Aztreonam Aerosol to Treat Cystic Fibrosis Nasal Disease

• ClinicalTrials.gov Identifier: NCT02730793
• Recruitment Status: Terminated
• First Posted: April 6, 2016
• Results First Posted: January 12, 2021
• Last Update Posted: January 28, 2021
• Sponsor: Virginia Commonwealth University
• Collaborator: Eastern Virginia Medical School
• Information provided by (Responsible Party): Virginia Commonwealth University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Cystic Fibrosis
• Interventions: Drug: Oral Aztreonam; Drug: Nasal Aztreonam; Drug: Nasal Placebo
• Enrollment: 5

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Standard Therapy	Study Therapy
Arm/Group Description	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)	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)
Period Title: Overall Study
Started	2	3
Completed	2	1
Not Completed	0	2
Reason Not Completed
Physician Decision	0	1
Withdrawal by Subject	0	1

Baseline Characteristics

Arm/Group Title		Standard Therapy	Study Therapy	Total
Arm/Group Description		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)	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)	Total of all reporting groups
Overall Number of Baseline Participants		0	0	0
Baseline Analysis Population Description		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
Age, Continuous	Number Analyzed	0 participants	0 participants	0 participants
Sex: Female, Male
	Number Analyzed	0 participants	0 participants	0 participants
	Female
	Male
Race and Ethnicity Not Collected [1]	Number Analyzed	0 participants	0 participants	0 participants
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment; Unit of measure: Participants
United States	Number Analyzed	0 participants	0 participants	0 participants

Outcome Measures

1. Primary Outcome

Title	Number of Protocol-defined Pulmonary Exacerbations Treated With IV Anti-pseudomonal Antibiotics on Day 140
Description	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.
Time Frame	140 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Standard Therapy	Study Therapy
Arm/Group Description:	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)	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)
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

2. Secondary Outcome

Title	Time to First Protocol-defined Pulmonary Exacerbation Treated With IV Anti-pseudomonal Antibiotics
Description	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.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Standard Therapy	Study Therapy
Arm/Group Description:	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)	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)
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

3. Secondary Outcome

Title	Change in Sinus and Nasal QoL Questionnaire (SNOT-20) on Day 140 and Day 168
Description	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)
Time Frame	Day 140 and Day 168

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Standard Therapy	Study Therapy
Arm/Group Description:	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)	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)
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

4. Secondary Outcome

Title	Change in Cystic Fibrosis QoL Score (CFQ-R) on Day 140
Description	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.
Time Frame	Day 140

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Standard Therapy	Study Therapy
Arm/Group Description:	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)	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)
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

5. Secondary Outcome

Title	Change in Pulmonary Function (FVC and FEV1 Percent Predicted) on Day 140
Description	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.
Time Frame	Day 140

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Standard Therapy	Study Therapy
Arm/Group Description:	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)	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)
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

6. Secondary Outcome

Title	Change in Paired Sputum Cultures and Nasal Swabs for Bacteria and Antibiotic Resistance
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Standard Therapy	Study Therapy
Arm/Group Description:	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)	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)
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

7. Secondary Outcome

Title	Change in Acoustic Rhinometry for Nasal Obstruction (Volume) (Will be Measured at VCU Site ).
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Standard Therapy	Study Therapy
Arm/Group Description:	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)	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)
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

8. Secondary Outcome

Title	Number of Safety and Adverse Events Including Nasal Stuffiness, Epistaxis, and Headache.
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Standard Therapy	Study Therapy
Arm/Group Description:	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)	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)
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

9. Secondary Outcome

Title	Number of Protocol-defined Pulmonary Exacerbations Treated With Oral Anti-pseudomonal Antibiotics
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Standard Therapy	Study Therapy
Arm/Group Description:	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)	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)
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Standard Therapy	Study Therapy
Arm/Group Description	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)	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)
All-Cause Mortality
	Standard Therapy	Study Therapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/2 (0.00%)	0/1 (0.00%)
Serious Adverse Events
	Standard Therapy	Study Therapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/2 (0.00%)	0/1 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Standard Therapy	Study Therapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/2 (0.00%)	0/1 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Bruce K. Rubin MEngr, MD, MBA, FRCPC
• Organization: Virginia Commonwealth University
• Phone: 804 828 9604
• EMail: bruce.rubin@vcuhealth.org

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT02730793
• Other Study ID Numbers: HM20005657
• First Submitted: November 3, 2015
• First Posted: April 6, 2016
• Results First Submitted: December 17, 2020
• Results First Posted: January 12, 2021
• Last Update Posted: January 28, 2021