BronchiectasisNCT04215172
Macrolides in COPD- Bronchiectasis Overlap
An observational study of Bronchiectasis, run by Assiut University.
Trial summary
To assess safety of long-term macrolide therapy in patients with COPD-bronchiectasis overlap syndrome And evaluate its efficacy in treating COPD-bronchiectasis overlap syndrome regarding change in clinical, functional and microbiological profile. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Bronchiectasis
- What is being tested?
- Macrolides
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2020to 1 Jul 2022
- Phase
- Observational
- 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
Study population: patients who are admittted toChest department of Assiut University Hospitals or visit its outpatients' clinic
Who may be able to join
- Aged 18 years or above, male or female.
- Non / Ex-smokers.
- Confirmed diagnosis of bronchiectasis based on high-resolution computed tomography scan.
- Confirmed diagnosis of COPD based on pulmonary function test.
Who cannot join
- Active smokers.
- Moderate to severe liver impairment (Child-Pugh B or C) and/or sever renal impairment (c. clearance less than 30ml/min).
- Patients who are known to be hypersensitive to macrolide.
- Patient with known or susceptible to have rhythm problems
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Safety and Efficacy of Long-Term Macrolide Therapy in Patients With COPD-Bronchiectasis Overlap Syndrome
To assess safety of long-term macrolide therapy in patients with COPD-bronchiectasis overlap syndrome And evaluate its efficacy in treating COPD-bronchiectasis overlap syndrome regarding change in clinical, functional and microbiological profile.
To define the, clinical, radiological, functional and microbiological patterns of patients with COPD-bronchiectasis overlap syndrome
Read the detailed description
COPD and bronchiectasis share common symptoms of cough with sputum production and susceptibility to recurrent exacerbations driven by new or persistent infection The overlap between chronic obstructive pulmonary disease (COPD) and bronchiectasis is a neglected area of research, and it is not covered by guidelines for clinical practice COPD is diagnosed on the basis of poorly reversible airflow obstruction and is therefore a physiological diagnosis. It is defined when an objective measure of airflow obstruction is associated with an abnormal inflammatory response of the lung to noxious stimuli, with cigarette smoke being the most common exposure in the developed world. Operationally, this implies that patients with any sufficient exposure and fixed airflow obstruction are labelled as having COPD.
Bronchiectasis is diagnosed in the presence of airway dilatation and airway wall thickening on imaging (usually computed tomography (CT)), and is therefore a structural diagnosis. Clinically significant disease is present when imaging abnormalities are associated with symptoms of persistent or recurrent bronchial infection.
in the 2014 Global initiative for chronic Obstructive Lung Disease guidelines, bronchiectasis was for the first time defined as a comorbidity of chronic obstructive pulmonary disease (COPD), and this change has been retained in the 2015 update, which emphasizes the influence of bronchiectasis in the natural history of COPD.
The prevalence of bronchiectasis in patients with COPD is high, especially in advanced stages. The identification of bronchiectasis in COPD has been defined as a different clinical COPD phenotype with greater symptomatic severity, more frequent chronic bronchial infection and exacerbations, and poor prognosis.
A recent meta-analysis by Du et al, of 5,329 COPD patients found a greatly increased exacerbation risk due to comorbid COPD with bronchiectasis compared to COPD alone.18 Moreover, the risk of exacerbations rose almost two times higher, colonization of the lungs four times higher, severe airway obstruction 30 percent higher, and mortality two times higher. It is not surprising that such elevated risks are also associated with higher healthcare costs.
Treatments useful in COPD may not be widely effective in bronchiectasis and vice versa. Inhaled corticosteroids provide perhaps the best example of this: they are widely used in COPD but not recommended for most patients with bronchiectasis . The reasons for this are unclear but probably reflect, in part, the diverse aetiology underlying bronchiectasis. In contrast, inhaled antibiotics, including antipseudomonal agents in appropriate patients, are of benefit and appear in current bronchiectasis guidelines ,but are not used routinely in stable COPD Macrolides, in addition to their antimicrobial effects, have decreased neutrophil chemotaxis and infiltration into the respiratory epithelium, inhibition of transcription factors leading to decreased proinflammatory cytokine production, down-regulation of adhesion molecule expression, inhibition of microbial virulence factors including biofilm formation, reduced generation of oxygen-free radicals, enhanced neutrophil apoptosis, and decreased mucus hypersecretion with improved mucociliary clearance.
