Chronic CoughPhase 3AZCCNCT02196493
An Open Label Trial of Azithromycin in Chronic Productive Cough
A Phase 3 study testing Azithromycin in people with Chronic Cough, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
We have noticed a group of patients presenting with a longstanding wet cough which has often been treated as asthma. The cough is productive of sputum which frequently contains bacteria, but does not resolve with standard antibiotic treatment. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Cough
- What is being tested?
- Azithromycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2013to Dec 2016
- Phase
- Phase 3
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 and over
- Male or female
- Non-smokers for 10 years and <20 pack year equivalents in total
- Persistent productive cough for > 3 months in duration
- Use of effective contraception Acceptable contraceptive methods include: established use of oral, injected or implanted hormonal methods; placement of an intrauterine device (IUD) or intrauterine system (IUS); condom or occlusive cap (diaphragm or cervical/vault caps) with spermicide; true abstinence (when this is in line with the preferred and usual lifestyle of the participant); or vasectomised partner.
Who cannot join
- History of obvious inhaled irritant exposure
- Evidence of primary or secondary immunodeficiency.
- Clinically important bronchiectasis on HRCT scan
- Prolonged QT interval on ECG or significant cardiac pathology prior to commencing azithromycin
- Abnormal LFT's (greater than 2x upper limit of normal)
- Hypersensitivity to azithromycin or any macrolide/ketolide antibiotic
- Pregnancy or intent to become pregnant during course of study
- Contra-indication to bronchoscopy (as per British Thoracic Society Guidelines)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Respiratory Research Unit
Nottingham, Nottinghamshire, NG5 1PB
Matthew Martin, MBChB, 01158231935
Tim Harrison, MD, FRCP
About this study
We have noticed a group of patients presenting with a longstanding wet cough which has often been treated as asthma. The cough is productive of sputum which frequently contains bacteria, but does not resolve with standard antibiotic treatment.
A very similar cough is seen in subjects who smoke, have exposure to airbourne dusts or chemicals or have a condition known as bronchiectasis, but these problems have already been excluded.
Read more
We have found that prolonged treatment with an antibiotic called azithromycin is very effective but using azithromycin in this way is not licensed and there is currently no trial evidence to support its use.
This research will evaluate the clinical benefit of low dose azithromycin to determine if this is an effective and safe treatment for these patients. It will also involve a detailed investigation of these patients to determine whether they have enough in common to believe we are describing a new condition.
Read the detailed description
We and others have observed a cohort of patients, mainly referred with either poorly controlled asthma despite high dose treatment or suspected bronchiectasis, who give a history of chronic (often 3 months or more) productive cough which improves with antibiotic treatment but quickly relapses. Most deny wheeze and on examination there are often transmitted sounds from mucus in the large airways but no expiratory wheeze typical of asthma. Investigations including spirometry, bronchial challenges, chest X-ray, screen for immunodeficiency and high resolution CT (HRCT) scan exclude recognised causes of productive cough but sputum culture is often positive for Haemophilus influenzae although sometimes demonstrates normal respiratory flora despite being markedly purulent.
Due to their efficacy in cystic fibrosis and bronchiectasis we have empirically tried treatment with low dose macrolide antibiotics over 3-6 months often with dramatic benefit. This is however an unproven and unlicensed indication which needs to be more thoroughly evaluated.
The key objective of the study is to determine if 12 weeks treatment of patients with chronic productive cough with low dose azithromycin is both effective and safe.
The secondary objectives of the study are to describe the clinical and pathological features of a cohort of patients who present with chronic productive cough (with no evidence of bronchiectasis, smoking-related chronic bronchitis or immunodeficiency) to determine if these are sufficiently similar to justify a new diagnostic label.
- Conditions
- Chronic Cough
- Being tested
- Azithromycin
- Keywords
- Productive, Cough, Bronchitis, Azithromycin
- Medical subject headings
- Chronic Cough, Cough, Bronchitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
Also called Zithromax
250mg azithromycin three times per week for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin | Experimental | 250mg azithromycin three times weekly for 12 weeks Receives: Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in cough on the Leicester Cough Questionnaire (LCQ) score at week 12
Measured: 12 weeks after treatment started
Secondary outcomes (4)
Change from baseline in sputum colour (as per previously validated commercially available graded sputum colour chart) at week 12
Measured: 12 weeks after treatment started
Change from baseline in exhaled nitric oxide level (ppm) at week 24
Measured: 12 weeks after treatment started
Change from baseline in FEV1 (ml) at week 24
Measured: 12 weeks after treatment started
Change from baseline in sputum volume (ml) at week 12
Measured: 12 weeks after treatment started
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2014 (estimated)
- Study startDec 2013
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic CoughStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tim Harrison, MD, FRCP, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02196493
- Sponsor's protocol ID
- 13031
- Other IDs
- 2013-002938-20
- Acronym
- AZCC
- Status last verified
- Feb 2016
- First submitted
- 10 Jul 2014
- Last updated
- 18 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Martin MJ, Lee H, Clayton C, Pointon K, Soomro I, Shaw DE, Harrison TW. Idiopathic chronic productive cough and response to open-label macrolide therapy: An observational study. Respirology. 2019 Jun;24(6):558-565. doi: 10.1111/resp.13483. Epub 2019 Feb 5.
