Safety and effects of oral ARV-1801 given in combination with intravenous ceftazidime or meropenem for treatment of melioidosis (a bacterial infection) in hospitalized patients

INTERVENTION: The study investigates the effect of 14 days of twice daily doses of oral tablet ARV‐1801 or oral tablet placebo in combination with IV meropenem or IV ceftazidime in patients hospitalized with melioidosis. Day 1 dosing will include two doses of 1500mg of ARV‐1801 or placebo administered 12 hours apart. Days 2‐14 will include 600 mg doses of ARV‐1801 or placebo administered every 12 hours. Patients must be on either IV ceftazidime or meropenem for the duration of study Days 1‐14. Randomization to active ARV‐1801 or placebo will be determined via IWRS in a 2:1 ratio. CONDITION: Treatment of melioidosis in hospitalized patients ; Infections and Infestations PRIMARY OUTCOME: All‐cause in‐hospital mortality in the modified intent‐to‐treat population (mITT) measured as reported by the sites using patient records at Day 14 SECONDARY OUTCOME: ; 1. All‐cause in‐hospital mortality in mITT population measured as reported by the sites using patient records on the last study day, expected to be on Day 28; 2. All‐cause in‐hospital mortality in the ITT population measured as reported by the sites using patient records at Day 14; 3. All‐cause in‐hospital mortality in the ITT population measured as reported by the sites using patient records on the last study day, expected to be on Day 28; 4. Clearance of positive baseline B. pseudomallei measured using blood cultures at Day 1, 3 and 7; 5. Number of days in the ICU in the mITT population measured as reported by the sites using patient records on the last study day, expected to be on Day 28; 6. Number of days on ventilator in the mITT population as reported by the sites using patient records on the last study day, expected to be on Day 28; 7. Length of hospital stay in the mITT population as reported by the sites using patient records on the last study day, expected to be on Day 28; 8. Seriousness of disease in mITT population as measured by the Melioidosis seriousness score at study baseline; INCLUSION CRITERIA: 1. Patient must provide written informed consent obtained prior to any study‐specific procedure being performed. 2. Patient must be at least 18 years of age or older at time of consent. 3. Patient must be hospitalized with suspected community‐acquired melioidosis, meeting at least one of the criteria below: 3.1 History of frequent contact with soil or surface water in an endemic area 3.2 Presence of a known underlying risk factor such as diabetes, renal insufficiency or renal stones, thalassemia 3.3 Special organ involvement such as splenic or hepatic abscess 3.4 An illness compatible with melioidosis, including the presence of sepsis, acute pneumonia, acute pyelonephritis, septic arthritis, parotid disease or skin or soft tissue infection 4. Patient must require intravenous antibiotics i.e., either ceftazidime or m