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terminated due to an inability to recruit study subjects
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| Name | Class |
|---|---|
| Eastern Virginia Medical School | OTHER |
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This study is designed as a masked, two center, randomized, placebo-controlled pilot study to evaluate the safety and efficacy of nasal and oral inhalation of 75 mg aztreonam in subjects with CF and lung infection due to PA. The study will involve two sites: Virginia Commonwealth University Medical Center (VCU) and Eastern Virginia Medical School (EVMS). Potential subjects will be identified in each site's CF clinic.
This study is designed to explore the efficacy and safety of nasal aztreonam administered using the Pari Sinus Nebulizer combined with oral Cayston aerosol therapy compared to placebo on clinical and laboratory endpoints such as risk of antibiotic-resistant Pseudomonas aeruginosa (PA), time to pulmonary infection exacerbation, nasal quality of life, pulmonary function, nasal and lower airway cultures, and properties of mucus.
P. aeruginosa (PA) is a primary cause of lung infections in persons with cystic fibrosis (CF) (1). Over the past decade, studies have shown that aerosolized antibiotics can reduce lower respiratory bacterial load, decrease exacerbations of pulmonary disease, and in many patients improve pulmonary function. Cayston (aztreonam) oral aerosol using the PARI Altera Nebulizer System was approved by the FDA in February 2010 for CF patients 7 years of age or older with PA (2). In 2011, 35.8% or patients in the National CF Patient Registry used Cayston for treatment (3). Bacterial cultures suggest that the upper airways and lower airways of CF patients are cross-infected by PA and that the paranasal sinuses can act as a bacterial reservoir (4). There is improved post-transplanation patient survival for recipients that undergo sinus surgery and daily nasal washes to reduce bacterial load (2).
Routine CF care does not generally include upper airway assessment. There are no published studies evaluating the effect of aerosol antibiotics to treat nasal and sinus infections in CF in combination with oral inhaled aerosol therapy to treat the lower airway disease. However Mainz and colleagues published a case report that suggested that sinonasal administration of tobramycin using the Pari Sinus nebulizer (Pari Corp, Starnberg, Germany) delayed PA lower respiratory infection in a 12 year-old with CF who had chronic mucopurulent rhinosinusitis (5) and studies in chronic obstructive pulmonary disease suggest that treating upper airways can also improve coexistent lower airway disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard Therapy | Active Comparator | Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Nasal Placebo-Normal Saline twice per day |
|
| Study Therapy | Experimental | Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Experimental- Nasal Aztreonam 75 mg twice per day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Aztreonam | Drug | Standard Therapy Comparator (Oral Cayston 75mg three times a day) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Protocol-defined Pulmonary Exacerbations Treated With IV Anti-pseudomonal Antibiotics on Day 140 | Protocol-Defined Pulmonary Exacerbation includes events that are characterized by change or worsening pulmonary symptoms (increased cough, increased sputum production and chest congestion, decreased appetite and exercise tolerance), loss of weight, and lung function decline that prompt initation of antibiotic therapy. Protocol-defined exacerbations in subjects that warrant treatment with IV antibiotics will be determined from the medical record during the course of this study. | 140 days |
| Measure | Description | Time Frame |
|---|---|---|
| Time to First Protocol-defined Pulmonary Exacerbation Treated With IV Anti-pseudomonal Antibiotics | Protocol-Defined Pulmonary Exacerbation includes events that are characterized by change or worsening pulmonary symptoms (increased cough, increased sputum production and chest congestion, decreased appetite and exercise tolerance), loss of weight, and lung function decline that prompt initation of antibiotic therapy. Protocol-defined exacerbations in subjects that warrant treatment with IV antibiotics will be determined from the medical record during the course of this study. The time of beginning the study to first protocol-defined pulmonary exacerbation will also be determined from the medical record during the course of this study. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bruce K Rubin, MD | Virginia Commonwealth University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Richmond at VCU | Richmond | Virginia | 23298 | United States |
Individual participant data will be deidentified and will not be availalble.
