AspergillomaPhase 2/3NCT03799809
Efficacy of Intrabronchial Voriconazole Instillation for Inoperable Pulmonary Aspergilloma
A Phase 2/3 study testing Intrabronchial Voriconazole instillation in people with Aspergilloma, run by All India Institute of Medical Sciences at 1 site in India.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aspergilloma
- What is being tested?
- Intrabronchial Voriconazole instillation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteIndia
- Study dates
- 1 Dec 2016to 30 Jan 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with mild to moderate hemoptysis AND inoperable aspergilloma/ those unwilling for surgery.
- Who have no contra-indication of flexible fibre-optic bronchoscopy
- Age > 18 yrs AND
- Given the written informed consent to participate in the study.
Who cannot join
- Patient who are not fit for FOB (e.g. hemodynamic instability)
- Patient who have life threatening hemoptysis requiring immediate bronchial artery embolization
- Patients who have underwent BAE in last 3 months
- Pregnant woman
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
All India Institute of Medical Sciences
New Delhi, National Capital Territory of Delhi, 110029
Sachin D, MD, 8129840208, sachinmedico@gmail.com
About this study
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.
Read more
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.
Read the detailed description
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:
- To compare the percentage of patients who have complete cessation of hemoptysis after 3 months.
- To compare the percentage of patients having recurrence of hemoptysis during 3 months follow up.
- To compare the severity of hemoptysis during recurrence in both groups.
- To compare the change in size of aspergilloma after 3 - 6 months following last intrabronchial voriconazole instillation.
- To compare the percentage of patients who need BAE during anytime till 3 - 6months.
- 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.
- Conditions
- Aspergilloma
- Being tested
- Intrabronchial Voriconazole instillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrabronchial Voriconazole instillationDrug
Efficacy of intrabronchial voriconazole instillation for inoperable pulmonary aspergilloma
| Study group | Role | What they receive |
|---|---|---|
| Voriconazole | Active comparator | Will receive 400 mg of Intrabronchial Voriconazole every week for 4 weeks along with standard medical therapy. Receives: Drug: Intrabronchial Voriconazole instillation |
| Control | No intervention | Will receive standard medical therapy alone (hemostatics, anti-tussive and others as deemed appropriate by treating physician) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 pulmonary aspergilloma at 3 months.
Percentage of patients achieving reduction in hemoptysis in intrabronchial voriconazole with standard medical therapy group vs standard medical therapy alone for inoperable pulmonary aspergilloma at 3 months.
Measured: 3 months follow up
Secondary outcomes (6)
To compare the percentage of patients who have complete cessation of hemoptysis after 3 months.
percentage of patients who have complete cessation of hemoptysis after 3 months.
Measured: 3 months follow up
To compare the percentage of patients having recurrence of hemoptysis during 3 months follow up.
percentage of patients having recurrence of hemoptysis during 3 months follow up.
Measured: 3 months follow up
To compare the severity of hemoptysis during recurrence in both groups.
severity of hemoptysis during recurrence in both groups shall be compared with visual analogue scale.
Measured: 3 months follow up
To compare the change in size of aspergilloma after 3 months following last intrabronchial voriconazole instillation.
change in size of aspergilloma after 3 months following last intrabronchial voriconazole instillation.
Measured: 3 months follow up
To compare the percentage of patients who need BAE during anytime till 3 months.
percentage of patients who need BAE during anytime till 3 months.
Measured: 3 months follow up
To compare the percentage of patients with symptomatic improvement in Dyspnea On Exertion, Cough and hemoptysis.
percentage of patients with symptomatic improvement in Dyspnea On Exertion, Cough and hemoptysis.
Measured: 3 months follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2019
- Study start1 Dec 2016
- Primary completion30 Dec 2018 (estimated)
- Study completion30 Jan 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AspergillomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, DR SACHIN D, All India Institute of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03799809
- Sponsor's protocol ID
- AIIMS SACHIN
- Status last verified
- Jan 2019
- First submitted
- 20 Oct 2018
- Last updated
- 10 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Intrabronchial Voriconazole Instillation for Inoperable Pulmonary Aspergilloma- a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03799809
- Acronym / sponsor ID
- AIIMS SACHIN
- Conditions
- Aspergilloma
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- All India Institute of Medical SciencesUniversity, hospital or other
- Study start
- 1 Dec 2016 (actual)
- Primary completion
- 30 Dec 2018 (estimated)
- Study completion
- 30 Jan 2019 (estimated)
- First posted
- 10 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- To compare the percentage of patients who have complete cessation of hemoptysis after 3 months.
- To compare the percentage of patients having recurrence of hemoptysis during 3 months follow up.
- To compare the severity of hemoptysis during recurrence in both groups.
- To compare the change in size of aspergilloma after 3 - 6 months following last intrabronchial voriconazole instillation.
- To compare the percentage of patients who need BAE during anytime till 3 - 6months.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Voriconazole | Active comparator | Drug: Intrabronchial Voriconazole instillationWill receive 400 mg of Intrabronchial Voriconazole every week for 4 weeks along with standard medical therapy. |
| Control | No intervention | –Will receive standard medical therapy alone (hemostatics, anti-tussive and others as deemed appropriate by treating physician) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with mild to moderate hemoptysis AND inoperable aspergilloma/ those unwilling for surgery.
- Who have no contra-indication of flexible fibre-optic bronchoscopy
- Age > 18 yrs AND
- Given the written informed consent to participate in the study.
Key exclusion criteria (4 listed)
- Patient who are not fit for FOB (e.g. hemodynamic instability)
- Patient who have life threatening hemoptysis requiring immediate bronchial artery embolization
- Patients who have underwent BAE in last 3 months
- Pregnant woman
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intrabronchial Voriconazole instillationEfficacy of intrabronchial voriconazole instillation for inoperable pulmonary aspergilloma | Drug | Voriconazole |
Primary outcome
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 pulmonary aspergilloma at 3 months.
Time frame: 3 months follow up
Percentage of patients achieving reduction in hemoptysis in intrabronchial voriconazole with standard medical therapy group vs standard medical therapy alone for inoperable pulmonary aspergilloma at 3 months.
6 secondary outcomes
To compare the percentage of patients who have complete cessation of hemoptysis after 3 months.
Time frame: 3 months follow up
To compare the percentage of patients having recurrence of hemoptysis during 3 months follow up.
Time frame: 3 months follow up
To compare the severity of hemoptysis during recurrence in both groups.
Time frame: 3 months follow up
To compare the change in size of aspergilloma after 3 months following last intrabronchial voriconazole instillation.
Time frame: 3 months follow up
To compare the percentage of patients who need BAE during anytime till 3 months.
Time frame: 3 months follow up
To compare the percentage of patients with symptomatic improvement in Dyspnea On Exertion, Cough and hemoptysis.
Time frame: 3 months follow up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- Individual participant dataSharing planned: No
Related trials for Aspergilloma
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A Trial to Compare Nebulized Amphotericin B and Nebulized Normal Saline as Maintenance in Patients With Chronic Pulmonary Aspergillosis
Chronic Pulmonary Aspergillosis, CPA
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Intrabronchial Voriconazole instillation in people with Aspergilloma, run by All India Institute of Medical Sciences at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact SACHIN D, MD (8129840208, sachinmedico@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 pulmonary aspergilloma at 3 months. (time frame: 3 months follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2019.