A Randomized Trial of Prednisolone, Itraconazole, or Their Combination in Allergic Bronchopulmonary Aspergillosis

NCT06174922 | Recruiting Phase 3 DMC

• 1 other identifier: Int/IEC/2023/SPL-1026A
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that a combination of prednisolone and itraconazole would significantly reduce the exacerbation rate at one-year of patients with acute allergic bronchopulmonary aspergillosis (ABPA) compared to itraconazole or prednisolone monotherapy. In this study, 300 subjects aged ≥18 years with acute ABPA will be randomized to treatment with either prednisolone, itraconazole, or prednisolone plus itraconazole, all for four months each. After collecting baseline demographic, immunologic, and imaging data, the investigators will follow the patients every 2 months for the first two visits and then every four months for three visits. The primary outcome will be the proportion of subjects experiencing exacerbation (asthma or ABPA) 12 months after treatment completion.

Conditions

Allergic Bronchopulmonary Aspergillosis

Outcome Measures

Primary Outcomes (1)

• Asthma or ABPA exacerbations

  Proportion of subjects experiencing exacerbation (asthma or ABPA) 12 months after treatment completion

  12 months after treatment completion

Secondary Outcomes (8)

• Composite response

  8 weeks

• IgE decline

  8 weeks

• Time to first ABPA exacerbation

  12 months after treatment completion

• Time to first asthma exacerbation

  12 months after treatment completion

• Weight gain

  Two months

Study Arms (3)

Prednisolone

ACTIVE COMPARATOR

Oral prednisolone 0.5 mg/kg/day for 4 weeks; 0.25 mg/kg/day for 4 weeks; 0.125 mg/kg/day for 4 weeks. Then taper 5 mg every 4 weeks and discontinue by 4 months. After breakfast, oral prednisolone will be administered as a morning dose (8-10 am).

Drug: Prednisolone

Itraconazole

ACTIVE COMPARATOR

Oral SUBA-itraconazole 65 mg 2 capsules BD for 4 months. Oral itraconazole will be given twice daily (9 am and 9 pm) spaced one hour with meals. We will perform therapeutic drug monitoring for itraconazole at two weeks and two months. We will increase the itraconazole dose to a maximum of 390 mg/day (six 65 mg capsules) in those with trough itraconazole levels \<0.5 µg/mL.

Drug: Itraconazole

Prednisolone plus itraconazole

EXPERIMENTAL

Oral prednisolone 0.5 mg/kg/day for 4 weeks; 0.25 mg/kg/day for 4 weeks; 0.125 mg/kg/day for 4 weeks. Then taper 5 mg every 4 weeks and discontinue by 4 months. After breakfast, oral prednisolone will be administered as a morning dose (8-10 am); and, Oral SUBA-itraconazole 65 mg 2 capsules BD for 4 months. Oral itraconazole will be given twice daily (9 am and 9 pm) spaced one hour with meals. We will perform therapeutic drug monitoring for itraconazole at two weeks and two months. We will increase the itraconazole dose to a maximum of 390 mg/day (six 65 mg capsules) in those with trough itraconazole levels \<0.5 µg/mL.

Drug: Prednisolone; Drug: Itraconazole

Interventions

Prednisolone DRUG

Prednisolone for 4 months

Prednisolone; Prednisolone plus itraconazole

Itraconazole DRUG

SUBA-itraconazole for 4 months

Itraconazole; Prednisolone plus itraconazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Consecutive subjects of acute stage allergic bronchopulmonary aspergillosis (ABPA) complicating asthma per the revised ISHAM-ABPA working group criteria
• newly diagnosed subjects with uncontrolled asthma or symptoms or radiology suggesting active lesions attributable to ABPA and meeting the diagnostic criteria of ABPA
• those previously meeting the diagnostic criteria for ABPA and presenting with sustained (≥2 weeks) clinical or radiological worsening; and increase in serum total IgE by ≥50% of the last recorded IgE value during clinical stability.

You may not qualify if:

• occurrence of ≥3 ABPA exacerbations in the last 18 months before enrollment
• contraindications to the use of either prednisolone or itraconazole
• subjects who have received oral prednisolone (or equivalent) ≥30 mg for ≥2 weeks or itraconazole (or voriconazole or posaconazole or isavuconazole) for more than 2 weeks, in the last 3 months
• chronic medical illnesses, including uncontrolled diabetes mellitus, chronic renal failure, chronic liver failure, chronic heart failure, and others
• patient on immunosuppressive drugs
• pregnancy
• enrollment in another trial of ABPA
• failure to provide informed consent
• asthma exacerbation: worsening respiratory symptoms for at least 24 hours without immunological or radiological deterioration of ABPA
• infective/bronchiectasis exacerbation: clinical deterioration for at least 24 hours with increase in cough; breathlessness; sputum volume or consistency; sputum purulence; fatigue, malaise, or fever; and hemoptysis without immunological or radiological deterioration of ABPA
• serologic ABPA

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

Chest Clinic, Dept. of Pulmonary Medicine

Chandigarh, Chandigarh, 160012, India

RECRUITING

MeSH Terms

Conditions

Aspergillosis, Allergic Bronchopulmonary

Interventions

Prednisolone; Itraconazole

Condition Hierarchy (Ancestors)

Pulmonary Aspergillosis; Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Lung Diseases, Fungal; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 24, 2023
• First Posted: December 18, 2023
• Study Start: December 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 28, 2025

Record last verified: 2025-02

Locations

IN (1)