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard Therapy | Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Nasal Placebo-Normal Saline twice per day Oral Aztreonam: Standard Therapy Comparator (Oral Cayston 75mg three times a day) Nasal Placebo: Placebo (nasal saline twice per day) |
| FG001 | Study Therapy | Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Experimental- Nasal Aztreonam 75 mg twice per day Oral Aztreonam: Standard Therapy Comparator (Oral Cayston 75mg three times a day) Nasal Aztreonam: Study Therapy (nasal Aztreonam 75mg twice per day) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Because of the low number of enrollees with only 1 in the treatment group, results are not reported to protect the confidentiality of the participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Standard Therapy | Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Nasal Placebo-Normal Saline twice per day Oral Aztreonam: Standard Therapy Comparator (Oral Cayston 75mg three times a day) Nasal Placebo: Placebo (nasal saline twice per day) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Protocol-defined Pulmonary Exacerbations Treated With IV Anti-pseudomonal Antibiotics on Day 140 | Protocol-Defined Pulmonary Exacerbation includes events that are characterized by change or worsening pulmonary symptoms (increased cough, increased sputum production and chest congestion, decreased appetite and exercise tolerance), loss of weight, and lung function decline that prompt initation of antibiotic therapy. Protocol-defined exacerbations in subjects that warrant treatment with IV antibiotics will be determined from the medical record during the course of this study. | Because of the low number of enrollees with only 1 in the treatment group, results are not reported to protect the confidentiality of the participants | Posted | 140 days |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard Therapy | Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Nasal Placebo-Normal Saline twice per day Oral Aztreonam: Standard Therapy Comparator (Oral Cayston 75mg three times a day) Nasal Placebo: Placebo (nasal saline twice per day) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bruce K. Rubin MEngr, MD, MBA, FRCPC | Virginia Commonwealth University | 804 828 9604 | bruce.rubin@vcuhealth.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 3, 2017 | Dec 11, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D001398 | Aztreonam |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D008997 | Monobactams |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 |
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| Nasal Aztreonam | Drug | Study Therapy (nasal Aztreonam 75mg twice per day) |
|
|
| Nasal Placebo | Drug | Placebo (nasal saline twice per day) |
|
|
| Up to 6 months |
| Change in Sinus and Nasal QoL Questionnaire (SNOT-20) on Day 140 and Day 168 | The Sino-Nasal Outcome Test 20 (SNOT-20) is a validated health-related QOL questionnarie designed to determine the impact of sinonasal dysfunction. Patients will assess nasal symptoms, emotion, and activity on a scale of worsening symptoms scored 1 through 7 to provide a quantifiable score capable of disease severity. It has been shown as a responsive measure of health-related quality of life and suitable for use in outcomes studies and routine clinical care. Survey responses from Day 140 and Day 168 will be compared to the SNOT20 survey responses from previous visits (V1, V2, and V4) | Day 140 and Day 168 |
| Change in Cystic Fibrosis QoL Score (CFQ-R) on Day 140 | The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Visits 1, 6, and 7. The endpoint was change in CFQR on day 140 compared to V1 and V5. | Day 140 |
| Change in Pulmonary Function (FVC and FEV1 Percent Predicted) on Day 140 | Routine spirometry will be performed according to American Thoracic Society (ATS) guidelines. A minimum of three maneuvers will be performed. The largest FVC and FEV1 will be reported after examining data from all acceptable curves even if they did not originate from the same maneuver. Data will be expressed both in absolute values and as percent (%) predicted based upon NHANES predicted values. | Day 140 |
| Change in Paired Sputum Cultures and Nasal Swabs for Bacteria and Antibiotic Resistance | Expectorated sputum and nasal swabs will be cultured at each visit using standardized procedures to identify CF pathogens as well as susceptibility to a standard panel of antibiotics. | 1 year |
| Change in Acoustic Rhinometry for Nasal Obstruction (Volume) (Will be Measured at VCU Site ). | Acoustic rhinometry is used to measure cross-sectional volume of the nasal cavity allowing the calculation of nasal volume. Reflected sound waves are painlessly introduced through nasal adaptors into the nasal passages allowing the production of area-distance graphs. | 1 year |
| Number of Safety and Adverse Events Including Nasal Stuffiness, Epistaxis, and Headache. | The frequency, severity and duration of all nasal and pulmonary adverse events, regardless of cause, will be recorded in REDCap as an electronic case report form. Serious adverse events will be captured in OnCore. The frequency and severity of adverse events will be calculated for each patient, with each patient counted once using the most severe grade experienced. The duration of adverse events will be calculated by the number of days each event persisted. Tables will be generated for all adverse events including serious adverse events and withdraws from the study. | 1 year |
| Number of Protocol-defined Pulmonary Exacerbations Treated With Oral Anti-pseudomonal Antibiotics | Protocol-Defined Pulmonary Exacerbation includes events that are characterized by change or worsening pulmonary symptoms (increased cough, increased sputum production and chest congestion, decreased appetite and exercise tolerance), loss of weight, and lung function decline that prompt initation of antibiotic therapy. Protocol-defined exacerbations in subjects that warrant treatment with oral antibiotics will be determined from the medical record during the course of this study. | 1 year |
| BG001 |
| Study Therapy |
Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Experimental- Nasal Aztreonam 75 mg twice per day Oral Aztreonam: Standard Therapy Comparator (Oral Cayston 75mg three times a day) Nasal Aztreonam: Study Therapy (nasal Aztreonam 75mg twice per day) |
| BG002 | Total | Total of all reporting groups |
