Aspergilloma Clinical Trial
Official title:
Efficacy of Intrabronchial Voriconazole Instillation for Inoperable Pulmonary Aspergilloma- a Randomized Controlled Trial
Pulmonary aspergillomas are a common cause of recurrent hemoptysis which may be moderate to
severe in 2 to 50 % of cases and may be life threatening. Surgical resection, though
curative, may not be feasible in significant number of patients and also associated
significant post op complications. Bronchial artery embolisation (BAE) is effective for acute
control of hemoptysis, however recurrences may occur in upto a quarter of subjects over a 1
year period.
Aspergilloma is caused by a fungus hence systemic antifungals seem appropriate choice.
However the fungus only partially touch the walls of the cavities containing them and rarely
come into contact with the bloodstream. This is the major reason why the systemic
administration of antifungal agents is ineffective in eradicating the condition.
If surgical resection is not a treatment option to control recurrent hemoptysis, instillation
of antifungal agents in an aspergilloma cavity could be considered(QoE II).The instillation
of antifungal directly into the cavity (intra-cavitatory) containing aspergilloma brings the
drug in contact with the fungus. Thus may lead to antifungal action and shrinkage or complete
disappearance of aspergilloma. This can be achieved either by percutaneous route or
bronchoscopically. Percutaneous approaches have been investigated however they can sometimes
cause fungal spread in thoracic space resulting in fungal empyema which should be carefully
avoided. Endobronchial instillation of antifungals have been investigated and found to be
safe and effective in controlling hemoptysis, however published data comprise of case reports
or small case series.
Recently we have published our experience of intrabronchial voriconazole in aspergilloma
among 82 patients and found to be safe and effective in hemoptysis control, with transient
post procedure cough as an adverse effect with no major serious adverse events. Multiple
small studies and case reports have published the safety and efficacy of voriconazole.
However, a quality data in the form of randomized controlled trial (RCT) is not there.
Therefore, we planned this RCT to assess the efficacy of intrabronchial voriconazole in
inoperable aspergilloma.
Primary Objective : To compare the percentage of patients achieving reduction in hemoptysis
in intrabronchial voriconazole with standard medical therapy group vs standard medical
therapy alone for inoperable symptomatic pulmonary aspergilloma.
Secondary Objectives:
1. To compare the percentage of patients who have complete cessation of hemoptysis after 3
months.
2. To compare the percentage of patients having recurrence of hemoptysis during 3 months
follow up.
3. To compare the severity of hemoptysis during recurrence in both groups.
4. To compare the change in size of aspergilloma after 3 - 6 months following last
intrabronchial voriconazole instillation.
5. To compare the percentage of patients who need BAE during anytime till 3 - 6months.
6. To compare the percentage of patients with symptomatic improvement in Dyspnea On
Exertion, Cough and recurrent respiratory infections.
Number of Patients: 30 patients in each arm (Intrabronchial voriconazole with Standard
medical therapy vs Standard medical therapy alone)
Study Design : Prospective Randomized control study
Dosages of drug - 400 mg iv preparation of Voriconazole every week for 4 sessions
Duration of follow-up - 3-6 months
Brief Methodology: Patients with aspergilloma who presented with hemoptysis will be screened
for inclusion in the study. Diagnosis of aspergilloma will be based on characteristic
computed tomography (CT) features with microbiological or serological evidence of Aspergillus
(Aspergillus specific Ig G). The patients fulfilling the inclusion criteria will be taken
informed consent and randomized into one of the two arms of intervention.
Arm 1: Will receive 400 mg of Intrabronchial Voriconazole every week for 4 weeks along with
standard medical therapy.
Arm 2: Will receive standard medical therapy alone (hemostatics, anti-tussive and others as
deemed appropriate by treating physician)
All subjects in arm 1 will undergo fiberoptic bronchoscopy (FOB) following standard protocol
under local anesthesia with supplemental oxygen and continuous hemodynamic monitoring. After
identifying the segmental/sub-segmental bronchus of interest (as identified by CT) or cavity
(if visible) the study drug voriconazole, will be instilled. The bronchoscope will be kept
wedged for 60 seconds to prevent back leakage of the solution and then slowly withdrawn
without applying suction. The patient will be kept in right or left lateral position
(depending on the side of involvement) for the next 20 minutes. Following this patients will
be observed for 48 hours for cessation of hemoptysis before discharge. The procedure will be
done on day 1 of each week for 4 weeks in arm 1.
All patients will receive standard medical treatment for hemoptysis including appropriate
positioning, airway protection, blood product transfusions, antitussives, tranexamic acid,
and antimicrobial therapy as clinically indicated. BAE shall be offered to all patients if
indicated.
Mild hemoptysis shall be defined as < 50 ml in 24 hrs, moderate hemoptysis as 50-200 ml in 24
hrs and massive hemoptysis as 200-600 ml in 24 hrs or any amount causing hemodynamic
compromise/threatening ventilation.
Records will be reviewed regarding demographics, primary etiology leading to fibrocavitary
disease, duration and severity of hemoptysis/ other constitutional symptoms, extent of
disease (unilateral, bilateral, associated pleural or parenchymal changes), simple vs complex
aspergilloma. Size of index aspergilloma. The number of patients requiring emergency or
hospital admission due to recurrent hemoptysis, and subsequent treatment details will be
recorded.
All patients will be followed up for 3-6 months. During follow up patients will be assessed
for symptoms and severity, successful cessation of hemoptysis, requirement of BAE due to
persistent or increased hemoptysis, number of sessions required for symptomatic
improvement/cessation of hemoptysis, hemoptysis-free interval, recurrence of hemoptysis will
be noted. Pre and post procedure CT scans (low dose limited CT through aspergilloma) will be
compared by an independent radiologist blinded to the clinical outcome. Size of index
aspergilloma shall be determined by addition of maximum diameter of largest length and width
of the visible lesion. CTs shall be compared for documenting change in the size of index
aspergilloma and decrease/disappearance of the cavity. On the basis of these parameters,
aspergillomas will be described as no interval change, increased or decreased aspergilloma
size, or disappearance and emptying of the cavity.
Outcomes in the form of reduction/cessation of hemoptysis, decrease in size of aspergilloma,
overall symptomatic improvement and mortality shall be recorded.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT06447402 -
A Trial to Compare Nebulized Amphotericin B and Nebulized Normal Saline as Maintenance in Patients With Chronic Pulmonary Aspergillosis
|
Phase 3 |