PubMed 30722097
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Trial of Azithromycin in Chronic Productive Cough
- ClinicalTrials.gov ID
- NCT02196493
- Acronym / sponsor ID
- AZCC / 13031
- Conditions
- Chronic Cough
- Keywords
- Productive, Cough, Bronchitis, Azithromycin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- Dec 2013
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 22 Jul 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.
We have noticed a group of patients presenting with a longstanding wet cough which has often been treated as asthma. The cough is productive of sputum which frequently contains bacteria, but does not resolve with standard antibiotic treatment.
A very similar cough is seen in subjects who smoke, have exposure to airbourne dusts or chemicals or have a condition known as bronchiectasis, but these problems have already been excluded.
We have found that prolonged treatment with an antibiotic called azithromycin is very effective but using azithromycin in this way is not licensed and there is currently no trial evidence to support its use.
This research will evaluate the clinical benefit of low dose azithromycin to determine if this is an effective and safe treatment for these patients. It will also involve a detailed investigation of these patients to determine whether they have enough in common to believe we are describing a new condition.
Detailed description
We and others have observed a cohort of patients, mainly referred with either poorly controlled asthma despite high dose treatment or suspected bronchiectasis, who give a history of chronic (often 3 months or more) productive cough which improves with antibiotic treatment but quickly relapses. Most deny wheeze and on examination there are often transmitted sounds from mucus in the large airways but no expiratory wheeze typical of asthma. Investigations including spirometry, bronchial challenges, chest X-ray, screen for immunodeficiency and high resolution CT (HRCT) scan exclude recognised causes of productive cough but sputum culture is often positive for Haemophilus influenzae although sometimes demonstrates normal respiratory flora despite being markedly purulent.
Due to their efficacy in cystic fibrosis and bronchiectasis we have empirically tried treatment with low dose macrolide antibiotics over 3-6 months often with dramatic benefit. This is however an unproven and unlicensed indication which needs to be more thoroughly evaluated.
The key objective of the study is to determine if 12 weeks treatment of patients with chronic productive cough with low dose azithromycin is both effective and safe.
The secondary objectives of the study are to describe the clinical and pathological features of a cohort of patients who present with chronic productive cough (with no evidence of bronchiectasis, smoking-related chronic bronchitis or immunodeficiency) to determine if these are sufficiently similar to justify a new diagnostic label.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azithromycin | Experimental | Drug: Azithromycin250mg azithromycin three times weekly for 12 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 and over
- Male or female
- Non-smokers for 10 years and <20 pack year equivalents in total
- Persistent productive cough for > 3 months in duration
- Use of effective contraception Acceptable contraceptive methods include: established use of oral, injected or implanted hormonal methods; placement of an intrauterine device (IUD) or intrauterine system (IUS); condom or occlusive cap (diaphragm or cervical/vault caps) with spermicide; true abstinence (when this is in line with the preferred and usual lifestyle of the participant); or vasectomised partner.
Key exclusion criteria (8 listed)
- History of obvious inhaled irritant exposure
- Evidence of primary or secondary immunodeficiency.
- Clinically important bronchiectasis on HRCT scan
- Prolonged QT interval on ECG or significant cardiac pathology prior to commencing azithromycin
- Abnormal LFT's (greater than 2x upper limit of normal)
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 |
|---|---|---|
| AzithromycinAlso: Zithromax250mg azithromycin three times per week for 12 weeks | Drug | Azithromycin |
Primary outcome
Change from baseline in cough on the Leicester Cough Questionnaire (LCQ) score at week 12
Time frame: 12 weeks after treatment started
4 secondary outcomes
Change from baseline in sputum colour (as per previously validated commercially available graded sputum colour chart) at week 12
Time frame: 12 weeks after treatment started
Change from baseline in exhaled nitric oxide level (ppm) at week 24
Time frame: 12 weeks after treatment started
Change from baseline in FEV1 (ml) at week 24
Time frame: 12 weeks after treatment started
Change from baseline in sputum volume (ml) at week 12
Time frame: 12 weeks after treatment started
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2016.
- Derived from this study: PubMed 30722097Martin MJ, Lee H, Clayton C, Pointon K, Soomro I, Shaw DE, Harrison TW. Idiopathic chronic productive cough and response to open-label macrolide therapy: An observational study. Respirology. 2019 Jun;24(6):558-565. doi: 10.1111/resp.13483. Epub 2019 Feb 5.
- 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.
Tim Harrison, MD, FRCP principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azithromycin in people with Chronic Cough, run by University of Nottingham at 1 site in United Kingdom.
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 5 inclusion and 8 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 18 Feb 2016. 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 Kingdom. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Matthew Martin, MBChB (01158231935, matthew.martin@nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in cough on the Leicester Cough Questionnaire (LCQ) score at week 12 (time frame: 12 weeks after treatment started). 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 NCT02196493, which also lists 1 linked publication.
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 18 Feb 2016.