Interferon-gamma as Adjunctive Therapy in Chronic Pulmonary Aspergillosis: a Randomised Feasibility Study
Status:
Not yet recruiting
Trial end date:
2025-09-01
Target enrollment:
Participant gender:
Summary
This study explores the role of treatment with interferon-gamma to improve outcomes in
chronic pulmonary aspergillosis (CPA). CPA is a progressive infection caused by the fungus
Aspergillus affecting patients with chronic lung disease like Chronic Obstructive Lung
Disease (COPD) or previously treated tuberculosis (TB). It causes gradual destruction of lung
tissue by slowly enlarging cavities, frequent secondary infections and poor quality of life.
Because of its indolent nature and nonspecific x-ray findings, it often remains unrecognised
for years. Around 3600 people live with CPA in the United Kingdom. Mortality from CPA may be
up to 40% in five years.
Treatment for CPA relies on antifungals for prolonged periods, but only around 60% of
patients improve. It is often long-term or lifelong as the response is slow and some patients
experience relapses. In addition, only one class of oral antifungal drugs is licensed for
CPA, and they are associated with side effects and high cost. Better treatments are needed
for CPA. We do not know why many patients do not respond to treatment. Maybe CPA patients
have a weakened immune system and are more susceptible to Aspergillus. Our data suggest that
CPA patients produce lower amounts of ΙFNγ, a substance that facilitates the immune system's
response against Aspergillus. We have also shown that, when given to patients with CPA who
have failed to improve on antifungal treatment, interferon-gamma leads to improvement in
important patient-centred outcomes like flares of lung disease or hospital admissions.
Interferon-gamma is already in use in the National Health Service of the United Kingdom for
other indications. Therefore, its use in CPA should be explored. However, CPA is a rare
condition and the tolerability of interferon-gamma is not fully established in these
patients. To understand whether a large-scale study is feasible in CPA, we first need
preliminary data in smaller numbers of patients.
We propose a randomised trial of interferon-gamma in addition to antifungals in CPA. Patients
with CPA starting antifungal treatment will be eligible. Participants (25 per group) will be
randomly assigned to interferon-gamma for 12 weeks (in addition to antifungals) or
antifungals only. To test whether the treatment works, we will use measurements of the
cavities on chest CT scan and scores on a quality-of-life questionnaire. We will assess for
tolerability of treatment at intervals similar to clinical practice. Criteria for progression
to the large-scale study will be set based on the proportion of patients willing to
participate, and on the proportion who complete the treatment. Data collected on those
parameters will allow us to determine the number needed for a definite study.
If the large-scale study confirms our observations that interferon-gamma improves outcomes in
CPA, then treatment duration can be shortened and relapses avoided. In addition,
interferon-gamma can then be explored in other chronic lung disease.