Six Months Versus 12 Months of Oral Itraconazole Therapy for Management of Treatment naïve Subjects With CPA
Primary Purpose
Chronic Pulmonary Aspergillosis
Status
Completed
Phase
Phase 3
Locations
India
Study Type
Interventional
Intervention
Itraconazole 400 mg
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Pulmonary Aspergillosis focused on measuring CPA, Aspergillosis, CCPA, CFPA
Eligibility 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
Sites / Locations
- Inderpaul Singh
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Six months
12 months
Arm Description
Six months of itraconazole
12-months of itraconazole
Outcomes
Primary Outcome Measures
Relapse rate
number of relapses at 2 year after randomization
Secondary Outcome Measures
Response
Proportion of subjects with an overall favourable response at the end of oral itraconazole therapy
Adverse events
adverse events due to itraconazole
Full Information
NCT ID
NCT03920527
First Posted
April 9, 2019
Last Updated
October 11, 2021
Sponsor
Postgraduate Institute of Medical Education and Research
1. Study Identification
Unique Protocol Identification Number
NCT03920527
Brief Title
Six Months Versus 12 Months of Oral Itraconazole Therapy for Management of Treatment naïve Subjects With CPA
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
July 1, 2019 (Actual)
Primary Completion Date
July 1, 2021 (Actual)
Study Completion Date
August 15, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Postgraduate Institute of Medical Education and Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Pulmonary Aspergillosis
Keywords
CPA, Aspergillosis, CCPA, CFPA
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
164 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Six months
Arm Type
Active Comparator
Arm Description
Six months of itraconazole
Arm Title
12 months
Arm Type
Experimental
Arm Description
12-months of itraconazole
Intervention Type
Drug
Intervention Name(s)
Itraconazole 400 mg
Other Intervention Name(s)
sporanox
Intervention Description
Duration of itraconazole
Primary Outcome Measure Information:
Title
Relapse rate
Description
number of relapses at 2 year after randomization
Time Frame
2 year after randomization
Secondary Outcome Measure Information:
Title
Response
Description
Proportion of subjects with an overall favourable response at the end of oral itraconazole therapy
Time Frame
at 6 to 12 months
Title
Adverse events
Description
adverse events due to itraconazole
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Inderpaul Singh
City
Chandigarh
ZIP/Postal Code
160012
Country
India
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35429465
Citation
Sehgal IS, Dhooria S, Muthu V, Prasad KT, Aggarwal AN, Chakrabarti A, Choudhary H, Garg M, Agarwal R. Efficacy of 12-months oral itraconazole versus 6-months oral itraconazole to prevent relapses of chronic pulmonary aspergillosis: an open-label, randomised controlled trial in India. Lancet Infect Dis. 2022 Jul;22(7):1052-1061. doi: 10.1016/S1473-3099(22)00057-3. Epub 2022 Apr 13. Erratum In: Lancet Infect Dis. 2023 Feb;23(2):e47.
Results Reference
derived
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Six Months Versus 12 Months of Oral Itraconazole Therapy for Management of Treatment naïve Subjects With CPA
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