Ignite Creation Date:
2024-06-16 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06447402
Status:
RECRUITING
Last Update Posted:
2024-06-10
First Post:
2024-06-03
Brief Title:
A Trial to Compare Nebulized Amphotericin B and Nebulized Normal Saline as Maintenance in Patients With Chronic Pulmonary Aspergillosis
Sponsor:
Post Graduate Institute of Medical Education and Research Chandigarh
Organization:
Post Graduate Institute of Medical Education and Research Chandigarh
Study Overview
Official Title:
A Randomized Controlled Trial to Compare Nebulized Amphotericin B and Nebulized Normal Saline as Maintenance in Increasing Time to Relapse in Patients With Chronic Pulmonary Aspergillosis Treated With 12 Months of Oral Itraconazole
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NAB-CPA
Brief Summary:
The treatment of CPA is with oral itraconazole for 6-12 months Oral itraconazole results in better clinical outcomes in CPA compared to supportive care A recent study comparing 6 months with 12 months of oral itraconazole for longer duration treatment found longer duration reduced CPA relapse and improved clinical outcomes However longer duration of itraconazole could cause emergence of drug resistant Aspergillus fumigatus and therapy related adverse event A recent study found nebulized amphotericin B non-inferior to oral itraconazole for treating CPA as primary therapy However the study was small and included patients with simple aspergilloma and used nebulized amphotericin B for 7 daysTo be effective an inhaled drug should be delivered in sufficient quantity to achieve therapeutic levelsThe minimum inhibitory concentration of amphotericin B for Afumigatus is 05 mgL In one study nebulization of 30 mg of amphotericin B deoxycholate achieved a mean concentration of 068 mgL in the bronchoalveolar lavage fluid Notably the serum levels of amphotericin B after nebulization are 20 times less than after systemic administration and is safer Further there is a dose-response relation with nebulized amphotericin B the higher the dose used for nebulization the higher are the levels achieved in the lung tissue Nebulized amphotericin B has been used in lung transplant recipients to prevent invasive aspergillosis Also two recent studies have demonstrated that use of nebulized amphotericin B as maintenance therapy led to a reduction in ABPA relapse rates and prolonged time to exacerbation We believe that inhaled amphotericin B as a maintenance therapy could reduce CPA relapse and prolong time to relapse In this study we plan to evaluate nebulized amphotericin B as a maintenance therapy in clinically stable CPA patients treated with 12 months of oral antifungal therapy
Detailed Description:
Aspergillus is a ubiquitous fungus that causes a spectrum of human lung diseases depending on the host immunity and the immune response In those with overt immunodeficiency Aspergillus spp causes invasive pulmonary aspergillosis In immunocompetent individuals with structurally damaged lungs Aspergillus spp causes chronic pulmonary aspergillosis On the other hand allergic bronchopulmonary aspergillosis ABPA complicated the disease course of asthmatics and cystic fibrosis due to a hyperimmune response mounted by the host against the fungi colonizing the airways
Chronic pulmonary aspergillosis CPA has significant global burden yet under-reported aspergillus related chronic lung disease CPA is a chronic progressive lung disease that has a five-year mortality of over 50 CPA has a significant global burden with more than a million individuals are affected with CPA globally In India alone more than 100000 individuals are affected with CPA annually CPA occurs primarily in patients with pre-existing structural lung disease including post-pulmonary tuberculosis lung disease PTBLD chronic obstructive pulmonary disease COPD and others In our experience PTBLD is the most common risk factor for CPA3-5 While the treatment of pulmonary TB is highly effective almost 25-30 of the cases are left with sequelae of the disease including cavities parenchymal fibrosis and others Patients with sequelae are not only at higher risk of recurrence of TB but are also prone to colonization with Aspergillus fumigatus It has been estimated that CPA develops in approximately 20-25 of treated pulmonary tuberculosis with residual cavity Unfortunately the recognition of CPA is poor amongst physicians and even pulmonary physicians Patients with recurrent cough hemoptysis fever or weight loss and a negative sputum examination for AFB or Xpert MTBRif are labelled as smear negative pulmonary tuberculosis In fact almost 50 of the patients with CPA are misdiagnosed as pulmonary TB and receive empiric anti-TB therapy because of the similarities in presentation of the two disorders Untreated CPA is fatal with a five-year mortality of 30-80This has clinical implications as these patients with CPA would benefit from antifungal agents While the actual burden of CPA among treated TB patients is not known a mathematical model estimated that approximately 014 million cases are affected annually Further it was shown that if the mortality of CPA is estimated as 15 annually the 5-year burden of CPA is about 290147 cases with a 5-year prevalence rate of 24 per 100000
