (LMICs), limited diagnostic resources contribute to inappropriate antibacterial use for LRTI. The aim of this trial is to determine the impact of an electronic clinical decision support tool (eCDST) on LRTI management in Southern Sri Lanka. Methods This is a prospective, open-label, stepped-wedge, cluster-randomized trial that will be conducted at three public hospitals. A total of 765 patients aged ≥ 14 years who are hospitalized with LRTI will be enrolled across 9 clusters; each cluster consists of a pair of wards (1 male and 1 female). The intervention consists of implementing an eCDST (RespiQuestAB) that physicians use on their mobile phones. RespiQuestAB integrates real-time influenza incidence in Sri Lanka with epidemiological and clinical predictors of LRTI etiology to estimate the probability of the following diagnoses: influenza, other viral (including SARS-CoV-2) infection, bacterial infection, noninfectious condition, or indeterminate. Point-of-care (POC) tests for influenza, SARS-CoV-2, Streptococcus pneumoniae, or procalcitonin are recommended if a positive result increases the probability of the associated diagnosis by at least 5%; clinicians may also order these tests independently. RespiQuestAB provides treatment recommendations regarding antibacterial and antiviral (oseltamivir) use based on the probability of diagnosis. Participants will be followed longitudinally to assess antibacterial prescription and clinical outcomes. The co-primary outcomes are as follows: (1) Duration of antibacterial prescription for the index visit and (2) a composite clinical outcome associated with worsening LRTI by day 30. Secondary outcomes include the individual clinical outcomes of the composite outcome, receipt, and duration of antibacterial and antiviral prescriptions and physician adherence to diagnostic tests and treatments recommended by RespiQuestAB. Exploratory outcomes include Desirability of Outcome Ranking (DOOR) level arranged in an ordinal scale, individual DOOR levels, and prescription of immunomodulatory therapy for SARS-CoV-2. Discussion Results of this clinical trial will provide information on the impact of the RespiQuestAB on antibacterial use and clinical outcomes among patients with LRTI in an LMIC setting. Trial registration ClinicalTrials.gov NCT06331364. Registered on March 25, 2024.