search
Back to results

Oral Itraconazole Versus Combination of Systemic Glucorticoids and Oral Itraconazole in CPA-ABPA Overlap Syndrome (GLITZ)

Primary Purpose

Chronic Pulmonary Aspergillosis, Allergic Bronchopulmonary Aspergillosis

Status
Recruiting
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Prednisone tablet and Itraconazole
Oral itraconazole
Sponsored by
Postgraduate Institute of Medical Education and Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Pulmonary Aspergillosis

Eligibility Criteria

15 Years - 90 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects fulfil criteria for ABPA and CPA as below.

The criteria for CPA would include the presence of all the following: (i) one or more clinical symptoms (persistent cough, recurrent hemoptysis, weight loss, malaise, fever and dyspnea) for ≥3 months; (ii) slowly progressive or persistent 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; (iii) immunological (A.fumigatus-specific IgG >27 mgA/L or positive Aspergillus precipitins) or microbiological evidence of Aspergillus infection (growth of Aspergillus in respiratory secretions) and, (iv) exclusion of other pulmonary disorders with similar presentation.

The diagnosis of ABPA will be made based on the presence of all the following: (a) A.fumigatus specific IgE >0.35 kUA/L; (b) total IgE ≥500 IU/mL; (c) eosinophil count ≥500 cells/µL); (d) A.fumigatus IgG>27 mgA/L.

Exclusion Criteria:

(i) failure to provide informed consent; (ii) patients on immunosuppressive drugs, intake of prednisolone (or equivalent) >10 mg for at least 3 weeks or a diagnosis of human immunodeficiency virus syndrome; (iii) intake of antifungal triazoles for >3 weeks in the preceding three months; (iv) subjects with active pulmonary infection due to mycobacterium tuberculosis or mycobacteria other than tuberculosis (MOTT); (v) subjects with others forms of pulmonary aspergillosis (subacute and acute invasive aspergillosis); and, (vi) pregnancy.

Sites / Locations

  • Chest clinic, PGIMER
  • Chest clinicRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Steroid itraconazole

Itraconazole

Arm Description

Combination of oral glucocorticoid (prednisolone 0.5 mg/Kg body weight tapered over 4 months) and itraconazole for 12 months

Oral itraconazole for 12 months

Outcomes

Primary Outcome Measures

Favourable response at six months after the randomization
Proportion of subjects with an overall favourable response at six months after the randomization. The overall response will be categorized as favourable: improved or stable clinical response with radiologically improved or stable disease

Secondary Outcome Measures

Overall favourable response at 12 months after randomization
Proportion of subjects with an overall favourable response at 12 months after the randomization. The overall response will be categorized as favourable: improved or stable clinical response with radiologically improved or stable disease
frequency of relapses at 18-months after randomization
Relapse: will be defined as persistent worsening of symptoms (for 14 days or more) as measured by VAS and radiological worsening. The subjects will be investigated for other causes of worsening such as bacterial infection or reinfection/reactivation of tuberculosis before labelling the worsening due to relapse of CPA. A relapse will be defined as an event that occurs 3 months after stopping treatment
adverse events in either arm
Adverse events due to systemic glucocorticoids and oral itraconazole will be assessed at 2 weeks after treatment initiation and then at 3 months interval till treatment completion
Serum total IgE response to treatment
proportion of subjects with 25% reduction in serum IgE at 6 weeks after treatment initiation
Serum total IgE during relapse
Proportion of subjects with 50% increase in serum IgE during relapse

Full Information

First Posted
June 21, 2022
Last Updated
March 21, 2023
Sponsor
Postgraduate Institute of Medical Education and Research
search

1. Study Identification

Unique Protocol Identification Number
NCT05444946
Brief Title
Oral Itraconazole Versus Combination of Systemic Glucorticoids and Oral Itraconazole in CPA-ABPA Overlap Syndrome
Acronym
GLITZ
Official Title
A Randomized Controlled Trial to Compare Oral Itraconazole Versus Combination of Systemic Glucorticoids and Oral Itraconazole in Chronic Pulmonary and Allergic Bronchopulmonary Aspergillosis Overlap Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

