AsthmaPhase 4AZIMUNENCT04319705
Anti-viral Effects of Azithromycin in Patients With Asthma and COPD
A Phase 4 study testing Azithromycin in people with Asthma and COPD, run by Bispebjerg Hospital at 1 site in Denmark.
Trial summary
The purpose of this study is to investigate the anti-viral effects of low-dose AZM treatment in patients with asthma and COPD with an exacerbation history. The investigators expect that long-term treatment with low dose AZM modulates the immune response to viral infections, with an increased interferon release, in… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma, COPD, Exacerbation Copd
- What is being tested?
- Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteDenmark
- Study dates
- 2 Mar 2020to 31 Dec 2022
- Phase
- Phase 4
- 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 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Asthma patients (n=40)
- Diagnosis of asthma according to GINA, with confirmed variable airflow obstruction at screening visit or previously.
- Age ≥ 18 through 75 years.
- A postbronchodilator FEV1 ≥ 50% predicted
- Maintenance treatment with ICS and ≥ 1 second controller (LABA, LAMA, LTRA or Xanthines) for at least three months prior to Visit 1.
- Non-smokers (<10 packyears, quit >6 months).
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- ≥ 1 Systemic steroid treated exacerbation in the past one year despite maintenance treatment with inhaled corticosteroids.
- Eosinophilic (n=20, blood eosinophils ≥ 0.200x109/L) and non-eosinophilic (n=20, blood eosinophils <0.200x109/L) phenotypes.
- COPD patients (n=40)
- Diagnosis of COPD according to GOLD
- Age ≥ 45 through 75 years.
- ≥ 10 packyears smoking history (current or ex-smokers).
- A postbronchodilator FEV1 ≥ 30% predicted.
- Maintenance treatment with long-acting bronchodilators (LABA and/or LAMA) ≥ ICS.
- ≥ 1 Systemic steroid and/or antibiotic treated exacerbation in the past one year.
- Eosinophilic (n=20, blood eosinophils ≥0.200x109/L) and non-eosinophilic (n=20, blood eosinophils <0.200x109/L) phenotypes.
- Healthy controls (n=20)
- Asymptomatic
- Non-smoking (<10 packyears, quit >6 months)
- Normal spirometry (FEV1, FVC, FEV1/FVC ratio: all >LLN)
- FeNO < 25 ppb
- Non-atopic based on skin-prick test
- Negative mannitol provocation test
- Younger (n=10, 18-45 years) and older (n=10, >45-75 years) subjects.
Who cannot join
- Any of the following would exclude the subject from participation in the study:
- Previous medical history or evidence of an uncontrolled intercurrent illness that in the opinion of the investigator may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject's ability to participate in the study. Subjects with well-controlled comorbid disease (e.g., hypertension, hyperlipidemia, gastroesophageal reflux disease) on a stable treatment regimen for 15 days prior to Visit 1 are eligible.
- Any concomitant respiratory disease that in the opinion of the investigator and/or medical monitor will interfere with the evaluation of the investigational product or interpretation of subject safety or study results (e.g., cystic fibrosis, pulmonary fibrosis, moderate-severe bronchiectasis, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, active tuberculosis). In addition for the different groups the following:
- Patient with asthma: concomitant COPD.
- Patients with COPD: concomitant asthma (former and current)
- Healthy subjects: COPD and asthma.
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- Any clinically relevant abnormal findings in hematology or clinical chemistry (laboratory results from Visit 1), physical examination, vital signs during the screening, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject's ability to participate in the study.
- Evidence of active liver disease, including jaundice or aspartate transaminase, alanine transaminase, or alkaline phosphatase >1.5 times the upper limit of normal (laboratory results from Visit 1).
- GFR <30 ml/min.
- Acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 2 weeks prior to Visit 1, during the run-in period, or at Visit 2 (randomization).
- A positive human immunodeficiency virus (HIV) test at screening or subject taking antiretroviral medications, as determined by medical history and/or subject's verbal report.
- History of sensitivity to any component of the investigational product formulation or a history of drug or other allergy that, in the opinion of the investigator or medical monitor contraindicates their participation.
- History of any known primary immunodeficiency disorder excluding asymptomatic selective immunoglobulin A or IgG subclass deficiency.
- Receipt of any of the following within 30 days prior to Visit 1:
- Immunoglobulin or blood products, or
- Receipt of any investigational non-biologic agent within 30 days or 5 half-lives prior Visit 1, whichever is longer.
- Pregnant, breastfeeding or lactating females
- History of chronic alcohol or drug abuse within 12 months prior to Visit 1.
