A Trial to Compare Nebulized Amphotericin B and Nebulized Normal Saline as Maintenance in Patients With Chronic Pulmonary Aspergillosis

NCT06447402 | Recruiting Phase 3 DMC

• 1 other identifier: SPL-577
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 1

Brief Summary

The treatment of CPA is with oral itraconazole for 6-12 months. Oral itraconazole results in better clinical outcomes in CPA compared to supportive care. A recent study comparing 6 months with 12 months of oral itraconazole for longer duration treatment found longer duration reduced CPA relapse and improved clinical outcomes. However, longer duration of itraconazole could cause emergence of drug resistant Aspergillus fumigatus and therapy related adverse event. A recent study found nebulized amphotericin B non-inferior to oral itraconazole for treating CPA as primary therapy. However, the study was small and included patients with simple aspergilloma and used nebulized amphotericin B for 7 days.To be effective, an inhaled drug should be delivered in sufficient quantity to achieve therapeutic levels.The minimum inhibitory concentration of amphotericin B for A.fumigatus is 0.5 mg/L. In one study, nebulization of 30 mg of amphotericin B deoxycholate achieved a mean concentration of 0.68 mg/L in the bronchoalveolar lavage fluid. Notably, the serum levels of amphotericin B after nebulization are 20 times less than after systemic administration and is safer. Further, there is a dose-response relation with nebulized amphotericin B, the higher the dose used for nebulization, the higher are the levels achieved in the lung tissue. Nebulized amphotericin B has been used in lung transplant recipients to prevent invasive aspergillosis. Also, two recent studies have demonstrated that use of nebulized amphotericin B as maintenance therapy led to a reduction in ABPA relapse rates and prolonged time to exacerbation. We believe that inhaled amphotericin B as a maintenance therapy could reduce CPA relapse and prolong time to relapse. In this study, we plan to evaluate nebulized amphotericin B as a maintenance therapy in clinically stable CPA patients treated with 12 months of oral antifungal therapy

Conditions

Chronic Pulmonary Aspergillosis; CPA; Aspergilloma

Keywords

CCPA; CFPA; CPA; Post TB lung abnormality; PTLD

Outcome Measures

Primary Outcomes (1)

• Time to first exacerbation

  Time to exacerbation of CPA after stopping itraconazole

  12 months after randomization

Secondary Outcomes (2)

• frequency of relapses at 12-months after randomization

  12 months after randomization

• Treatment emergent adverse events

  12 months after randomization

Study Arms (2)

Saline arm

PLACEBO COMPARATOR

5 ml normal saline will be given as nebulization

Drug: Normal saline

NAB arm

EXPERIMENTAL

Amphotericin B dexoycholate will be nebulised twice daily

Drug: Amphotericin B deoxycholate

Interventions

Normal saline DRUG

5 mL of normal saline will be nebulised in the control arm

Saline arm

Amphotericin B deoxycholate DRUG

2 mL of the above reconstituted amphotericin B solution will be obtained in a sterile syringe and transferred into the drug chamber of a nebulizer. Three mL of distilled water will be added to 2 mL of the reconstituted amphotericin B (5 mL liquid in the chamber ensures complete and easy nebulization of all the contents)

NAB arm

Eligibility Criteria

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

You may qualify if:

• consecutive subjects with CPA who have received 12 months therapy with oral itraconazole

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (1)

Chest clinic

Chandigarh, 160012, India

RECRUITING

MeSH Terms

Interventions

Saline Solution; amphotericin B, deoxycholate drug combination

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Inderpaul S Sehgal, MD, DM

CONTACT

91-172-2756823; inderpgi@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessor will be blinded to patient allocation
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 7, 2024
• Study Start: June 3, 2024
• Primary Completion (Estimated): June 3, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: June 10, 2024

Record last verified: 2024-06

Locations

IN (1)