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Voriconazole For Chronic Bronchopulmonary Aspergillosis

Phase 2
Completed
Conditions
Aspergillosis
Interventions
Registration Number
NCT00159822
Lead Sponsor
Pfizer
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1Voriconazole-
Primary Outcome Measures
NameTimeMethod
Number of Subjects With Successful Global Outcome at 6 Months: Chronic Bronchopulmonary Aspergillosisat 6 months of treatment

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.

Secondary Outcome Measures
NameTimeMethod
Number of Subjects With Successful Global Outcome at Month 3 and End of Treatment: Chronic Bronchopulmonary AspergillosisMonth 3 and End of Treatment (Month 9 or Month 12)

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.

Number of Subjects With Successful Global Outcome at 6 Months: Chronic Necrotizing Pulmonary Aspergillosis (CNPA) and Tracheo-bronchial Aspergillosisat 6 months of treatment

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.

Number of Subjects With Successful Global Outcome at 6 Months: Complex Aspergillomaat 6 months of treatment

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.

Change From Baseline in Respiratory Clinical Signs and Symptoms on Visual Analog Scales (VAS)Baseline, Month 3, and Month 6, Month 9, or Month 12 [EOT], and End of study ([EOS] EOT + 6 months)

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).

Number of Subjects With RelapseDuring the 6 months following EOT (EOT + 3 months, EOT + 6 months)

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).

Time to Relapse After EOTDuring the 6 months following EOT (EOT + 3 months, EOT + 6 months)

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).

Global Survival: Number of Subjects With an Outcome of DeathBaseline through EOS (EOT + 6 months)

Number of subjects with an outcome of death (adverse event with a fatal outcome) through end of study.

Change From Baseline in Quality of Life (QOL): St. George's Hospital Respiratory QuestionnaireBaseline, Month 3, and Month 6, Month 9, or Month 12 [EOT], and EOS (EOT + 6 months)

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).

Number of Subjects With Complete or Partial Radiological ResponseMonth 3, and Month 6, Month 9, or Month 12 [EOT]

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.

Number of Subjects With Mycological Response of EradicationMonth 3, and Month 6, Month 9, or Month 12 [EOT]

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).

Number of Subjects With Complete or Partial Serological ResponseMonth 3, and Month 6, Month 9, or Month 12 [EOT]

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).

Trial Locations

Locations (1)

Pfizer Investigational Site

🇫🇷

Suresnes, France

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