- Planned surgical procedures requiring general anesthesia or in-patient status for > 1 day during the conduct of the study.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Concurrent enrollment in another clinical study involving an investigational treatment.
- Receipt of any live or attenuated vaccines within 15 days prior to Visit 1.
- Long QTc interval on ECG (QTc >480msec).
- History of the following cardiac comorbidities:
- Life-threatening arrhythmias
- Myocardial infarction (NSTEMI or STEMI) less than 6 months before start of the study
- Unstable angina
- History of severe heart failure
- Documented severe hypokalemia (K <3.0 mmol/L) or hypomagnesemia (Mg <0.5 mmol/L).
- Life expectancy <6 months.
- Hearing impairment.
- Oxygen saturation <92% at room air, patients on LTOT, history of chronic respiratory failure (hypercapnia).
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
University Hospital Bispebjerg and Frederiksberg
Copenhagen, 2400
Muzhda Ghanizada, MD, +45 29 20 48 43, muzhdaghanizada@hotmail.com
Therese S Lapperre, MD, PhD, +45 27597822, therese.sophie.lapperre@regionh.dk
About this study
Official title: Effects of Azithromycin Treatment on Anti-viral Immunity in Patients With Asthma and COPD - A Randomized Double-blind, Placebo-controlled Trial
The purpose of this study is to investigate the anti-viral effects of low-dose AZM treatment in patients with asthma and COPD with an exacerbation history.
The investigators expect that long-term treatment with low dose AZM modulates the immune response to viral infections, with an increased interferon release, in patients with asthma and COPD with an exacerbation history. In addition, the investigators expect a decrease in inflammatory cells and mediators, and changes in bacteria, measured in samples from the lungs.
Half of the participants will receive azithromycin on top of their regular asthma/COPD treatment, while the other half will receive placebo on top of their regular asthma/COPD treatment.
Read the detailed description
Asthma and COPD are responsible for considerable global morbidity and healthcare costs, primarily driven by exacerbations, i.e. acute flare-ups. Hence there is a clear need for better interventions preventing exacerbations. A majority of exacerbations are driven by infections, and in particular viral infections. Importantly, the anti-viral defense in asthma and COPD seems compromised, with a relative inability to combat infections, but also a disproportionate inflammatory response to infections, i.e. an increased immunoreactivity involving release of epithelial 'alarmins', such as IL-33 and thymic stromal lymphopoietin (TSLP).
Long-term low dose macrolides have been shown to reduce exacerbations in both diseases and are increasingly used clinically, but the mechanism of action is unknown. Macrolides have anti-viral properties in vitro, however their anti-viral properties have not been established in patients with asthma and COPD during exacerbations.
The purpose of this study is to investigate the anti-viral and anti-inflammatory effects in the airways, as well as the effects of azithromycin on the lung microbiome. In order to study these effects, the key endpoints in this trial will need to be obtained from bronchoscopic sampling of bronchial brushes, bronchial biopsies and BAL. But performing bronchoscopies during acute exacerbations, when patients are infected with respiratory viruses, is difficult in view of safety. Therefore, this study on in vitro rhinovirus responses of human bronchial epithelial cells before and after in vivo treatment with macrolides represents a novel model to study treatment effects on immunoreactivity during exacerbations.
The investigators hypothesize that long-term treatment with low dose AZM modulates the immune response to viral infections, with an increased interferon release, in patients with asthma and COPD with an exacerbation history.
The investigators also speculate that AZM treatment leads to a decreased release of the epithelial alarmins (e.g. IL-33 and TSLP) in response to viral infection, in patients with asthma and COPD with an exacerbation history.
Furthermore, treatment effects of low dose AZM on functional and compositional changes of bacterial communities of the respiratory- and gastrointestinal tract, and their association with changes in immunoreactivity will be studied.
This trial offers the opportunity to study potential biomarkers and surrogate endpoints, but also to identify the anti-inflammatory effects of azithromycin on a mechanistic level.
This study is a randomized, double-blind, placebo-controlled trial. It includes a enrolment period of maximum 4 weeks, with a bronchoscopy before and after 12 weeks of treatment (500mg azithromycin or placebo, 3 times per week).