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
While ABPA and CPA represent two distinct manifestations of Aspergillus-related lung disease, there is an overlap of investigations that are currently used for the diagnosis of these entities. In a previous study, the authors have demonstrated that 22% of subjects with CPA fulfilled the obligatory criteria for ABPA. While the preferable therapy in patients with ABPA is systemic glucocorticoids, the primary therapy in CPA is oral triazoles. However, a different management protocol in the "overlap group" with low doses of glucocorticoids and triazoles, needs to be systematically explored. In this study the investigators intend to compare the clinical outcomes in subjects with ABPA-CPA overlap treated either with oral azoles or a combination of systemic glucocorticoids and oral azoles.
Detailed Description
Aspergillus causes a variety of pulmonary disorders depending on the host immunity. In immunocompetent hosts, it can cause allergic diseases, the prototype being allergic bronchopulmonary aspergillosis (ABPA). In immunosuppressed host, it causes life-threatening invasive disease. Chronic pulmonary aspergillosis (CPA) represents chronic Aspergillus infection of the pulmonary parenchyma in subjects with normal or slightly suppressed immunity, and generally an underlying structural lung disease (previously treated pulmonary tuberculosis, chronic obstructive pulmonary disease, sarcoidosis, diffuse parenchymal lung disease and others). The diagnosis of CPA is based on the presence of clinical symptoms (low-grade fever, weight loss, malaise, chronic cough, recurrent hemoptysis and others), radiological features (combination of one or more cavities and presence of fungal ball or fibrosis, pericavitary infiltrates, consolidation, nodules and pleural thickening) and the demonstration of either direct (growth of Aspergillus on sputum or bronchoalveolar lavage fluid [BALF] culture) or indirect (elevated serum or BALF galactomannan index or A.fumigatus-specific IgG or precipitin in serum) evidence of Aspergillus infection. Primarily seen in patients with asthma and cystic fibrosis, the diagnosis of ABPA is currently made on the combination of clinical (low grade fever, hemoptysis and others), radiological (bronchiectasis, mucus impaction, centrilobular nodules and others) and immunological (A.fumigatus-specific IgE and IgG, total IgE, and elevated eosinophils) findings. While ABPA and CPA represent two distinct manifestations of Aspergillus-related lung disease, there is an overlap of investigations that are currently used for the diagnosis of these entities. For example, A.fumigatus-specific IgG and Aspergillus precipitins are used both in diagnosing ABPA and CPA.(10) The culture of respiratory tract secretions can demonstrate the growth of Aspergillus in both these disorders. Also, ABPA is a predisposing condition for developing CPA and it is likely that both ABPA and CPA may coexist. In a previous study, the authors have demonstrated that 22% of subjects with CPA fulfilled the obligatory criteria for ABPA. While CPA is primarily due to dysfunction of Th-1 immunity, ABPA represents an inflammatory response due to Th-2 hyper response. Thus, it is possible that subjects with ABPA-CPA overlap could have components of both heightened inflammatory response and local immune dysfunction thereby perpetuating structural lung damage. While the preferable therapy in patients with ABPA is systemic glucocorticoids, the primary therapy in CPA is oral triazoles. However, a different management protocol in the "overlap group" with low doses of glucocorticoids and triazoles, needs to be systematically explored. In this study the investigators intend to compare the clinical outcomes in subjects with ABPA-CPA overlap treated either with oral azoles or a combination of systemic glucocorticoids and oral azoles.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Pulmonary Aspergillosis, Allergic Bronchopulmonary Aspergillosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Subjects with CPA-ABPA overlap will be randomized to receive either a combination of systemic steroids and oral itraconazole or oral itraconazole alone
Masking
None (Open Label)
Allocation
Randomized
Enrollment
104 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Steroid itraconazole
Arm Type
Experimental
Arm Description
Combination of oral glucocorticoid (prednisolone 0.5 mg/Kg body weight tapered over 4 months) and itraconazole for 12 months
Arm Title
Itraconazole
Arm Type
Active Comparator
Arm Description
Oral itraconazole for 12 months
Intervention Type
Drug
Intervention Name(s)
Prednisone tablet and Itraconazole
Other Intervention Name(s)
sporanox
Intervention Description
