Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04227483 |
| Other study ID # |
RA/2020/001 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
January 15, 2020 |
| Est. completion date |
December 2024 |
Study information
| Verified date |
November 2023 |
| Source |
Postgraduate Institute of Medical Education and Research |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Oral glucocorticoids are currently the treatment of choice for allergic bronchopulmonary
aspergillosis (ABPA). They not only suppress the immune hyperfunction but are also
anti-inflammatory. Unfortunately, numerous toxicities and adverse effects have been
attributed to glucocorticoids related to both the average dose and cumulative duration of
use.
Deflazacort is a oxazoline steroid with demonstrated anti-inflammatory and immunosuppressant
effects. The novel structural characteristic of deflazacort is associated with substantial
lack of sodium-retaining activity, lower interference with carbohydrate metabolism and
calcium metabolism in comparison with older glucocorticoids such as prednisolone. The
investigators hypothesize that the occurrence of side-effects, primarily weight gain will be
lower with deflazacort. In this study, the investigators will compare the safety and efficacy
of deflazacort in the treatment of acute-stage ABPA complicating asthma.
Description:
Depending on the host immunity and the organism virulence, the respiratory diseases caused by
Aspergillus are classified as saprophytic (aspergilloma), allergic (allergic aspergillus
sinusitis and allergic bronchopulmonary aspergillosis) and invasive (acute invasive pulmonary
aspergillosis, subacute invasive pulmonary aspergillosis and chronic pulmonary
aspergillosis). Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused
by a complex hypersensitivity response to the antigens released by the fungus Aspergillus
fumigatus. The disorder clinically manifests as chronic asthma, recurrent pulmonary
infiltrates, and bronchiectasis. The clinical entity was first described by Hinson et al in
1952,4 and the clinical and immunologic significance of Aspergillus fumigatus in the sputum
were reported by Pepys and coworkers in 1959.5 The condition has immunologic features of
immediate hypersensitivity (type I), antigen-antibody complexes (type III), and
eosinophil-rich inflammatory cell responses (type IVb), based on the revised Gell and Coombs
classification of immunologic hypersensitivity. Occasionally, patients can develop a syndrome
similar to ABPA but is caused by fungi other than A.fumigatus and is termed as allergic
bronchopulmonary mycosis. The condition remains underdiagnosed in many countries with reports
of mean diagnostic latency of ten years between the occurrence of symptoms and the
diagnosis.9 In the past two decades, there has been an increase in the number of cases of
ABPA due to the heightened physician awareness and the widespread availability of serologic
assays.
The diagnostic criteria for ABPA have been recently revised and includes the following: (a)
history of asthma; (b) pulmonary opacities consistent with ABPA; (c) raised A. fumigatus
specific IgE >0.35 kUA/L; (d) peripheral blood eosinophil count >500 cells/µL; (e) raised A.
fumigatus specific IgG levels >27 mgA/L; (f) total IgE levels >1000 IU/mL. 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. The global burden of ABPA has been
estimated to be about 5 million cases. The disorder is highly prevalent in India, and there
are an estimated 1.4 million cases in India alone.
Oral glucocorticoids are currently the treatment of choice for ABPA. They not only suppress
the immune hyperfunction but are also anti-inflammatory. Different regimens of
glucocorticoids have been used in literature. In a recent study, it was found that lower
doses of glucocorticoids are as effective as higher doses in the therapy of acute-stage ABPA.
Unfortunately, numerous toxicities and adverse effects have been attributed to
glucocorticoids related to both the average dose and cumulative duration of use. The serious
toxicities include hyperglycemia, increased loss of bone mineral density, reports of
avascular necrosis, myopathy, excess cardiovascular events or heart disease, increased blood
pressure, serious cutaneous side effects, upper gastrointestinal ulcers or bleeding,
pancreatitis, increased risk of infection, psychosis, or mood disturbances. In one study, the
average daily dose of glucocorticoid was the strongest predictor of a serious side-effect
potentially attributable to glucocorticoid (prednisone) therapy (odds ratio of 4.5 and 32.3
for 5-10 mg and 10-15 mg prednisone, respectively). In another study, the risk of adverse
events with low-dose glucocorticoids (prednisone 5-10 mg/day) was small. However, even with
low-dose steroid there is an increase in body weight including the appearance of cushingoid
facies.
Deflazacort is a heterocyclic glucocorticoid prodrug belonging to the class of oxazoline
steroids, with demonstrated anti-inflammatory and immunosuppressant effects. The novel
structural characteristic of deflazacort is associated with substantial lack of
sodium-retaining activity, lower interference with carbohydrate metabolism and calcium
metabolism (with lower propensity for bone loss) in comparison with older glucocorticoids
such as prednisolone. The investigators hypothesize that the occurrence of side-effects,
primarily weight gain will be lower with deflazacort.
In this study, the investigators will compare the safety and efficacy of deflazacort in the
treatment of acute-stage ABPA complicating asthma.