The diagnosis of CPA is based on the constellation of clinical symptoms low-grade fever weight loss anorexia malaise cough with expectoration recurrent hemoptysis fatigue chest pain and dyspnea for at least three months persistent or progressive radiological features one or more cavities with or without fungal ball fibrosis pericavitary infiltrates consolidation nodules and pleural thickening and the presence of either direct positive sputum or bronchoalveolar lavage fluid BALF culture or indirect elevated serum or BALF galactomannan index or Aspergillus fumigatus-specific precipitins or IgG antibodies in serum evidence of Aspergillus infection Of the available diagnostic modalities serology is the most reliable component of the CPA diagnostic pathway Currently the estimation of Afumigatus-specific IgG by enzyme immunoassay Phadia Immulite and others is considered the most sensitive test in the diagnosis of CPA In a recent study using a cut-off of 27 mgAL the sensitivity of Afumigatus-specific IgG in the diagnosis of CPA was about 913The prevalence of CPA in India in subjects not known Our group has estimated the burden of CPA following pulmonary TB using a mathematical modelling
The treatment of CPA is with oral itraconazole for 6-12 months Oral itraconazole results in better clinical outcomes in CPA compared to supportive care A recent study comparing 6 months with 12 months of oral itraconazole for longer duration treatment found longer duration reduced CPA relapse and improved clinical outcomes However longer duration of itraconazole could cause emergence of drug resistant Aspergillus fumigatus and therapy related adverse event A recent study found nebulized amphotericin B non-inferior to oral itraconazole for treating CPA as primary therapy However the study was small and included patients with simple aspergilloma and used nebulized amphotericin B for 7 daysTo be effective an inhaled drug should be delivered in sufficient quantity to achieve therapeutic levels The minimum inhibitory concentration of amphotericin B for Afumigatus is 05 mgL In one study nebulization of 30 mg of amphotericin B deoxycholate achieved a mean concentration of 068 mgL in the bronchoalveolar lavage fluid Notably the serum levels of amphotericin B after nebulization are 20 times less than after systemic administration and is safer Further there is a dose-response relation with nebulized amphotericin B the higher the dose used for nebulization the higher are the levels achieved in the lung tissue Nebulized amphotericin B has been used in lung transplant recipients to prevent invasive aspergillosis Also two recent studies have demonstrated that use of nebulized amphotericin B as maintenance therapy led to a reduction in ABPA relapse rates and prolonged time to exacerbation We believe that inhaled amphotericin B as a maintenance therapy could reduce CPA relapse and prolong time to relapse In this study we plan to evaluate nebulized amphotericin B as a maintenance therapy in clinically stable CPA patients treated with 12 months of oral antifungal therapy
AIMS To compare the clinical outcomes of nebulized amphotericin B deoxycholate versus nebulized normal saline as maintenance therapy in CPA subjects treated with 12 months of antifungal therapy
Chronic pulmonary aspergillosis CPA has significant global burden yet under-reported aspergillus related chronic lung disease CPA is a chronic progressive lung disease that has a five-year mortality of over 50 CPA has a significant global burden with more than a million individuals are affected with CPA globally In India alone more than 100000 individuals are affected with CPA annually CPA occurs primarily in patients with pre-existing structural lung disease including post-pulmonary tuberculosis lung disease PTBLD chronic obstructive pulmonary disease COPD and others In our experience PTBLD is the most common risk factor for CPA3-5 While the treatment of pulmonary TB is highly effective