Clinical Outcomes with High-Dose Amoxycillin–Clavulanate Suspension in Children with Respiratory Tract Infections: A Prospective, Multicentre, Phase IV Study in India

INTRODUCTION: Respiratory tract infections (RTIs) are the leading causes of paediatric morbidity worldwide, particularly in regions with high antimicrobial resistance (AMR). High-dose amoxycillin-clavulanate formulations, which increase amoxycillin exposure while maintaining standard clavulanate levels, offer enhanced antibacterial coverage with acceptable tolerability. This phase IV study evaluated the safety and observed clinical outcomes of a high-dose oral suspension of amoxycillin (600 mg/5 mL) and potassium clavulanate (42.9 mg/5 mL) in Indian children with upper RTIs or non-severe lower RTIs. METHODS: This prospective, multicentre, open-label study enrolled children aged ≥ 3 months to < 18 years with tonsillopharyngitis, acute bacterial sinusitis, acute otitis media, or lobar and/or bronchopneumonia across 12 Indian centres. Participants received amoxycillin-clavulanate at 90/6.4 mg/kg/day in two divided doses for 5-10 days. The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs). Secondary endpoints included serious adverse events (SAEs), diarrhoea incidence, clinical cure, clinical improvement, clinical failure, clinical relapse and time to symptom resolution. Safety analyses used the safety population, while clinical outcomes were analysed using the modified intention-to-treat population. RESULTS: All 174 enrolled children completed the study. Overall, 21 patients (12.1%) experienced 23 TEAEs (all mild and self-limiting). No SAEs, discontinuations or clinically significant laboratory or vital sign changes were reported. Diarrhoea occurred in 6.3% of patients. Overall clinical cure rate was 82.8% (95% CI 76.3-88.1), highest in acute bacterial sinusitis (95.8%), tonsillopharyngitis (83.7%), acute otitis media (76.9%) and pneumonia (76.5%). An additional 17.2% demonstrated clinical improvement without the need for alternative therapy. No clinical failures or relapses were observed. Overall median time to symptom resolution was 6 days. CONCLUSION: High-dose amoxycillin-clavulanate demonstrated a favourable safety profile. Observed clinical outcomes were favourable, with a clinical cure or improvement rate of 100% across all patients. These findings provide post-marketing safety and tolerability data to support clinical decision-making in settings with rising AMR. TRIAL REGISTRATION: Prospectively registered on Clinical Trials Registry-India [CTRI/2023/08/056267] on 08th August 2023; URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODY5MzI=&Enc=&userName= .