- Conditions
- Asthma, COPD, Exacerbation Copd, Asthma; Eosinophilic, Bronchial Diseases, Lung Diseases, Obstructive
- Being tested
- Azithromycin, Placebo oral tablet
- Keywords
- Eosinophil, Smoking, COPD, Asthma, Rhinovirus, Azithromycin, Inflammation, Microbiome
- Medical subject headings
- Asthma, Pulmonary Disease, Chronic Obstructive, Pulmonary Eosinophilia, Bronchial Diseases, Lung Diseases, Obstructive, Lung Diseases, Immune System Diseases, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
Azithromycin, 500mg, 3 times per week, 12-week treatment period, administered orally
Placebo oral tabletDrug
capsule containing placebo, 3 times per week, 12-week treatment period, administered orally
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin | Experimental | Azithromycin, 500mg capsule, 3 times per week, during a 12-week period, administered orally Receives: Drug: Azithromycin |
| Placebo | Placebo comparator | Apart from the active substance, the placebo is otherwise identical to IMP, capsule, 3 times per week, during a 12-week period, administered orally Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
IFN-beta gene and/or protein expression
To investigate the potential change in viral induced interferon response in HBECs from baseline and after 12 weeks of treatment with low dose azithromycin or placebo, after stimulation with viral infection mimics (RV16 or Poly (I:C)
Measured: 12 weeks
Viral load
To investigate the potential change in viral load response in HBECs from baseline and 12 weeks of treatment with low dose azithromycin or placebo, after stimulation with viral infection mimics (RV16 or Poly (I:C)
Measured: 12 weeks
Secondary outcomes (5)
INF-beta gene and/or protein expression
To investigate the potential change in viral induced interferon response in HBECs from baseline and after 12 weeks of treatment with low dose azithromycin or placebo, after stimulation with a combination of: viral infection mimics (RV16 or Poly (I:C) +/- allergens (e.g. HDM), +/- scratching of epithelium, +/- smoke exposure.
Measured: 12 weeks
IL-33
To investigate the potential change in IL-33 response in HBECs from baseline and after 12 weeks of treatment with low dose azithromycin or placebo, after stimulation with viral infection mimics (RV16 or Poly (I:C) in eosinophilic (blood eosinophils >0.2x109/L) and non-eosinophilic (blood eosinophils <0.2x109/L) patients with asthma and COPD.
Measured: 12 weeks
TSLP
To investigate the potential change in IL-33 response in HBECs from baseline and after 12 weeks of treatment with low dose azithromycin or placebo, after stimulation with viral infection mimics (RV16 or Poly (I:C) in eosinophilic (blood eosinophils >0.2x109/L) and non-eosinophilic (blood eosinophils <0.2x109/L) patients with asthma and COPD.
Measured: 12 weeks
Mast cells, eosinophils, Neutrophils
To evaluate the potential change in histologic phenotypes in bronchial biopsies from baseline and after 12 weeks of treatment with low dose azithromycin.
Measured: 12 weeks
Lung microbiome
To evaluate the potential changes in microbiome abundance in BAL-fluid from baseline and after 12 weeks of treatment with low dose azithromycin measured by 16S gene sequencing.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2020
- Study start2 Mar 2020
- Primary completion31 Mar 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bispebjerg Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Lund University, University of Copenhagen, Herlev and Gentofte Hospital
- Responsible party
- Principal investigator, Celeste Porsbjerg, Bispebjerg Hospital
- Investigators
- Celeste Porsbjerg, MD, PhD, Principal investigator, University Hospital Bispebjerg and FrederiksbergTherese S Lapperre, MD, PhD, Study director, University Hospital Bispebjerg and Frederiksberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04319705
- Sponsor's protocol ID
- 0052256
- Acronym
- AZIMUNE
- Status last verified
- Jul 2021
- First submitted
- 12 Mar 2020
- Last updated
- 26 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- 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 26 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Azithromycin Treatment on Anti-viral Immunity in Patients With Asthma and COPD - A Randomized Double-blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT04319705
- Acronym / sponsor ID
- AZIMUNE / 0052256
- Conditions
- Asthma, COPD, Exacerbation Copd, Asthma; Eosinophilic, Bronchial Diseases, Lung Diseases, Obstructive
- Keywords
- Eosinophil, Smoking, COPD, Asthma, Rhinovirus, Azithromycin, Inflammation, Microbiome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Bispebjerg HospitalUniversity, hospital or other
- Collaborators
- Lund University, University of Copenhagen, Herlev and Gentofte Hospital
- Study start
- 2 Mar 2020 (actual)
- Primary completion
- 31 Mar 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 24 Mar 2020 (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.
The purpose of this study is to investigate the anti-viral effects of low-dose AZM treatment in patients with asthma and COPD with an exacerbation history.
The investigators expect that long-term treatment with low dose AZM modulates the immune response to viral infections, with an increased interferon release, in patients with asthma and COPD with an exacerbation history. In addition, the investigators expect a decrease in inflammatory cells and mediators, and changes in bacteria, measured in samples from the lungs.
