Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04824417 |
| Other study ID # |
PGI/IEC/2019/002366 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2021 |
| Est. completion date |
May 31, 2024 |
Study information
| Verified date |
June 2024 |
| Source |
Post Graduate Institute of Medical Education and Research, Chandigarh |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The current initial therapy for CPA is with six months of oral itraconazole. However, the
response with six months of therapy has a response rate of 65-70% and has a relapse rate
after stopping treatment of up to 50%. Voriconazole is a third-generation azole and a
theoretical advantage of lower MICs compared to itraconazole. Also, oral voriconazole has
good availability (95%) in fasting state. This is likely to improve the response rate and
reduce the chances of relapse of chronic pulmonary aspergillosis. There is no head to head
comparison of oral itraconazole with oral voriconazole. In this study we intent to compare
the clinical outcomes with six months of therapy with oral itraconazole versus oral
voriconazole for management of treatment naïve subjects with chronic pulmonary aspergillosis
Description:
Aspergillus is a saprophytic fungus which is present normally in our surroundings and causes
a large number of pulmonary diseases spreading through inhalational route. The spectrum of
disease caused by aspergillus spp. is wide with the manifestations of the disease being
governed primarily by the status of the underlying host immunity, which then determines the
nature of the host-aspergillus interaction. Patients with an intact immunity have a more
stable and indolent form of disease like aspergilloma whereas with a worsening immune status,
the risk of invasive disease increases. Chronic pulmonary aspergillosis (CPA) and allergic
bronchopulmonary aspergillosis (ABPA) are two of the commonest pulmonary manifestations seen
in non-immunocompromised patients whereas invasive pulmonary aspergillosis being more common
in the immunocompromised patients.(1-3) Estimates suggest that CPA affects around 3 million
people across the globe, which may still be an under estimated number as the disease co
exists with other pulmonary co-morbidities which make accurate diagnosis a pitfall. In India
the annual incidence of CPA was estimated in 2011 and varied between 27,000-0.17 million
cases, with different estimates. Based on the mortality rate for CPA which was estimated to
be 15% annually, the 5-year prevalence of CPA was placed at 290,147 cases with 5-year
prevalence rate being 24 per 100,000 in the same year.(4, 5) The disease confers significant
morbidity and mortality, making it a significant burden for the society as well as the
healthcare. Apart from the respiratory symptoms, CPA causes significant constitutional
symptoms as well which adds to the misery of the patient. The diagnosis of CPA is based on
presence of chronic symptoms, consistent radiology and demonstration of Aspergillus by direct
(culture) or indirect (serological) methods.(1-3) Even though CPA is more of a disease
spectrum but overall it is characterized by slowly progressive lung cavitation which may or
may not show presence of mycetoma /fungal ball in patients with pre-existing structural lung
diseases, even though other patterns have also been identified.
The treatment options majorly consist of medical management with at least 6-month long
treatment with antifungal drugs - most significantly the azole groups. Itraconazole is the
preferred azole for the treatment of CPA.(6-8) However the response with itraconazole is seen
in around 60-75% of the subjects.(9) Moreover, about 30%-50% of the subjects have disease
relapse that requires prolonged therapy. The lower response could be because of variable
pharmacokinetics and drug absorption of oral itraconazole. Also, itraconazole has many drug
interactions. Voriconazole is a third-generation azole and is currently the therapy of choice
for invasive aspergillosis due to its lower minimal inhibitory concentration (MIC) values
compared to itraconazole. In addition, the pharmacokinetics of voriconazole are not variable
and oral form has a good bioavailability (up to 95%). In a previous study, the use of
voriconazole resulted in radiological control in 97% of the subjects and a significant
improvement in patients' symptoms but global success at six-months was only seen in 32%
subjects.(10) However, despite being multicenter the study only included 48 subjects.
Moreover, there was no control group and the authors did not use therapeutic dose monitoring.
In addition, the study also included subjects with subacute invasive aspergillosis (SAIA).
Thus, there is lack of information regarding the role of voriconazole in subjects with CPA.
We hypothesize that the use of voriconazole will be associated with better treatment outcomes
compared with oral itraconazole in treatment naïve subjects with CPA. In this randomized
controlled trial, we compare the clinical outcomes of six months therapy with oral
itraconazole with oral voriconazole in treatment naïve subjects with chronic pulmonary
aspergillosis.
REFERENCES
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Diagnosis and management of Aspergillus diseases: executive summary of the 2017
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publication of the European Society of Clinical Microbiology and Infectious Diseases.
2018.
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Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by
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9. Agarwal R, Vishwanath G, Aggarwal AN, Garg M, Gupta D, Chakrabarti A. Itraconazole in
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review of literature. Mycoses. 2013;56(5):559-70.
10. Cadranel J, Philippe B, Hennequin C, Bergeron A, Bergot E, Bourdin A, et al.
Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial.
European journal of clinical microbiology & infectious diseases : official publication
of the European Society of Clinical Microbiology. 2012;31(11):3231-9.
