Chronic pulmonary aspergillosis Respiratory
Conditions
Interventions
Posaconazole
Liposomal amphotericin B Ambisome
Sequential therapy liposomal amphotericin B followed by posaconazole
Sponsors
Advances Against Aspergillosis
Infectious Diseases Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Subjects must be =16 years of age, of either sex. 2. Subjects must be diagnosed with CPA according to current diagnostic criteria (Denning et al. 2018). That is, as illness for >3 months and all the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. 3. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study. 4. Female subjects of childbearing age must be using a medically accepted method of birth control (oral or injectable hormonal contraceptive [with barrier method], medically prescribed intrauterine device (IUD), double-barrier method [condom in combination with spermicide], or vasectomy of the partner) before beginning study-drug treatment and agree to continue its use during the study or be surgically sterilized (i.e., hysterectomy or tubal ligation), if assigned to either posaconazole arms. Female subjects of childbearing potential should be counseled in the appropriate use of birth control while in this study. Female subjects who are not currently sexually active must agree and consent to use one of the above-mentioned methods should they become sexually active while participating in the study. 5. Female subjects of childbearing potential must have a negative serum beta-hCG (human chorionic gonadotropin) pregnancy test at baseline.
Exclusion criteria
Exclusion criteria: 1. Subjects enrolled concurrently in another therapeutic clinical trial. 2. Female subjects who are pregnant, intend to become pregnant or are nursing. 3. Subjects who have used any phase 1 or phase 2 investigational drugs or biological agents within 30 days of study drug start. These patients can be enrolled after 30 days if no further experimental medicine administration is expected. 4. Subjects must be free of any immediately life-shortening systemic disease that would interfere with the study evaluations or preclude completion of 6 months participation, not including CPA or respiratory impairment. 5. Subjects cannot be part of the staff personal directly involved with this study or who are a family member of the investigational study staff. 6. Subjects having any history of clinically significant QTc prolongation (QTc>500 msec by Fridericia’s correction), torsade de pointes, or unstable proarrhythmic conditions, where the risk for administering azole therapy is unacceptable compared to the potential benefit. 7. Subjects who may require treatment with other medications that cannot be stopped and for which there is a known contraindication to co-administration of posaconazole or amphotericin B. 8. Patients taking ivabradine, phenytoin, carbamazepine, bedaquiline, quetiapine and continuous sildenafil will be excluded. 9. Patients taking rifampicin (rifampin), rifabutin, ranolazine, fentanyl, efavirenz, ritonavir, praziquantel, artemether/lumefantrine will be excluded, unless the interfering drug can be stopped, in which case they can be reconsidered for inclusion 20 days after discontinuation of the interfering agent. 10. Subjects with moderate or severe liver dysfunction defined as baseline elevation of transaminases [aspartate aminotransferase (AST) or alanine aminotransferase (ALT)] >5 times the upper limit of normal (ULN) OR a combination of elevated transaminases and bilirubin meeting Hy’s rule (ALT or AST > 3X ULN and total bilirubin > 2X ULN). 11. Subjects with electrolyte imbalances including hypo (5.0mmol/L), must have this corrected to the normal range before enrolment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment success will be evaluated using the following criteria: 1.?5% gain in body weight 2.?7-point fall from baseline in St. George’s Respiratory Questionnaire (SGRQ) Quality of Life scores 3.?25% decline in quantitative Aspergillus IgG titers 4.Stable or improved radiological parameters. The overall primary outcome will be assessed at 6 months using a 5-level ordinal scale, with levels ranging from zero (not meeting any of the response criteria above) to four (1 point for each response criterion met), with higher scores indicating improved outcome. | — |
Secondary
| Measure | Time frame |
|---|---|
| To measure emergence of isolates of Aspergillus with resistance/reduced susceptibility to posaconazole in both arms. ;12-month all-cause mortality in each arm;Remission rates;Relapse-free survival time;Treatment success using the 5-level ordinal score ;Proportions of patients in each arm developing clinical and DAIDS laboratory-defined grade III/IV adverse events;Body weight;Change from baseline in St. George’s Respiratory Questionnaire (SGRQ) Quality of Life (QoL) scores;Change in quantitative serum Aspergillus IgG titers;An exploratory endpoint using performance on the exercise oximetry step test. | — |
Countries
Uganda
Contacts
Public ContactDavid Denning
Professor of Infectious Diseases in Global Health
Outcome results
None listed