Idiopathic Pulmonary FibrosisNCT02173145
Azithromycin in Idiopathic Pulmonary Fibrosis
A study testing azithromycin in people with Idiopathic Pulmonary Fibrosis and Cough, run by Insel Gruppe AG, University Hospital Bern at 4 sites in Switzerland.
Trial summary
Idiopathic pulmonary fibrosis (IPF) is a devastating disease with no cure available. Patients suffer from respiratory symptoms including dyspnea and cough. To improve life quality the investigators will test the effects of immunomodulation of macrolides specifically on cough in IPF patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis, Cough
- What is being tested?
- azithromycin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 4 sitesSwitzerland
- Study dates
- 19 Aug 2014to 16 Aug 2019
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Idiopathic pulmonary fibrosis; new diagnosis, or known. Diagnosis according to the current guidelines from ATS/ERS for IPF diagnosis, other differential diagnoses ruled out.
- Clinical symptoms of cough
- Written informed consent for study participation
Who cannot join
- Previous history of an adverse reaction or allergy on azithromycin or other macrolide or ketolide antibiotics or any other ingredient (e.g. lactose)
- Evidence of respiratory infection or systemic infection one month before randomisation
- Known rhythmogenic heart disease
- Pregnancy or lactation
- History of non-compliance to medical treatment
- Current alcohol or drug abuse
Show all 16Show fewer
- Active hepatitis, history of hepatitis, other significant liver disease
- Serum bilirubin > 50 μmol/L
- Transaminases or alkaline phosphatase elevated > 3x upper limit of normal at baseline
- Severe renal insufficiency with GFR <10ml/min
- Concomitant treatment with ergotamines
- Concomitant treatment with ciclosporin
- Concomitant treatment with ributin
- Concomitant treatment with digoxin
- Change of medication until 4 weeks before randomisation
- Pirfenidone <3 Mo
Trial locations and contacts
4 sites in 1 country.
Switzerland4 sites
Universitätsspital Basel
Basel
University Hospital for Pulmonology
Bern, 3010
Kantonsspital St. Gallen
Sankt Gallen
Universitätsspital Zürich
Zurich
About this study
Official title: Azithromycin for the Treatment of Cough in Idiopathic Pulmonary Fibrosis- a Clinical Trial
Idiopathic pulmonary fibrosis (IPF) is a devastating disease with no cure available. Patients suffer from respiratory symptoms including dyspnea and cough. To improve life quality the investigators will test the effects of immunomodulation of macrolides specifically on cough in IPF patients. The investigators hypothesize that immunomodulatory treatment reduces cough frequency and might improve lung function.
Read the detailed description
Background
Idiopathic pulmonary fibrosis is a progressive interstitial lung disease, which ultimately leads to respiratory failure and death. The median survival is 2-3 years and thus comparable to the survival of a malignant disease. Today, there is no cure available. Improvement of quality of life (QoL) is thus a major goal in IPF patients. Cough is a common distressing and debilitating symptom in IPF. Increased cough in IPF patients may be linked to functional upregulation of lung sensory neurones. In addition, cough independently predicts disease progression in IPF patients. Symptomatic treatment options for cough in IPF are limited. Dysregulation of the immune system has been suggested to cause IPF associated cough and treatment trials with immunomodulating agents have been promising. Unfortunately the recently studied medication thalidomide is famous for its side effects and might be apprehensively received by some patients.
Immunomodulatory effects of macrolide treatment in chronic inflammatory diseases as well as reduced cough reflex in animal studies suggest a possible reduction in cough in IPF patients. In addition, in animal in vivo models azithromycin also showed anti-fibrotic properties.
The investigators hypothesize that immunomodulatory treatment of IPF patients with AZT reduces cough frequency and might improve lung function.