almost 25-30 of the cases are left with sequelae of the disease including cavities parenchymal fibrosis and others Patients with sequelae are not only at higher risk of recurrence of TB but are also prone to colonization with Aspergillus fumigatus It has been estimated that CPA develops in approximately 20-25 of treated pulmonary tuberculosis with residual cavity Unfortunately the recognition of CPA is poor amongst physicians and even pulmonary physicians Patients with recurrent cough hemoptysis fever or weight loss and a negative sputum examination for AFB or Xpert MTBRif are labelled as smear negative pulmonary tuberculosis In fact almost 50 of the patients with CPA are misdiagnosed as pulmonary TB and receive empiric anti-TB therapy because of the similarities in presentation of the two disorders Untreated CPA is fatal with a five-year mortality of 30-80This has clinical implications as these patients with CPA would benefit from antifungal agents While the actual burden of CPA among treated TB patients is not known a mathematical model estimated that approximately 014 million cases are affected annually Further it was shown that if the mortality of CPA is estimated as 15 annually the 5-year burden of CPA is about 290147 cases with a 5-year prevalence rate of 24 per 100000
The diagnosis of CPA is based on the constellation of clinical symptoms low-grade fever weight loss anorexia malaise cough with expectoration recurrent hemoptysis fatigue chest pain and dyspnea for at least three months persistent or progressive radiological features one or more cavities with or without fungal ball fibrosis pericavitary infiltrates consolidation nodules and pleural thickening and the presence of either direct positive sputum or bronchoalveolar lavage fluid BALF culture or indirect elevated serum or BALF galactomannan index or Aspergillus fumigatus-specific precipitins or IgG antibodies in serum evidence of Aspergillus infection Of the available diagnostic modalities serology is the most reliable component of the CPA diagnostic pathway Currently the estimation of Afumigatus-specific IgG by enzyme immunoassay Phadia Immulite and others is considered the most sensitive test in the diagnosis of CPA In a recent study using a cut-off of 27 mgAL the sensitivity of Afumigatus-specific IgG in the diagnosis of CPA was about 913The prevalence of CPA in India in subjects not known Our group has estimated the burden of CPA following pulmonary TB using a mathematical modelling
The treatment of CPA is with oral itraconazole for 6-12 months Oral itraconazole results in better clinical outcomes in CPA compared to supportive care A recent study comparing 6 months with 12 months of oral itraconazole for longer duration treatment found longer duration reduced CPA relapse and improved clinical outcomes However longer duration of itraconazole could cause emergence of drug resistant Aspergillus fumigatus and therapy related adverse event A recent study found nebulized amphotericin B non-inferior to oral itraconazole for treating CPA as primary therapy However the study was small and included patients with simple aspergilloma and used nebulized amphotericin B for 7 daysTo be effective an inhaled drug should be delivered in sufficient quantity to achieve therapeutic levels The minimum inhibitory concentration of amphotericin B for Afumigatus is 05 mgL In one study nebulization of 30 mg of amphotericin B deoxycholate achieved a mean concentration of 068 mgL in the bronchoalveolar lavage fluid Notably the serum levels of amphotericin B after nebulization are 20 times less than after systemic administration and is safer Further there is a dose-response relation with nebulized amphotericin B the higher the dose used for nebulization the higher are the levels achieved in the lung tissue Nebulized amphotericin B has been used in lung transplant recipients to prevent invasive aspergillosis Also two recent studies have demonstrated that use of nebulized amphotericin B as maintenance therapy led to a reduction in ABPA relapse rates and prolonged time to exacerbation We believe that inhaled amphotericin B as a maintenance therapy could reduce CPA relapse and prolong time to relapse In this study we plan to evaluate nebulized amphotericin B as a maintenance therapy in clinically stable CPA patients treated with 12 months of oral antifungal therapy
AIMS To compare the clinical outcomes of nebulized amphotericin B deoxycholate versus nebulized normal saline as maintenance therapy in CPA subjects treated with 12 months of antifungal therapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None