Penicillium marneffei Infections and Infestations Human immunodeficiency virus (HIV) disease resulting in infectious and parasitic diseases
Conditions
Interventions
Current interventions as of 15/02/2012:
This study is a randomized, open-label, comparative, multi-center trial designed to assess the efficacy and safety of itraconazole versus amphot
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 15/02/2012 1. HIV positive AND 2. Age =18 years AND 3. Syndrome consistent with penicilliosis (primary or relapse) PLUS culture-confirmed diagnosis of penicilliosis (from blood, skin lesion scrapping, lymph node or bone marrow biopsy). Previous inclusion criteria 1. HIV positive 2. Age = 15 years 3. Male and female participants 4. Syndrome consistent with penicilliosis (fever, malaise, hepatosplenomegaly, lymphadenopathy, typical skin lesions) plus culture confirmed diagnosis of penicilliosis (from blood, skin lesion scrapping/biopsy, lymph node or bone marrow biopsy)
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 25/07/2013: 1. Age 48 hours Previous exclusion criteria (15/02/2012 to 25/07/2013): 1. Age 48 hours Original exclusion criteria (until 15/02/2012): 1. Age < 15 2. Pregnancy or urine ß-hCG positive 3. History of allergy or severe reaction to either itraconazole or amphotericin B 4. Unable to take oral medications 5. Documented treatment failure due to suspected drug resistance to either itraconazole or amphotericin B from another hospital or an outpatient clinic 6. Use of the following prohibited drugs: phenytoin, barbiturates, carbamazepine, rifampin, isoniazid, H2 blocker, HMG-CoA reductase inhibitors, cisapride, terfenadine, midazolam, dihydropyridine calcium channel blocker, cyclosporine, cyclophosphamide, tacrolimus, digoxin, coumadin, or investigational drugs. 7. Baseline aspartate transaminase (AST) or al
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome as of 15/02/2012: Absolute risk of death during the first 2 weeks after randomization Previous primary outcome: Mortality at 2 weeks of treatment (most deaths from penicilliosis occur in the acute phase of the disease and are reasonably assumed to have occurred by week 2 of presentation) | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcomes as of 25/07/2013: 1.Clinical endpoints 1.1 Overall survival until week 24 1.2 Time to treatment success (defined by absence of fungal growth in follow up culture, temperature <38ºC for 3 days, and complete resolution of lesions or lesions in the final stage of healing as judged by treating clinicians) 1.3 Relapse-free survival until week 24 of therapy (i.e., time from treatment success to the first treatment relapse or death). (Relapse is defined as recurrence of culture-confirmed penicilliosis after achieving treatment success at week 12) 1.4 Deaths from penicilliosis until week 24 (causes of death will be determined by investigators) 1.5 Time to change of therapy from assigned study therapy 1.6 Total number of patients with Grade 3 and Grade 4 AEs and SAEs, and the cumulative incidence of Grade 3 and Grade 4 AEs and SAEs, associated with cessation of randomly assigned therapy between treatment arms 1.7 Antifungal medication adherence 1.8 Incidence of Immune Reconstitution Diseases 2. Microbiological endpoints 2.1 Time to blood culture sterilization 2.2 Rate of early fungicidal activity as determined by serial blood samplings during therapy and measured by the decrease in log colony forming units per mL of blood (CFUs/mL) 2.3 Frequency and patterns of itraconazole and amphotericin B resistance emergence 3. Pharmacological endpoints 3.1 Antifungal concentration time curves 3.2 Maximum antifungal concentrations/MIC, area under the curve (AUC) of antifungals/MIC over time Previous secondary outcomes (15/02/2012 to 25/07/2013): 1.Clinical endpoints 1.1 Overall survival until week 24 1.2 Time to treatment success (defined by abs | — |
Countries
Viet Nam
Outcome results
None listed