| Sex: Female, Male |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. |
| Region of Enrollment | participants |
|
| OG001 | Study Therapy | Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Experimental- Nasal Aztreonam 75 mg twice per day Oral Aztreonam: Standard Therapy Comparator (Oral Cayston 75mg three times a day) Nasal Aztreonam: Study Therapy (nasal Aztreonam 75mg twice per day) |
|
| Secondary | Time to First Protocol-defined Pulmonary Exacerbation Treated With IV Anti-pseudomonal Antibiotics | Protocol-Defined Pulmonary Exacerbation includes events that are characterized by change or worsening pulmonary symptoms (increased cough, increased sputum production and chest congestion, decreased appetite and exercise tolerance), loss of weight, and lung function decline that prompt initation of antibiotic therapy. Protocol-defined exacerbations in subjects that warrant treatment with IV antibiotics will be determined from the medical record during the course of this study. The time of beginning the study to first protocol-defined pulmonary exacerbation will also be determined from the medical record during the course of this study. | Because of the low number of enrollees with only 1 in the treatment group, results are not reported to protect the confidentiality of the participants | Posted | Up to 6 months |
|
|
| Secondary | Change in Sinus and Nasal QoL Questionnaire (SNOT-20) on Day 140 and Day 168 | The Sino-Nasal Outcome Test 20 (SNOT-20) is a validated health-related QOL questionnarie designed to determine the impact of sinonasal dysfunction. Patients will assess nasal symptoms, emotion, and activity on a scale of worsening symptoms scored 1 through 7 to provide a quantifiable score capable of disease severity. It has been shown as a responsive measure of health-related quality of life and suitable for use in outcomes studies and routine clinical care. Survey responses from Day 140 and Day 168 will be compared to the SNOT20 survey responses from previous visits (V1, V2, and V4) | Because of the low number of enrollees with only 1 in the treatment group, results are not reported to protect the confidentiality of the participants | Posted | Day 140 and Day 168 |
|
|
| Secondary | Change in Cystic Fibrosis QoL Score (CFQ-R) on Day 140 | The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Visits 1, 6, and 7. The endpoint was change in CFQR on day 140 compared to V1 and V5. | Because of the low number of enrollees with only 1 in the treatment group, results are not reported to protect the confidentiality of the participants | Posted | Day 140 |
|
|
| Secondary | Change in Pulmonary Function (FVC and FEV1 Percent Predicted) on Day 140 | Routine spirometry will be performed according to American Thoracic Society (ATS) guidelines. A minimum of three maneuvers will be performed. The largest FVC and FEV1 will be reported after examining data from all acceptable curves even if they did not originate from the same maneuver. Data will be expressed both in absolute values and as percent (%) predicted based upon NHANES predicted values. | Because of the low number of enrollees with only 1 in the treatment group, results are not reported to protect the confidentiality of the participants | Posted | Day 140 |
|
|
| Secondary | Change in Paired Sputum Cultures and Nasal Swabs for Bacteria and Antibiotic Resistance | Expectorated sputum and nasal swabs will be cultured at each visit using standardized procedures to identify CF pathogens as well as susceptibility to a standard panel of antibiotics. | Because of the low number of enrollees with only 1 in the treatment group, results are not reported to protect the confidentiality of the participants | Posted | 1 year |
|
|
| Secondary | Change in Acoustic Rhinometry for Nasal Obstruction (Volume) (Will be Measured at VCU Site ). | Acoustic rhinometry is used to measure cross-sectional volume of the nasal cavity allowing the calculation of nasal volume. Reflected sound waves are painlessly introduced through nasal adaptors into the nasal passages allowing the production of area-distance graphs. | Because of the low number of enrollees with only 1 in the treatment group, results are not reported to protect the confidentiality of the participants | Posted | 1 year |
|
|
| Secondary | Number of Safety and Adverse Events Including Nasal Stuffiness, Epistaxis, and Headache. | The frequency, severity and duration of all nasal and pulmonary adverse events, regardless of cause, will be recorded in REDCap as an electronic case report form. Serious adverse events will be captured in OnCore. The frequency and severity of adverse events will be calculated for each patient, with each patient counted once using the most severe grade experienced. The duration of adverse events will be calculated by the number of days each event persisted. Tables will be generated for all adverse events including serious adverse events and withdraws from the study. | Because of the low number of enrollees with only 1 in the treatment group, results are not reported to protect the confidentiality of the participants | Posted | 1 year |
|
|
| Secondary | Number of Protocol-defined Pulmonary Exacerbations Treated With Oral Anti-pseudomonal Antibiotics | Protocol-Defined Pulmonary Exacerbation includes events that are characterized by change or worsening pulmonary symptoms (increased cough, increased sputum production and chest congestion, decreased appetite and exercise tolerance), loss of weight, and lung function decline that prompt initation of antibiotic therapy. Protocol-defined exacerbations in subjects that warrant treatment with oral antibiotics will be determined from the medical record during the course of this study. | Because of the low number of enrollees with only 1 in the treatment group, results are not reported to protect the confidentiality of the participants | Posted | 1 year |
|
|
| 0 |
| 2 |
| 0 |
| 2 |
| 0 |
| 2 |
| EG001 | Study Therapy | Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Experimental- Nasal Aztreonam 75 mg twice per day Oral Aztreonam: Standard Therapy Comparator (Oral Cayston 75mg three times a day) Nasal Aztreonam: Study Therapy (nasal Aztreonam 75mg twice per day) | 0 | 1 | 0 | 1 | 0 | 1 |
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| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| Organic Chemicals |
| D013457 | Sulfur Compounds |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |