Trial record 5 of 6 for:    Open Studies | "Aspergillosis, Allergic Bronchopulmonary"

Monotherapy of Itraconazole Versus Prednisolone in Allergic Bronchopulmonary Aspergillosis (MIPA)

This study is currently recruiting participants.
Verified November 2012 by Postgraduate Institute of Medical Education and Research
Sponsor:
Information provided by (Responsible Party):
Ritesh Agarwal, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier:
NCT01321827
First received: March 23, 2011
Last updated: November 29, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to evaluate the efficacy and safety of itraconazole monotherapy in patients with ABPA.


Condition Intervention Phase
Allergic Bronchopulmonary Aspergillosis
Drug: Glucocorticoids
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Postgraduate Institute of Medical Education and Research:

Primary Outcome Measures:
  • Remission rates in the two groups at six weeks and three months [ Time Frame: 6 weeks, 3 months ] [ Designated as safety issue: No ]
    Remission - if the IgE levels decline by >=25% and there is clinical improvement with partial/total clearance of chest radiographic lesions after three months of glucocorticoids (if previously present pulmonary opacities)

  • Percentage decline in IgE levels at six weeks and three months [ Time Frame: 6 weeks, 3 months ] [ Designated as safety issue: No ]
    IgE levels will be noted at baseline six weeks and three months after glucocorticoid therapy and percentage decline will be calculated as: (baseline IgE levels minus IgE levels after six weeks of treatment) divided by baseline IgE levels

  • Complete remission rates in the two groups [ Time Frame: 3 months, 6 months ] [ Designated as safety issue: No ]
    No ABPA exacerbations over the next 3 months after stopping therapy


Secondary Outcome Measures:
  • Relapse rates in the two groups at six and 12 months after completion of treatment [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
    Relapse - doubling of the baseline IgE levels irrespective of the patient's symptoms or appearance of radiologic infiltrates

  • Treatment related adverse effects in the two groups [ Time Frame: Every 6 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: January 2011
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Itraconazole group
Itraconazole 200 mg BD for 4 months along with inhaled formoterol/fluticasone (6/125 mcg) 2 puffs twice daily by MDI and as needed as per the SMART approach
Drug: Glucocorticoids
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 2 weeks and discontinue. Patients will also receive inhaled formoterol/fluticasone (6/125 mcg) as needed as per the SMART approach for control of asthma
Other Name: Prednisolone

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 clinical entity was first described by Hinson et al in 1952, and the clinical and immunologic significance of Aspergillus fumigatus in the sputum were reported by Pepys and coworkers in 1959. The prevalence of ABPA in bronchial asthma is fairly high and a recent meta-analysis suggested the prevalence of ABPA in asthma clinics to be as high as 13 percent. Diagnostic criteria for ABPA have been laid and generally include the following eight major criteria: (a) history of asthma; (b) transient or fixed pulmonary infiltrates; (c) immediate cutaneous hyperreactivity to A fumigatus antigen; (d) absolute eosinophil count > 1000/µL; (e) serum precipitins against A fumigatus; (f) total IgE levels > 1000 IU/mL; (g) central bronchiectasis on high-resolution computed tomography (HRCT); and, (h) raised A fumigatus specific IgE or IgG levels. However, none of these are specific for ABPA,and there is still no consensus on the number of criteria needed for diagnosis, and patients in different stages of ABPA may not fulfill all these criteria. Also, there is no established definition for remission of ABPA. The most widely followed criteria are clinical and radiological improvement with at least 35 percent decline in total serum IgE levels. However, in a recent study the investigators demonstrated that a 35% decline in serum IgE levels at six weeks is not seen in all patients with ABPA, and the decline is slower in patients with baseline IgE levels < 2500 IU/mL. Moreover, the quantum decline in serum IgE levels did not predict clinical outcome. The disorder is highly prevalent in India. The investigators have previously reported our experience with screening stable outpatients with bronchial asthma and acute severe asthma for ABPA. The investigators have also recently reported the prognostic factors associated with clinical outcomes in patients with ABPA.

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 aim of this prospective randomized controlled trial (RCT) is to evaluate the efficacy and safety of itraconazole monotherapy in patients with ABPA.

  Eligibility

Ages Eligible for Study:   12 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Patients will be included in the study if they meet the criteria for ABPA defined by

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 kU/L

Two of the following criteria:

  • presence of serum precipitating antibodies against A fumigatus
  • fixed or transient radiographic pulmonary opacities
  • absolute eosinophil count > 1000/µL
  • central bronchiectasis on HRCT.

Exclusion Criteria:

  • if they have taken glucocorticoids for more than three weeks in the preceding six months
  • failure to give informed consent
  • enrollment in another trial of ABPA
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01321827

Contacts
Contact: Ritesh Agarwal, MD, DM +911722756825 riteshpgi@gmail.com

Locations
India
Postgraduate Institute of Medical Education and Research Recruiting
Chandigarh, UT, India, 160012
Contact: Ritesh Agarwal, MD, DM    +911722756825    riteshpgi@gmail.com   
Principal Investigator: Ritesh Agarwal, MD, DM         
Sub-Investigator: Ashutosh N Aggarwal, MD, DM         
Sub-Investigator: Dheeraj Gupta, MD, DM         
Sub-Investigator: Mandeep Garg, MD         
Sub-Investigator: Biman Saikia, MD         
Sub-Investigator: Arunaloke Chakrabarti, MD         
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Investigators
Principal Investigator: Ritesh Agarwal, MD, DM PGIMER, Chandigarh
  More Information

No publications provided

Responsible Party: Ritesh Agarwal, Associate Professor, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT01321827     History of Changes
Other Study ID Numbers: IGCST, MS/1398/Res/1838
Study First Received: March 23, 2011
Last Updated: November 29, 2012
Health Authority: India: Dept of Pulmonary Medicine

Keywords provided by Postgraduate Institute of Medical Education and Research:
ABPA

Additional relevant MeSH terms:
Aspergillosis, Allergic Bronchopulmonary
Aspergillosis
Pulmonary Aspergillosis
Mycoses
Lung Diseases, Fungal
Lung Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Respiratory Tract Infections
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Glucocorticoids
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Methylprednisolone acetate
Prednisolone acetate
Itraconazole
Hydroxyitraconazole
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 17, 2014