Objective
The purpose of this protocol is to determine the effect of azithromycin (AZT) on subjective and objective cough, QoL and lung function, its effects on biomarkers as well as its safety in patients with idiopathic pulmonary fibrosis.Specific Objectives
- To determine the efficiency after 12 weeks of treatment on subjective and objective cough reduction and increase of QoL
- To monitor safety by recording severe adverse events, including mortality, organ-specific toxicities and exacerbations requiring hospitalization
- To test efficiency at 12 weeks with overall response measured by changes in FEV1, FVC, TLC, DLCO, oxygen desaturation on exertion and 6-min walking distance
- To determine efficiency in clinical course
- To monitor overall adverse events
- To determine the influence on cytokines and biomarkers in IPF
- To determine the impact on oro-pharyngeal flora and antibiotical resistance
Methods
Single center, prospective, randomized, double blind, 2 treatments, 2 period crossover study with two 12-week treatment periods separated by a 4-week drug-free washout period and a 4 week follow-up period performed at the University Hospital Berne. All patients will be treated with both AZT and placebo. Individual changes in clinical symptoms with focus on cough frequency, life quality, lung function and adverse events will be monitored.
- Conditions
- Idiopathic Pulmonary Fibrosis, Cough
- Being tested
- azithromycin, placebo
- Keywords
- idiopathic pulmonary fibrosis, cough, immunomodulation, macrolide
- Medical subject headings
- Idiopathic Pulmonary Fibrosis, Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
azithromycinDrug
Azithromycin is a macrolide antibiotic. 500mg Azithromycin will be given p.o. 3 times a week for 3 months. Azithromycin will be compared to placebo.
placeboDrug
Placebo will be given 3 times a wek over a period of 3 months.
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin first, Placebo second | Active comparator | Medication with Azithromycin 500mg/d 3x/week p.o. o.d. for 12 weeks or placebo. Receives: Drug: azithromycin; Drug: placebo |
| Placebo first, Azithromycin second | Active comparator | Medication with Azithromycin 500mg/d 3x/week p.o. o.d. for 12 weeks or placebo. Placebo will be capsulated similar to verum and given 3 times a week. Receives: Drug: azithromycin; Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with a subjective response to treatment
Subjective response is defined as a 1.3 unit reduction of cough as measured with the Leicester Cough Score from treatment start to 12 weeks of treatment.
Measured: 3 months
Secondary outcomes (6)
Number of patients with an objective response to treatment
Objective response is defined as the Overall response in the measured cough frequency by respiratory Polygraph (Resmed, Nox T3®).
Measured: 3 months
Number of patients with a change in lung function
Measured by FEV1, FVC, TLC, \& DLCO
Measured: 3 months
Number of patients with a change in oxygen saturation
Measured by oxygen desaturation on exertion
Measured: 3 months
Number of patients with a change in quality of life
Measured by quality of life questionnaires
Measured: 3 months
Number of patients with changes in oropharyngeal flora
Measured: 3 months
Number of patients with a change in 6 min walking distance
Measured by oxygen desaturation on 6-min walking distance
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2014 (estimated)
- Study start19 Aug 2014
- Primary completion16 Aug 2019
- Study completion16 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bern
- Responsible party
- Sponsor
- Investigators
- Manuela Funke, MD, Principal investigator, University Hospital for Pulmonology, Berne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02173145
- Sponsor's protocol ID
- 002/14
- Status last verified
- Aug 2019
- First submitted
- 23 Jun 2014
- Last updated
- 28 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Guler SA, Clarenbach C, Brutsche M, Hostettler K, Brill AK, Schertel A, Geiser TK, Funke-Chambour M. Azithromycin for the Treatment of Chronic Cough in Idiopathic Pulmonary Fibrosis: A Randomized Controlled Crossover Trial. Ann Am Thorac Soc. 2021 Dec;18(12):2018-2026. doi: 10.1513/AnnalsATS.202103-266OC.
PubMed 34015241Rindlisbacher B, Schmid C, Geiser T, Bovet C, Funke-Chambour M. Serum metabolic profiling identified a distinct metabolic signature in patients with idiopathic pulmonary fibrosis - a potential biomarker role for LysoPC. Respir Res. 2018 Jan 10;19(1):7. doi: 10.1186/s12931-018-0714-2.
PubMed 29321022Rindlisbacher B, Strebel C, Guler S, Kollar A, Geiser T, Martin Fiedler G, Benedikt Leichtle A, Bovet C, Funke-Chambour M. Exhaled breath condensate as a potential biomarker tool for idiopathic pulmonary fibrosis-a pilot study. J Breath Res. 2017 Nov 29;12(1):016003. doi: 10.1088/1752-7163/aa840a.
PubMed 28775244
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Azithromycin for the Treatment of Cough in Idiopathic Pulmonary Fibrosis- a Clinical Trial
- ClinicalTrials.gov ID
- NCT02173145
- Acronym / sponsor ID
- 002/14
- Conditions
- Idiopathic Pulmonary Fibrosis, Cough
- Keywords
- idiopathic pulmonary fibrosis, cough, immunomodulation, macrolide
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- University of Bern
- Study start
- 19 Aug 2014 (actual)
- Primary completion
- 16 Aug 2019 (actual)
- Study completion
- 16 Aug 2019 (actual)
- First posted
- 24 Jun 2014 (estimated)
- 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.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease with no cure available. Patients suffer from respiratory symptoms including dyspnea and cough. To improve life quality the investigators will test the effects of immunomodulation of macrolides specifically on cough in IPF patients. The investigators hypothesize that immunomodulatory treatment reduces cough frequency and might improve lung function.
Detailed description
Background
Idiopathic pulmonary fibrosis is a progressive interstitial lung disease, which ultimately leads to respiratory failure and death. The median survival is 2-3 years and thus comparable to the survival of a malignant disease. Today, there is no cure available. Improvement of quality of life (QoL) is thus a major goal in IPF patients. Cough is a common distressing and debilitating symptom in IPF. Increased cough in IPF patients may be linked to functional upregulation of lung sensory neurones. In addition, cough independently predicts disease progression in IPF patients. Symptomatic treatment options for cough in IPF are limited. Dysregulation of the immune system has been suggested to cause IPF associated cough and treatment trials with immunomodulating agents have been promising. Unfortunately the recently studied medication thalidomide is famous for its side effects and might be apprehensively received by some patients.
Immunomodulatory effects of macrolide treatment in chronic inflammatory diseases as well as reduced cough reflex in animal studies suggest a possible reduction in cough in IPF patients. In addition, in animal in vivo models azithromycin also showed anti-fibrotic properties.
The investigators hypothesize that immunomodulatory treatment of IPF patients with AZT reduces cough frequency and might improve lung function.
Objective
The purpose of this protocol is to determine the effect of azithromycin (AZT) on subjective and objective cough, QoL and lung function, its effects on biomarkers as well as its safety in patients with idiopathic pulmonary fibrosis.Specific Objectives
- To determine the efficiency after 12 weeks of treatment on subjective and objective cough reduction and increase of QoL
- To monitor safety by recording severe adverse events, including mortality, organ-specific toxicities and exacerbations requiring hospitalization
- To test efficiency at 12 weeks with overall response measured by changes in FEV1, FVC, TLC, DLCO, oxygen desaturation on exertion and 6-min walking distance
- To determine efficiency in clinical course
- To monitor overall adverse events
- To determine the influence on cytokines and biomarkers in IPF
- To determine the impact on oro-pharyngeal flora and antibiotical resistance
Methods
Single center, prospective, randomized, double blind, 2 treatments, 2 period crossover study with two 12-week treatment periods separated by a 4-week drug-free washout period and a 4 week follow-up period performed at the University Hospital Berne. All patients will be treated with both AZT and placebo. Individual changes in clinical symptoms with focus on cough frequency, life quality, lung function and adverse events will be monitored.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azithromycin first, Placebo second | Active comparator | Drug: azithromycin, Drug: placeboMedication with Azithromycin 500mg/d 3x/week p.o. o.d. for 12 weeks or placebo. |
| Placebo first, Azithromycin second | Active comparator | Drug: azithromycin, Drug: placeboMedication with Azithromycin 500mg/d 3x/week p.o. o.d. for 12 weeks or placebo. Placebo will be capsulated similar to verum and given 3 times a week. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18 years
- Idiopathic pulmonary fibrosis; new diagnosis, or known. Diagnosis according to the current guidelines from ATS/ERS for IPF diagnosis, other differential diagnoses ruled out.
