Cystic FibrosisPhase 2NCT02730793
Aztreonam Aerosol to Treat Cystic Fibrosis Nasal Disease
A Phase 2 study testing Oral Aztreonam and Nasal Aztreonam in people with Cystic Fibrosis, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 7 to 100 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Oral Aztreonam and Nasal Aztreonam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to 19 Sep 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 7 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Males or females 7 years of age or older and able to perform pulmonary function testing
- Confirmed diagnosis of CF by the 1997 CF Consensus Conference criteria and followed by the VCU or EVMS CF clinic
- Presence of PA in 2 lower respiratory tract (sputum) cultures in the 24 months before screening
- Subjects and/or parent guardian must be able to give written informed consent prior to any study related procedure
- All sexually active female subjects who are of childbearing potential must agree to use an effective method of contraception (i.e.condoms or abstinence).
- All sexually active female subjects must have a negative pregnancy test at screening (V0).
- Clinically stable determined by the study physician with no significant new respiratory symptoms.
- Presence of PA in nasal culture (swab or secretion) or sinus culture obtained in the 12 months before screening or at screening visit
Who cannot join
- Use of oral, IV or inhaled antibiotics within 0 days before study other than low dose azithromycin
- Severe pulmonary disease with FEV1<30% predicted of baseline SpO2<0.90
- ENT surgery within 6 months of screening
- Allergy or documented adverse reaction to aztreonam
- Epistaxis or significant (>30mL) hemoptysis in the past 6 months
- Frequent (weekly or more frequently) or severe headaches
Show all 11Show fewer
- Subject is unlikely to comply with the procedures scheduled in the protocol
- Subject participates in another clinical trial within 30 days prior to study entry
- Subjects who have had a lung transplant will be excluded
- Prisoners will be excluded
- Non-English Speaking patients will be excluded
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Richmond at VCU
Richmond, Virginia, 23298
About this study
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.
Read the detailed description
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.
- 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.
- Conditions
- Cystic Fibrosis
- Being tested
- Oral Aztreonam, Nasal Aztreonam, Nasal Placebo
- Keywords
- Cystic Fibrosis, P. aeruginosa (PA)
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral AztreonamDrug
Also called Cayston, Azactam
Standard Therapy Comparator (Oral Cayston 75mg three times a day)
Nasal AztreonamDrug
Also called Cayston, Azactam
Study Therapy (nasal Aztreonam 75mg twice per day)
Nasal PlaceboDrug
Also called Saline
Placebo (nasal saline twice per day)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Oral Aztreonam; Drug: Nasal Placebo |
| 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 Receives: Drug: Oral Aztreonam; Drug: Nasal Aztreonam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 140 days
Secondary outcomes (8)
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.
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2016 (estimated)
- Study startJan 2017
- Primary completion19 Sep 2019
- Study completion19 Sep 2019
Why it stopped: terminated due to an inability to recruit study subjects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- Eastern Virginia Medical School
- Responsible party
- Sponsor
- Investigators
- Bruce K Rubin, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02730793
- Sponsor's protocol ID
- HM20005657
- Status last verified
- Jan 2021
- First submitted
- 3 Nov 2015
- Last updated
- 28 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will be deidentified and will not be availalble.
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aztreonam Aerosol to Treat Cystic Fibrosis Nasal Disease
- ClinicalTrials.gov ID
- NCT02730793
- Acronym / sponsor ID
- HM20005657
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, P. aeruginosa (PA)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: terminated due to an inability to recruit study subjects
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- Eastern Virginia Medical School
- Study start
- Jan 2017 (actual)
- Primary completion
- 19 Sep 2019 (actual)
- Study completion
- 19 Sep 2019 (actual)
- First posted
- 6 Apr 2016 (estimated)
- Results
- Posted 12 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Therapy | Active comparator | Drug: Oral Aztreonam, Drug: Nasal PlaceboOral 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 | Drug: Oral Aztreonam, Drug: Nasal AztreonamOral 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 |
Who may qualify
- Ages
- 7 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Males or females 7 years of age or older and able to perform pulmonary function testing
- Confirmed diagnosis of CF by the 1997 CF Consensus Conference criteria and followed by the VCU or EVMS CF clinic
- Presence of PA in 2 lower respiratory tract (sputum) cultures in the 24 months before screening
- Subjects and/or parent guardian must be able to give written informed consent prior to any study related procedure
- All sexually active female subjects who are of childbearing potential must agree to use an effective method of contraception (i.e.condoms or abstinence).
Key exclusion criteria (11 listed)
- Use of oral, IV or inhaled antibiotics within 0 days before study other than low dose azithromycin
- Severe pulmonary disease with FEV1<30% predicted of baseline SpO2<0.90
- ENT surgery within 6 months of screening
- Allergy or documented adverse reaction to aztreonam
- Epistaxis or significant (>30mL) hemoptysis in the past 6 months
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 |
|---|---|---|
| Oral AztreonamAlso: Cayston, AzactamStandard Therapy Comparator (Oral Cayston 75mg three times a day) | Drug | Standard Therapy, Study Therapy |
| Nasal AztreonamAlso: Cayston, AzactamStudy Therapy (nasal Aztreonam 75mg twice per day) | Drug | Study Therapy |
| Nasal PlaceboAlso: SalinePlacebo (nasal saline twice per day) | Drug | Standard Therapy |
Primary outcome
Number of Protocol-defined Pulmonary Exacerbations Treated With IV Anti-pseudomonal Antibiotics on Day 140
Time frame: 140 days
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.
8 secondary outcomes
Time to First Protocol-defined Pulmonary Exacerbation Treated With IV Anti-pseudomonal Antibiotics
Time frame: Up to 6 months
Change in Sinus and Nasal QoL Questionnaire (SNOT-20) on Day 140 and Day 168
Time frame: Day 140 and Day 168
Change in Cystic Fibrosis QoL Score (CFQ-R) on Day 140
Time frame: Day 140
Change in Pulmonary Function (FVC and FEV1 Percent Predicted) on Day 140
Time frame: Day 140
Change in Paired Sputum Cultures and Nasal Swabs for Bacteria and Antibiotic Resistance
Time frame: 1 year
Change in Acoustic Rhinometry for Nasal Obstruction (Volume) (Will be Measured at VCU Site ).
Time frame: 1 year
Number of Safety and Adverse Events Including Nasal Stuffiness, Epistaxis, and Headache.
Time frame: 1 year
Number of Protocol-defined Pulmonary Exacerbations Treated With Oral Anti-pseudomonal Antibiotics
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Individual participant data will be deidentified and will not be availalble.
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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.
Bruce K Rubin, MD principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oral Aztreonam and Nasal Aztreonam in people with Cystic Fibrosis, run by Virginia Commonwealth University at 1 site in United States.
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 8 inclusion and 11 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: stopped early, as of the sponsor's last update on 28 Jan 2021. 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 United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Protocol-defined Pulmonary Exacerbations Treated With IV Anti-pseudomonal Antibiotics on Day 140 (time frame: 140 days). 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 28 Jan 2021.