Treatment of melioidosis in hospitalized patients Infections and Infestations
Conditions
Interventions
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 melioi
Sponsors
Arrevus, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 meropenem for treatment of suspected melioidosis. 5. Patient must agree to stay in hospital for duration of ARV-1801 therapy, i.e., for at least 14 days. 6. Females of childbearing potential must use an acceptable method of birth control (surgically sterile, intrauterine device, vasectomized partner, oral contraceptive plus barrier contraceptive, hormone delivery system plus barrier contraceptive or condom in combination with contraceptive cream, jelly or foam) for the duration of the study drug administration phase and for 30 days thereafter.
Exclusion criteria
Exclusion criteria: 1. Patient is unable to tolerate oral therapy, either directly or via a nasogastric tube. 2. Patient has a known infection with an identified organism other than B. pseudomallei. 3. Patient is pregnant or lactating. 4. Patient has a known hypersensitivity to sodium fusidate, ceftazidime or meropenem. 5. Patient has been treated with intravenous antibiotics active against B. pseudomallei (including ceftazidime and meropenem) for longer than 48 hours prior to randomization. 6. Patient requires concomitant treatment with the following: 6.1 OATP1B1 and OATP1B3 substrates, in particular statins (e.g., HMG-CoA reductase inhibitors) 6.2 Medications metabolized by CYP2C8, such as glitazones (e.g., repaglinide) 6.3 CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital, and nafcillin) 7. Patient has had prior treatment with a CYP3A4 inducer, such as dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital, or nafcillin, within 7 days prior to enrollment. 8. Patient requires treatment with digoxin or warfarin unless a monitoring plan is in place to assess digoxin levels and/or prothrombin time as is relevant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Thailand
Contacts
Public ContactChristina Lockhart
Outcome results
None listed