Voriconazole For Chronic Bronchopulmonary Aspergillosis

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Voriconazole

About this trial

This is an interventional treatment trial for Aspergillosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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).

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).

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).

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.

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).

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.

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).

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).

Full Information

NCT ID

NCT00159822

First Posted

September 8, 2005

Last Updated

January 13, 2010

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT00159822

Brief Title

Voriconazole For Chronic Bronchopulmonary Aspergillosis

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2010

Overall Recruitment Status

Completed

Study Start Date

July 2005 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

December 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Aspergillosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

1

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Voriconazole

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Subjects With Successful Global Outcome at 6 Months: Chronic Bronchopulmonary Aspergillosis

Description

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.

Time Frame

at 6 months of treatment

Secondary Outcome Measure Information:

Title

Number of Subjects With Successful Global Outcome at Month 3 and End of Treatment: Chronic Bronchopulmonary Aspergillosis

Description

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.

Time Frame

Month 3 and End of Treatment (Month 9 or Month 12)

Title

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

Description

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.

Time Frame

at 6 months of treatment

Title

Number of Subjects With Successful Global Outcome at 6 Months: Complex Aspergilloma

Description

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.

Time Frame

at 6 months of treatment

Title

Change From Baseline in Respiratory Clinical Signs and Symptoms on Visual Analog Scales (VAS)

Description

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).

Time Frame

Baseline, Month 3, and Month 6, Month 9, or Month 12 [EOT], and End of study ([EOS] EOT + 6 months)

Title

Number of Subjects With Relapse

Description

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 Frame

During the 6 months following EOT (EOT + 3 months, EOT + 6 months)

Title

Time to Relapse After EOT

Description

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).

Time Frame

During the 6 months following EOT (EOT + 3 months, EOT + 6 months)

Title

Global Survival: Number of Subjects With an Outcome of Death

Description

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

Time Frame

Baseline through EOS (EOT + 6 months)

Title

Change From Baseline in Quality of Life (QOL): St. George's Hospital Respiratory Questionnaire

Description

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).

Time Frame

Baseline, Month 3, and Month 6, Month 9, or Month 12 [EOT], and EOS (EOT + 6 months)

Title

Number of Subjects With Complete or Partial Radiological Response

Description

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.

Time Frame

Month 3, and Month 6, Month 9, or Month 12 [EOT]

Title

Number of Subjects With Mycological Response of Eradication

Description

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).

Time Frame

Month 3, and Month 6, Month 9, or Month 12 [EOT]

Title

Number of Subjects With Complete or Partial Serological Response

Description

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).

Time Frame

Month 3, and Month 6, Month 9, or Month 12 [EOT]

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

Pfizer Investigational Site

City

Nantes

State/Province

Cedex

ZIP/Postal Code

44093

Country

France

Facility Name

Pfizer Investigational Site

City

Angers Cedex

ZIP/Postal Code

49033

Country

France

Facility Name

Pfizer Investigational Site

City

Bobigny

ZIP/Postal Code

93000

Country

France

Facility Name

Pfizer Investigational Site

City

Brest Cedex

ZIP/Postal Code

29609

Country

France

Facility Name

Pfizer Investigational Site

City

Bris Sous Forges

ZIP/Postal Code

94640

Country

France

Facility Name

Pfizer Investigational Site

City

Caen Cedex

ZIP/Postal Code

14033

Country

France

Facility Name

Pfizer Investigational Site

City

Dinan Cedex

ZIP/Postal Code

22101

Country

France

Facility Name

Pfizer Investigational Site

City

Grenoble Cedex 09

ZIP/Postal Code

38043

Country

France

Facility Name

Pfizer Investigational Site

City

Lille Cedex

ZIP/Postal Code

59037

Country

France

Facility Name

Pfizer Investigational Site

City

Lyon Cedex

ZIP/Postal Code

69394

Country

France

Facility Name

Pfizer Investigational Site

City

Montpellier Cedex 5

ZIP/Postal Code

34295

Country

France

Facility Name

Pfizer Investigational Site

City

Paris Cedex 18

ZIP/Postal Code

75877

Country

France

Facility Name

Pfizer Investigational Site

City

Paris Cedex 20

ZIP/Postal Code

75970

Country

France

Facility Name

Pfizer Investigational Site

City

Paris

ZIP/Postal Code

75010

Country

France

Facility Name

Pfizer Investigational Site

City

Poitiers Cedex

ZIP/Postal Code

86021

Country

France

Facility Name

Pfizer Investigational Site

City

Reims Cedex

ZIP/Postal Code

51092

Country

France

Facility Name

Pfizer Investigational Site

City

Rouen Cedex

ZIP/Postal Code

76031

Country

France

Facility Name

Pfizer Investigational Site

City

Suresnes

ZIP/Postal Code

92150

Country

France

12. IPD Sharing Statement

Links:

URL

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A1501061&StudyName=Voriconazole%20and%20Bronchopulmonary%20Aspergillosis%20

Description

To obtain contact information for a study center near you, click here.

Aspergillosis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial