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出境医 / 临床实验 / Six Months Versus 12 Months of Oral Itraconazole Therapy for Management of Treatment naïve Subjects With CPA

Six Months Versus 12 Months of Oral Itraconazole Therapy for Management of Treatment naïve Subjects With CPA

Study Description
Brief Summary:
The treatment options majorly consist of medical management with at least 6-month long treatment with antifungal drugs - most significantly the azole groups. Itraconazole is the preferred azole for the treatment of CPA. The duration of treatment with oral itraconazole remains uncertain. In a previous study the use of oral itraconazole for 6-months a favorable overall response was seen in 76% of the subjects. Moreover, about 30%-50% of the subjects have disease relapse that requires prolonged therapy. It is likely that a longer duration of itraconazole would have a higher response rate and thus, lower risk of relapse after discontinuation of therapy. In this randomized controlled trial, we compare the clinical outcomes of six months versus twelve months of itraconazole therapy in treatment naïve subjects with chronic pulmonary aspergillosis

Condition or disease Intervention/treatment Phase
Chronic Pulmonary Aspergillosis Drug: Itraconazole 400 mg Phase 3

Detailed Description:

Aspergillus is a saprophytic fungus which is present normally in our surroundings and causes a large number of pulmonary diseases spreading through inhalational route. The spectrum of disease caused by aspergillus spp. is wide with the manifestations of the disease being governed primarily by the status of the underlying host immunity, which then determines the nature of the host-aspergillus interaction. Patients with an intact immunity have a more stable and indolent form of disease like aspergilloma whereas with a worsening immune status, the risk of invasive disease increases. Chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA) are two of the commonest pulmonary manifestations seen in non-immunocompromised patients whereas invasive pulmonary aspergillosis being more common in the immunocompromised patients.

Estimates suggest that CPA affects around 3 million people across the globe, which may still be an under estimated number as the disease co exists with other pulmonary co-morbidities which make accurate diagnosis a pitfall. In India the annual incidence of CPA was estimated in 2011 and varied between 27,000-0.17 million cases, with different estimates. Based on the mortality rate for CPA which was estimated to be 15% annually, the 5-year prevalence of CPA was placed at 290,147 cases with 5-year prevalence rate being 24 per 100,000 in the same year. The disease confers significant morbidity and mortality, making it a significant burden for the society as well as the healthcare. Apart from the respiratory symptoms, CPA causes significant constitutional symptoms as well which adds to the misery of the patient. The diagnosis of CPA is based on presence of chronic symptoms, consistent radiology and demonstration of Aspergillus by direct (culture) or indirect (serological) methods. Even though CPA is more of a disease spectrum but overall it is characterized by slowly progressive lung cavitation which may or may not show presence of mycetoma /fungal ball in patients with pre-existing structural lung diseases, even though other patterns have also been identified.

The treatment options majorly consist of medical management with at least 6-month long treatment with antifungal drugs - most significantly the azole groups. Itraconazole is the preferred azole for the treatment of CPA. The duration of treatment with oral itraconazole remains uncertain. In a previous study the use of oral itraconazole for 6-months a favorable overall response was seen in 76% of the subjects. Moreover, about 30%-50% of the subjects have disease relapse that requires prolonged therapy. It is likely that a longer duration of itraconazole would have a higher response rate and thus, lower risk of relapse after discontinuation of therapy. In this randomized controlled trial, we compare the clinical outcomes of six months versus twelve months of itraconazole therapy in treatment naïve subjects with chronic pulmonary aspergillosis.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 288 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial to Compare the Clinical Outcomes of Six Months Versus 12 Months of Oral Itraconazole Therapy for Management of Treatment naïve Subjects With Chronic Pulmonary Aspergillosis
Actual Study Start Date : January 31, 2019
Actual Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2021
Arms and Interventions
Arm Intervention/treatment
Active Comparator: Six months
Six months of itraconazole
Drug: Itraconazole 400 mg
Duration of itraconazole
Other Name: sporanox

Experimental: 12 months
12-months of itraconazole
Drug: Itraconazole 400 mg
Duration of itraconazole
Other Name: sporanox

Outcome Measures
Primary Outcome Measures :
  1. Relapse rate [ Time Frame: 1 year after treatment completion ]
    number of relapses at 1 year after completion of therapy


Secondary Outcome Measures :
  1. Response [ Time Frame: at 6 to 12 months ]
    Proportion of subjects with an overall favourable response at the end of oral itraconazole therapy

  2. Adverse events [ Time Frame: 1 year ]
    adverse events due to itraconazole


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: includes presence of all the following:

  • one or more clinical symptoms (persistent cough, recurrent hemoptysis, weight loss, malaise, fever and dyspnea) for ≥3 months
  • slowly progressive or persistent radiological findings (one or more cavities and surrounding fibrosis, infiltrates, consolidation, with or without fungal ball or progressive pleural thickening) on computed tomography (CT) of the thorax
  • immunological (A.fumigatus-specific IgG >27 mgA/L or positive Aspergillus precipitins) or microbiological evidence of Aspergillus infection (growth of Aspergillus in respiratory secretions or serum galactomannan index >0.5 or BALF galactomannan index >1) and,
  • exclusion of other pulmonary disorders with similar presentation.

Exclusion Criteria:

  • failure to provide informed consent
  • patients on immunosuppressive drugs, intake of prednisolone (or equivalent) >10 mg for at least 3 weeks or a diagnosis of human immunodeficiency virus syndrome
  • intake antifungal azoles for >3 weeks in the preceding six months
  • subjects with active pulmonary infection due to mycobacterium tuberculosis or mycobacteria other than tuberculosis (MOTT)
  • subjects with others forms of pulmonary aspergillosis (allergic bronchopulmonary aspergillosis, chronic necrotizing aspergillosis and angio-invasive aspergillosis)
  • pregnancy
Contacts and Locations

Locations
Layout table for location information
India
Inderpaul Singh
Chandigarh, India, 160012
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Tracking Information
First Submitted Date  ICMJE April 9, 2019
First Posted Date  ICMJE April 19, 2019
Last Update Posted Date March 23, 2021
Actual Study Start Date  ICMJE January 31, 2019
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2019)
Relapse rate [ Time Frame: 1 year after treatment completion ]
number of relapses at 1 year after completion of therapy
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2019)
  • Response [ Time Frame: at 6 to 12 months ]
    Proportion of subjects with an overall favourable response at the end of oral itraconazole therapy
  • Adverse events [ Time Frame: 1 year ]
    adverse events due to itraconazole
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Six Months Versus 12 Months of Oral Itraconazole Therapy for Management of Treatment naïve Subjects With CPA
Official Title  ICMJE A Randomized Controlled Trial to Compare the Clinical Outcomes of Six Months Versus 12 Months of Oral Itraconazole Therapy for Management of Treatment naïve Subjects With Chronic Pulmonary Aspergillosis
Brief Summary The treatment options majorly consist of medical management with at least 6-month long treatment with antifungal drugs - most significantly the azole groups. Itraconazole is the preferred azole for the treatment of CPA. The duration of treatment with oral itraconazole remains uncertain. In a previous study the use of oral itraconazole for 6-months a favorable overall response was seen in 76% of the subjects. Moreover, about 30%-50% of the subjects have disease relapse that requires prolonged therapy. It is likely that a longer duration of itraconazole would have a higher response rate and thus, lower risk of relapse after discontinuation of therapy. In this randomized controlled trial, we compare the clinical outcomes of six months versus twelve months of itraconazole therapy in treatment naïve subjects with chronic pulmonary aspergillosis
Detailed Description

Aspergillus is a saprophytic fungus which is present normally in our surroundings and causes a large number of pulmonary diseases spreading through inhalational route. The spectrum of disease caused by aspergillus spp. is wide with the manifestations of the disease being governed primarily by the status of the underlying host immunity, which then determines the nature of the host-aspergillus interaction. Patients with an intact immunity have a more stable and indolent form of disease like aspergilloma whereas with a worsening immune status, the risk of invasive disease increases. Chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA) are two of the commonest pulmonary manifestations seen in non-immunocompromised patients whereas invasive pulmonary aspergillosis being more common in the immunocompromised patients.