Oral prednisolone 0.5 mg/Kg body weight tapered over 4 months and oral itraconazole (400 mg/day). The dose of itraconazole will be adjusted according to therapeutic drug monitoring to achieve a serum trough level of 0.5 microgram/mL. traconazole will be given for 12 months
Intervention Type
Drug
Intervention Name(s)
Oral itraconazole
Other Intervention Name(s)
sporanox
Intervention Description
Oral itraconazole (400 mg/day). The dose of itraconazole will be adjusted according to therapeutic drug monitoring to achieve a serum trough level of 0.5 microgram/mL. Itraconazole will be given for 12 months
Primary Outcome Measure Information:
Title
Favourable response at six months after the randomization
Description
Proportion of subjects with an overall favourable response at six months after the randomization. The overall response will be categorized as favourable: improved or stable clinical response with radiologically improved or stable disease
Time Frame
6 months after randomization
Secondary Outcome Measure Information:
Title
Overall favourable response at 12 months after randomization
Description
Proportion of subjects with an overall favourable response at 12 months after the randomization. The overall response will be categorized as favourable: improved or stable clinical response with radiologically improved or stable disease
Time Frame
12 months after randomization
Title
frequency of relapses at 18-months after randomization
Description
Relapse: will be defined as persistent worsening of symptoms (for 14 days or more) as measured by VAS and radiological worsening. The subjects will be investigated for other causes of worsening such as bacterial infection or reinfection/reactivation of tuberculosis before labelling the worsening due to relapse of CPA. A relapse will be defined as an event that occurs 3 months after stopping treatment
Time Frame
18 months after randomization
Title
adverse events in either arm
Description
Adverse events due to systemic glucocorticoids and oral itraconazole will be assessed at 2 weeks after treatment initiation and then at 3 months interval till treatment completion
Time Frame
12 months after randomization
Title
Serum total IgE response to treatment
Description
proportion of subjects with 25% reduction in serum IgE at 6 weeks after treatment initiation
Time Frame
6 weeks after treatment initiation
Title
Serum total IgE during relapse
Description
Proportion of subjects with 50% increase in serum IgE during relapse
Time Frame
18 months after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects fulfil criteria for ABPA and CPA as below. The criteria for CPA would include the presence of all the following: (i) one or more clinical symptoms (persistent cough, recurrent hemoptysis, weight loss, malaise, fever and dyspnea) for ≥3 months; (ii) slowly progressive or persistent 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; (iii) immunological (A.fumigatus-specific IgG >27 mgA/L or positive Aspergillus precipitins) or microbiological evidence of Aspergillus infection (growth of Aspergillus in respiratory secretions) and, (iv) exclusion of other pulmonary disorders with similar presentation. The diagnosis of ABPA will be made based on the presence of all the following: (a) A.fumigatus specific IgE >0.35 kUA/L; (b) total IgE ≥500 IU/mL; (c) eosinophil count ≥500 cells/µL); (d) A.fumigatus IgG>27 mgA/L. Exclusion Criteria: (i) failure to provide informed consent; (ii) patients on immunosuppressive drugs, intake of prednisolone (or equivalent) >10 mg for at least 3 weeks or a diagnosis of human immunodeficiency virus syndrome; (iii) intake of antifungal triazoles for >3 weeks in the preceding three months; (iv) subjects with active pulmonary infection due to mycobacterium tuberculosis or mycobacteria other than tuberculosis (MOTT); (v) subjects with others forms of pulmonary aspergillosis (subacute and acute invasive aspergillosis); and, (vi) pregnancy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Inderpaul S Sehgal, MD, DM
Phone
91-172275
Ext
6823
Email
inderpgi@outlook.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ritesh Agarwal, MD,DM
Phone
91-172275
Ext
6825
Email
agarwal.ritesh@outlook.in
Facility Information:
Facility Name
Chest clinic, PGIMER
City
Chandigarh
ZIP/Postal Code
160012
Country
India
Individual Site Status
Active, not recruiting
Facility Name
Chest clinic
City
Chandigarh
ZIP/Postal Code
160012
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Inderpaul S Sehgal, MD,DM
Phone
+91-172275
Ext
6823
Email
inderpgi@outlook.com

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
IPD will be shared on email to the corresponding author

Learn more about this trial

Oral Itraconazole Versus Combination of Systemic Glucorticoids and Oral Itraconazole in CPA-ABPA Overlap Syndrome

We'll reach out to this number within 24 hrs