Itraconazole Versus Amphotericin B for the treatment of Penicilliosis (IVAP)

Not Applicable

Completed

• Conditions: Penicillium marneffei; Infections and Infestations; Human immunodeficiency virus (HIV) disease resulting in infectious and parasitic diseases

• Registration Number: ISRCTN97524945
• Lead Sponsor: niversity of Oxford (UK)

Brief Summary

1. 2017 results in https://www.nejm.org/doi/full/10.1056/NEJMoa1613306 (added 23/01/2019)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-12-19
• Study Completion: 2016-06-15
• Last Update Posted: 11 February 2019

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 440

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

Current exclusion criteria as of 25/07/2013:
1. Age <18
2. Pregnancy or urine ß-hCG positive
3. History of allergy or severe reaction to either itraconazole or amphotericin B
4. Central nervous system involvement (assessed clinically and by evidence of inflammation and/or infection in the CSF)
5. Use of the following prohibited drugs: phenytoin, barbiturates, carbamazepine, rifampin, HMG-CoA reductase inhibitors, cisapride, terfenadine, midazolam, dihydropyridine Ca channel blocker, cyclosporine, cyclophosphamide, tacrolimus, digoxin, quinidine, ergot derivatives, pimozide, coumadin, or investigational drugs.
6. Baseline AST or ALT =400 U/L
7. Absolute neutrophil count <500 cells/µL
8. Creatinine clearance of <30 by Cockcroft-Gault formula or on hemodialysis
9. Concurrent diagnosis of cryptococcal meningitis or active tuberculosis (as amphotericin B is the treatment of choice for cryptococcal meningitis, and tuberculosis treatment with INH and rifampin is contraindicated when used with itraconazole)
10. Current treatment with an antifungal drug for confirmed or suspected penicilliosis for >48 hours

Previous exclusion criteria (15/02/2012 to 25/07/2013):
1. Age <18
2. Pregnancy or urine ß-hCG positive
3. History of allergy or severe reaction to either itraconazole or amphotericin B
4. Central nervous system involvement (assessed clinically and by evidence of inflammation and/or infection in the CSF)
5. Use of the following prohibited drugs: phenytoin, barbiturates, carbamazepine, rifampin, isoniazid, H2 blocker, HMG-CoA reductase inhibitors, cisapride, terfenadine, midazolam, dihydropyridine Ca channel blocker, cyclosporine, cyclophosphamide, tacrolimus, digoxin, quinidine, ergot derivatives, pimozide, coumadin, or investigational drugs.
6. Baseline AST or ALT =10 times the upper limit of normal
7. Absolute neutrophil count < 500 cells/µL
8. Creatinine clearance of <10 by Cockcroft-Gault formula or on hemodialysis
9. Concurrent diagnosis of cryptococcal meningitis or active tuberculosis (as amphotericin B is the treatment of choice for cryptococcal meningitis, and tuberculosis treatment with INH and Rifampin is contraindicated when used with itraconazole)
10. Current treatment with an antifungal drug for confirmed or suspected penicilliosis for >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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Current primary outcome as of 15/02/2012:<br> Absolute risk of death during the first 2 weeks after randomization<br><br> Previous primary outcome:<br> 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)<br>