- Clinical symptoms of cough
- Written informed consent for study participation
Key exclusion criteria (16 listed)
- Previous history of an adverse reaction or allergy on azithromycin or other macrolide or ketolide antibiotics or any other ingredient (e.g. lactose)
- Evidence of respiratory infection or systemic infection one month before randomisation
- Known rhythmogenic heart disease
- Pregnancy or lactation
- History of non-compliance to medical treatment
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 is a macrolide antibiotic. 500mg Azithromycin will be given p.o. 3 times a week for 3 months. Azithromycin will be compared to placebo. | Drug | Azithromycin first, Placebo second, Placebo first, Azithromycin second |
| placeboPlacebo will be given 3 times a wek over a period of 3 months. | Drug | Azithromycin first, Placebo second, Placebo first, Azithromycin second |
Primary outcome
Number of patients with a subjective response to treatment
Time frame: 3 months
Subjective response is defined as a 1.3 unit reduction of cough as measured with the Leicester Cough Score from treatment start to 12 weeks of treatment.
6 secondary outcomes
Number of patients with an objective response to treatment
Time frame: 3 months
Number of patients with a change in lung function
Time frame: 3 months
Number of patients with a change in oxygen saturation
Time frame: 3 months
Number of patients with a change in quality of life
Time frame: 3 months
Number of patients with changes in oropharyngeal flora
Time frame: 3 months
Number of patients with a change in 6 min walking distance
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
- Derived from this study: PubMed 34015241Guler SA, Clarenbach C, Brutsche M, Hostettler K, Brill AK, Schertel A, Geiser TK, Funke-Chambour M. Azithromycin for the Treatment of Chronic Cough in Idiopathic Pulmonary Fibrosis: A Randomized Controlled Crossover Trial. Ann Am Thorac Soc. 2021 Dec;18(12):2018-2026. doi: 10.1513/AnnalsATS.202103-266OC.
- Derived from this study: PubMed 29321022Rindlisbacher B, Schmid C, Geiser T, Bovet C, Funke-Chambour M. Serum metabolic profiling identified a distinct metabolic signature in patients with idiopathic pulmonary fibrosis - a potential biomarker role for LysoPC. Respir Res. 2018 Jan 10;19(1):7. doi: 10.1186/s12931-018-0714-2.
- Derived from this study: PubMed 28775244Rindlisbacher B, Strebel C, Guler S, Kollar A, Geiser T, Martin Fiedler G, Benedikt Leichtle A, Bovet C, Funke-Chambour M. Exhaled breath condensate as a potential biomarker tool for idiopathic pulmonary fibrosis-a pilot study. J Breath Res. 2017 Nov 29;12(1):016003. doi: 10.1088/1752-7163/aa840a.
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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.
Manuela Funke, MD principal investigator
University Hospital for Pulmonology, Berne
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing azithromycin in people with Idiopathic Pulmonary Fibrosis and Cough, run by Insel Gruppe AG, University Hospital Bern at 4 sites in Switzerland.
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 4 inclusion and 16 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: finished, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Switzerland. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 patients with a subjective response to treatment (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02173145, which also lists 3 linked publications.
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 Aug 2019.