Estimates suggest that CPA affects around 3 million people across the globe, which may still be an under estimated number as the disease co exists with other pulmonary co-morbidities which make accurate diagnosis a pitfall. In India the annual incidence of CPA was estimated in 2011 and varied between 27,000-0.17 million cases, with different estimates. Based on the mortality rate for CPA which was estimated to be 15% annually, the 5-year prevalence of CPA was placed at 290,147 cases with 5-year prevalence rate being 24 per 100,000 in the same year. The disease confers significant morbidity and mortality, making it a significant burden for the society as well as the healthcare. Apart from the respiratory symptoms, CPA causes significant constitutional symptoms as well which adds to the misery of the patient. The diagnosis of CPA is based on presence of chronic symptoms, consistent radiology and demonstration of Aspergillus by direct (culture) or indirect (serological) methods. Even though CPA is more of a disease spectrum but overall it is characterized by slowly progressive lung cavitation which may or may not show presence of mycetoma /fungal ball in patients with pre-existing structural lung diseases, even though other patterns have also been identified.

The treatment options majorly consist of medical management with at least 6-month long treatment with antifungal drugs - most significantly the azole groups. Itraconazole is the preferred azole for the treatment of CPA. The duration of treatment with oral itraconazole remains uncertain. In a previous study the use of oral itraconazole for 6-months a favorable overall response was seen in 76% of the subjects. Moreover, about 30%-50% of the subjects have disease relapse that requires prolonged therapy. It is likely that a longer duration of itraconazole would have a higher response rate and thus, lower risk of relapse after discontinuation of therapy. In this randomized controlled trial, we compare the clinical outcomes of six months versus twelve months of itraconazole therapy in treatment naïve subjects with chronic pulmonary aspergillosis.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Pulmonary Aspergillosis
Intervention  ICMJE Drug: Itraconazole 400 mg
Duration of itraconazole
Other Name: sporanox
Study Arms  ICMJE
  • Active Comparator: Six months
    Six months of itraconazole
    Intervention: Drug: Itraconazole 400 mg
  • Experimental: 12 months
    12-months of itraconazole
    Intervention: Drug: Itraconazole 400 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 17, 2019)
288
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria: includes presence of all the following:

  • one or more clinical symptoms (persistent cough, recurrent hemoptysis, weight loss, malaise, fever and dyspnea) for ≥3 months
  • slowly progressive or persistent radiological findings (one or more cavities and surrounding fibrosis, infiltrates, consolidation, with or without fungal ball or progressive pleural thickening) on computed tomography (CT) of the thorax
  • immunological (A.fumigatus-specific IgG >27 mgA/L or positive Aspergillus precipitins) or microbiological evidence of Aspergillus infection (growth of Aspergillus in respiratory secretions or serum galactomannan index >0.5 or BALF galactomannan index >1) and,
  • exclusion of other pulmonary disorders with similar presentation.

Exclusion Criteria:

  • failure to provide informed consent
  • patients on immunosuppressive drugs, intake of prednisolone (or equivalent) >10 mg for at least 3 weeks or a diagnosis of human immunodeficiency virus syndrome
  • intake antifungal azoles for >3 weeks in the preceding six months
  • subjects with active pulmonary infection due to mycobacterium tuberculosis or mycobacteria other than tuberculosis (MOTT)
  • subjects with others forms of pulmonary aspergillosis (allergic bronchopulmonary aspergillosis, chronic necrotizing aspergillosis and angio-invasive aspergillosis)
  • pregnancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03920527
Other Study ID Numbers  ICMJE NK/4947/Res/986
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Inderpaul singh, Postgraduate Institute of Medical Education and Research
Study Sponsor  ICMJE Postgraduate Institute of Medical Education and Research
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Postgraduate Institute of Medical Education and Research
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP