Voriconazole For Chronic Bronchopulmonary Aspergillosis

Study Overview
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Brief Summary
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To evaluate the efficacy of voriconazole (VFend(R)) as first line treatment for proven chronic bronchopulmonary aspergillosis, in minimally immunocompromised or non-immunocompromised patients after 6 months of treatment i.e. chronic necrotizing pulmonary

Official Title
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Voriconazole For Primary Therapy Of Proven, Chronic Bronchopulmonary Aspergillosis, In Minimally Immunocompromised Or, Non-Immunocompromised Hosts

Conditions
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Aspergillosis

Intervention / Treatment
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* Drug: Voriconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a chronic bronchopulmonary aspergillosis assessed by a compatible chest imagery (CT scan) and/or an endoscopic lesion sourced by photo, would it be: Complex aspergilloma non primarily operable, Chronic necrotizing pulmonary aspergillosis, Tracheo-bronchial aspergillosis, obstructive or necrotizing/pseudo-membranous. Exclusion Criteria: Patient with risk factor(s) of cardiac arrhythmia, symptomatic arrhythmia, treated by medication known to prolong QT interval, or prolongation of QTc interval > 450 msec in men and > 470 msec in women. Simple aspergilloma with primary indication of surgical treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Voriconazole<br>* Voriconazole oral : loading dose on day 1 : 400mg/12 hours; maintenance dose 200 mg /12 hours for 6 to 12 months depending on clinical response. Alternatively, patients may start on Voriconazole, IV, for 7 days loading dose, 6mg/Kg/12 hours on day one and maintenance dose 4 mg/Kg/12 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Successful Global Outcome at 6 Months: Chronic Bronchopulmonary Aspergillosis | Successful global outcome: composite assessment of radiological and mycological responses; defined as complete or partial radiological response and mycological eradication (absence of aspergillus); no success=criteria not met. Assessment was determined by the Data Review Committee (DRC). Complete response: resolution of radiographic and or bronchoscopic abnormalities attributable to aspergillosis present at baseline; partial response: reduction in diameter ≥ 50 percent on chest tomodensitometry (TDM) or regressed lesion on endoscopy witnessed by 2 different operators without any new lesion. | at 6 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Successful Global Outcome at Month 3 and End of Treatment: Chronic Bronchopulmonary Aspergillosis | Successful global outcome: composite assessment of radiological and mycological responses; defined as complete (resolution of radiographic and or bronchoscopic abnormalities attributable to aspergillosis present at baseline) or partial (reduction in diameter ≥ 50 percent on chest TDM or regressed lesion on endoscopy witnessed by 2 different operators without any new lesion) radiological response and mycological eradication after 3 months of treatment and after 9 or 12 months (in case of extension of treatment period beyond 6 months); no success=criteria not met. Assessment determined by DRC. | Month 3 and End of Treatment (Month 9 or Month 12) | 
| Number of Subjects With Successful Global Outcome at 6 Months: Chronic Necrotizing Pulmonary Aspergillosis (CNPA) and Tracheo-bronchial Aspergillosis | Successful global outcome: composite assessment of radiological and mycological responses; defined as complete or partial radiological response and mycological eradication (absence of aspergillus); no success=criteria not met. Assessment was determined by the Data Review Committee (DRC). Complete response: resolution of all radiographic and or bronchoscopic abnormalities attributable to the aspergillosis present at baseline; partial response: reduction in diameter ≥ 50% on chest tomodensitometry (TDM) or regressed lesion on endoscopy witnessed by 2 different operators without any new lesion. | at 6 months of treatment | 
| Number of Subjects With Successful Global Outcome at 6 Months: Complex Aspergilloma | Successful global outcome: composite assessment of radiological and mycological responses; defined as complete or partial radiological response and mycological eradication (absence of aspergillus); no success=criteria not met. Assessment was determined by the Data Review Committee (DRC). Complete response: resolution of all radiographic and or bronchoscopic abnormalities attributable to the aspergillosis present at baseline; partial response: reduction in diameter ≥ 50% on chest tomodensitometry (TDM) or regressed lesion on endoscopy witnessed by 2 different operators without any new lesion. | at 6 months of treatment | 
| Change From Baseline in Respiratory Clinical Signs and Symptoms on Visual Analog Scales (VAS) | Subject assessment of improvement of respiratory clinical signs and symptoms as indicated by the subject placing a mark on a 10 cm VAS scored 0 (better state of health) to 100 (poor state of health) for cough, dyspnea, sputum, hemoptysis, chest tightness, and nocturnal awakening. Change from baseline: mean of (value of scores on scale at treatment visit minus baseline value). | Baseline, Month 3, and Month 6, Month 9, or Month 12 [EOT], and End of study ([EOS] EOT + 6 months) | 
| Number of Subjects With Relapse | Relapse: any proven reappearance of pulmonary aspergillosis during the follow-up period, following a successful global outcome at EOT, and defined as a deterioration of clinical signs and symptoms, confirmed radiologically (chest [TDM] and or endoscopy) and mycologically (histology and or culture and or serology). | During the 6 months following EOT (EOT + 3 months, EOT + 6 months) | 
| Time to Relapse After EOT | Time (months) to relapse: any proven reappearance of pulmonary aspergillosis during the follow-up period, following a successful global outcome at EOT, and defined as a deterioration of clinical signs and symptoms, confirmed radiologically (chest [TDM] and or endoscopy) and mycologically (histology and or culture and or serology). | During the 6 months following EOT (EOT + 3 months, EOT + 6 months) | 
| Global Survival: Number of Subjects With an Outcome of Death | Number of subjects with an outcome of death (adverse event with a fatal outcome) through end of study. | Baseline through EOS (EOT + 6 months) | 
| Change From Baseline in Quality of Life (QOL): St. George's Hospital Respiratory Questionnaire | Subject administered questionnaire to measure improvement in QOL; 50 questions exploring 3 different areas: symptoms, impact on activity profile (activity), and impact on daily life (impacts). Each item in an area is weighted based on empirical data; scores range from lowest possible weight 0 to highest possible weight 100. Scores for each section and total score calculated using score calculation algorithms with higher scores indicating poor health. Change from baseline: mean of (value of scores on scale at treatment visit minus baseline value). | Baseline, Month 3, and Month 6, Month 9, or Month 12 [EOT], and EOS (EOT + 6 months) | 
| Number of Subjects With Complete or Partial Radiological Response | Radiological response: based on chest TDM except for tracheo-bronchialaspergillosis which was assessed by bronchoscopy. Complete response: resolution of all radiographic and or bronchoscopic abnormalities attributable to aspergillosis present at baseline; partial response: reduction in diameter ≥ 50% on chest TDM or regressed lesion on endoscopy witnessed by 2 different operators without any new lesion. | Month 3, and Month 6, Month 9, or Month 12 [EOT] | 
| Number of Subjects With Mycological Response of Eradication | Mycological response: eradication: absence of aspergillus species (spp) in bronchopulmonary samples: sputum, bronchial aspirate or bronchoalveolar lavage (BAL) (negative direct examination [exam] and negative culture), and negative histological exam when available; persistence (no eradication): presence of aspergillus spp in any relevant bronchopulmonary samples. Not done (presumed eradication): case reviewed by DRC for any mycological exams not performed to assess if case should constitute presumed eradication (no sputum due to clinical improvement). | Month 3, and Month 6, Month 9, or Month 12 [EOT] | 
| Number of Subjects With Complete or Partial Serological Response | Serological response: normalization (complete response) defined as return to normal values (≤ 1 arc); partial response defined as significant decrease but not complete (decrease of 2 or more arcs compared to baseline). Complete or partial response summarized as Improvement; based on arc values at visit compared to arc values at baseline (inclusion). | Month 3, and Month 6, Month 9, or Month 12 [EOT] |