Voriconazole Versus Oral Steroids in Allergic Bronchopulmonary Aspergillosis

A Randomized Controlled Trial of Voriconazole in Allergic Bronchopulmonary Aspergillosis

This is a research project to evaluate the efficacy and safety of two different treatment protocols in Allergic bronchopulmonary Aspergillosis.

Study Overview

• Status: Completed
• Conditions: Allergic Bronchopulmonary Aspergillosis
• Intervention / Treatment: Drug: Prednisolone; Drug: Voriconazole

Detailed Description

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused by a complex hypersensitivity response to antigens released by the fungus Aspergillus fumigatus. The management of ABPA includes two important aspects - institution of immunosuppressive therapy in the form of glucocorticoids to control the immunologic activity, and close monitoring for detection of relapses. Another possible target is to use antifungal agents to attenuate the fungal burden secondary to the fungal colonization in the airways. Oral corticosteroids are currently the treatment of choice for ABPA associated with bronchial asthma.They not only suppress the immune hyperfunction but are also anti-inflammatory. However, there is no data to guide the dose and duration of glucocorticoids and different regimens of glucocorticoids have been used in literature.Itraconazole, an oral triazole with relatively low toxicity, is active against Aspergillus spp. in vitro and in vivo. The activity of itraconazole against Aspergillus spp. is more than that of ketoconazole. The administration of itraconazole can eliminate Aspergillus in the airways and can theoretically reduce the allergic responses in ABPA. The new triazoles, such as voriconazole, have recently been found effective in the treatment of fungal infections. The investigators hypothesize that voriconazole might also be useful in the treatment of ABPA. The aim of this prospective randomized controlled trial (RCT) is to evaluate the efficacy and safety of voriconazole therapy in patients with ABPA.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• India
  • Chandigarh, India, 160012
    • Postgraduate Institute of Medical Education and Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Presence of all the following three criteria:

• Immediate cutaneous hyperreactivity on aspergillus skin test
• Elevated total IgE levels > 1000 IU/mL
• A fumigatus specific IgE levels > 0.35 kUA/L

And, two of the following criteria:

• Presence of serum precipitating antibodies against A fumigatus
• Fixed or transient radiographic pulmonary opacities
• Total eosinophil count > 1000/µL
• Central bronchiectasis on HRCT

Exclusion Criteria:

• Failure to give informed consent
• Intake of glucocorticoids for more than three weeks in the preceding six months
• Enrollment in another trial of ABPA
• Any exposure to azoles in the last six months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Steroid group	Drug: Prednisolone; 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 by 5 mg every 4 weeks and discontinue. Patients will also receive inhaled formoterol/fluticasone (6/125 mcg) 1 puff BD and as needed as per the SMART approach for control of asthma
EXPERIMENTAL: Voriconazole group	Drug: Voriconazole; Voriconazole 200 mg BD for 4 months. Patients will also receive inhaled formoterol/fluticasone (6/125 mcg) 1 puff BD and as needed as per the SMART approach for control of asthma; Other Names: Voritek 200 mg twice daily for four months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rates in the two groups	IgE levels decline by >=25 percent and there is clinical improvement with partial/total clearance of chest radiographic lesions [if pulmonary opacities have been previously present] after six and three months of treatment	Six weeks and three months
Relapse rates in the two groups	No ABPA exacerbations over the next 3 months after stopping therapy	12, 18, 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	Adverse events in the two groups	4 months

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Collaborators: Cipla Ltd.

Publications and helpful links

General Publications

• Agarwal R, Dhooria S, Sehgal IS, Aggarwal AN, Garg M, Saikia B, Chakrabarti A. A randomised trial of voriconazole and prednisolone monotherapy in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Eur Respir J. 2018 Sep 18;52(3):1801159. doi: 10.1183/13993003.01159-2018. Print 2018 Sep. No abstract available.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): April 1, 2016
• Study Completion (ACTUAL): April 1, 2016

Study Registration Dates

• First Submitted: June 12, 2012
• First Submitted That Met QC Criteria: June 15, 2012
• First Posted (ESTIMATE): June 18, 2012

Study Record Updates

• Last Update Posted (ACTUAL): December 12, 2017
• Last Update Submitted That Met QC Criteria: December 11, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bacterial Infections and Mycoses; Respiratory Hypersensitivity; Hypersensitivity; Mycoses; Lung Diseases, Fungal; Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Prednisolone; Voriconazole
• Other Study ID Numbers: ABPA/003