Half of the participants will receive azithromycin on top of their regular asthma/COPD treatment, while the other half will receive placebo on top of their regular asthma/COPD treatment.
Detailed description
Asthma and COPD are responsible for considerable global morbidity and healthcare costs, primarily driven by exacerbations, i.e. acute flare-ups. Hence there is a clear need for better interventions preventing exacerbations. A majority of exacerbations are driven by infections, and in particular viral infections. Importantly, the anti-viral defense in asthma and COPD seems compromised, with a relative inability to combat infections, but also a disproportionate inflammatory response to infections, i.e. an increased immunoreactivity involving release of epithelial 'alarmins', such as IL-33 and thymic stromal lymphopoietin (TSLP).
Long-term low dose macrolides have been shown to reduce exacerbations in both diseases and are increasingly used clinically, but the mechanism of action is unknown. Macrolides have anti-viral properties in vitro, however their anti-viral properties have not been established in patients with asthma and COPD during exacerbations.
The purpose of this study is to investigate the anti-viral and anti-inflammatory effects in the airways, as well as the effects of azithromycin on the lung microbiome. In order to study these effects, the key endpoints in this trial will need to be obtained from bronchoscopic sampling of bronchial brushes, bronchial biopsies and BAL. But performing bronchoscopies during acute exacerbations, when patients are infected with respiratory viruses, is difficult in view of safety. Therefore, this study on in vitro rhinovirus responses of human bronchial epithelial cells before and after in vivo treatment with macrolides represents a novel model to study treatment effects on immunoreactivity during exacerbations.
The investigators hypothesize that long-term treatment with low dose AZM modulates the immune response to viral infections, with an increased interferon release, in patients with asthma and COPD with an exacerbation history.
The investigators also speculate that AZM treatment leads to a decreased release of the epithelial alarmins (e.g. IL-33 and TSLP) in response to viral infection, in patients with asthma and COPD with an exacerbation history.
Furthermore, treatment effects of low dose AZM on functional and compositional changes of bacterial communities of the respiratory- and gastrointestinal tract, and their association with changes in immunoreactivity will be studied.
This trial offers the opportunity to study potential biomarkers and surrogate endpoints, but also to identify the anti-inflammatory effects of azithromycin on a mechanistic level.
This study is a randomized, double-blind, placebo-controlled trial. It includes a enrolment period of maximum 4 weeks, with a bronchoscopy before and after 12 weeks of treatment (500mg azithromycin or placebo, 3 times per week).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azithromycin | Experimental | Drug: AzithromycinAzithromycin, 500mg capsule, 3 times per week, during a 12-week period, administered orally |
| Placebo | Placebo comparator | Drug: Placebo oral tabletApart from the active substance, the placebo is otherwise identical to IMP, capsule, 3 times per week, during a 12-week period, administered orally |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Asthma patients (n=40)
- COPD patients (n=40)
- Healthy controls (n=20)
Key exclusion criteria (32 listed)
- Any of the following would exclude the subject from participation in the study:
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 |
|---|---|---|
| AzithromycinAzithromycin, 500mg, 3 times per week, 12-week treatment period, administered orally | Drug | Azithromycin |
| Placebo oral tabletcapsule containing placebo, 3 times per week, 12-week treatment period, administered orally | Drug | Placebo |
Primary outcome
IFN-beta gene and/or protein expression
Time frame: 12 weeks
To investigate the potential change in viral induced interferon response in HBECs from baseline and after 12 weeks of treatment with low dose azithromycin or placebo, after stimulation with viral infection mimics (RV16 or Poly (I:C)
Viral load
Time frame: 12 weeks
To investigate the potential change in viral load response in HBECs from baseline and 12 weeks of treatment with low dose azithromycin or placebo, after stimulation with viral infection mimics (RV16 or Poly (I:C)
5 secondary outcomes
INF-beta gene and/or protein expression
Time frame: 12 weeks
IL-33
Time frame: 12 weeks
TSLP
Time frame: 12 weeks
Mast cells, eosinophils, Neutrophils
Time frame: 12 weeks
Lung microbiome
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2021.
- Individual participant dataSharing planned: No
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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.
Celeste Porsbjerg, MD, PhD principal investigator
University Hospital Bispebjerg and Frederiksberg
Therese S Lapperre, MD, PhD study director
University Hospital Bispebjerg and Frederiksberg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azithromycin in people with Asthma and COPD, run by Bispebjerg Hospital at 1 site in Denmark.
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 24 inclusion and 32 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 26 Jul 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 Denmark. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Muzhda Ghanizada, MD (+45 29 20 48 43, muzhdaghanizada@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IFN-beta gene and/or protein expression (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 26 Jul 2021.