- Conditions
- Bronchiectasis
- Being tested
- Macrolides
- Medical subject headings
- Bronchiectasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MacrolidesDrug
administration of azithromycin three times weekly for six months
| Study group | Role | What they receive |
|---|---|---|
| macrolides group | Every patient of this group will be educated and instructed about usage, dosing and side effects of the drug.
Dose: azithromycin 500 mg three times weekly for 6 months. added to the conventional treatment. Receives: Drug: Macrolides | |
| conventional group | Every patient of this group will receive the conventional treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
long-term macrolides therapy in patients with COPD-bronchiectasis overlap syndrome regarding ototoxicity, hepatotoxicity and cardiac toxicity
1)-ototoxicity by whispered- voice test before starting treatment and monthly The examiner stands arm's length (0.6 m) behind the seated patient and whispers a combination of numbers and letters (for example, 4-K-2) and then asks the patient to repeat the sequence.
If the patient responds correctly, hearing is considered normal; if the patient responds incorrectly, the test is repeated using a different number/letter combination The examiner always stands behind the patient to prevent lip reading The other ear is assessed similarly with a different combination of numbers and letters
-2)-assessment of hepatotoxicity by measuring liver enzymes (aspartate transaminase AST, Alanine transaminase ALT (Unit/Liter)) before starting treatment and monthly.
3)-assessment of possible prolongation of QT interval (millimeters) by ECG (electrocardiogram) before starting treatment and monthly.
Measured: two years
evaluate macrolides in treating COPD-bronchiectasis overlap syndrome regarding improvement of symptoms, frequency of exacerbations, systemic inflammatory response and pulmonary function tests.
- symptoms:
- Dyspnea score by mMRC (modified medical research council) score, with strenuous exercise 0 when hurrying or walking up a slight hill +1 Walks slower than people of the same age because of dyspnea +2 Stops for breath after walking 100 yards +3 Too dyspneic to leave house +4
- sputum volume by (milliliter),
- bronchiectasis health questionnaire (BHS)
- exacerbation: Frequency of outpatient visits per month and hospital admission if happened (number\month).
- systemic inflammation:
- CBC (complete blood count) (White Blood Cells(n/ microliter), differential count (%)
- Erythrocyte Sedimentation Rate (millimeter/hour)
- C-Reactive Protein (milligram\ liter)
- Microbiological:
Change in microbiological picture based on sputum culture and sensitivity
- Functional: Change in FEV1 (forced expiratory volume at one second) (liter/second.) all these will be done before starting treatment and monthly.
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2020
- Study start1 Aug 2020 (estimated)
- Primary completion1 Jan 2022 (estimated)
- Study completion1 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for BronchiectasisStudies of the same condition, open and under way.
- More trials run by Assiut 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alaa Sayed Ali, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04215172
- Sponsor's protocol ID
- COPD_bronchiactasis
- Status last verified
- Jul 2020
- First submitted
- 18 Dec 2019
- Last updated
- 22 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Hurst JR, Elborn JS, De Soyza A; BRONCH-UK Consortium. COPD-bronchiectasis overlap syndrome. Eur Respir J. 2015 Feb;45(2):310-3. doi: 10.1183/09031936.00170014. No abstract available.
PubMed 25653262Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58. doi: 10.1136/thx.2010.136119.
PubMed 20627931Martinez-Garcia MA, Miravitlles M. Bronchiectasis in COPD patients: more than a comorbidity? Int J Chron Obstruct Pulmon Dis. 2017 May 11;12:1401-1411. doi: 10.2147/COPD.S132961. eCollection 2017.
PubMed 28546748Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, Frith P, Halpin DM, Lopez Varela MV, Nishimura M, Roche N, Rodriguez-Roisin R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agusti A. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med. 2017 Mar 1;195(5):557-582. doi: 10.1164/rccm.201701-0218PP.
PubMed 28128970Ni Y, Shi G, Yu Y, Hao J, Chen T, Song H. Clinical characteristics of patients with chronic obstructive pulmonary disease with comorbid bronchiectasis: a systemic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2015 Jul 28;10:1465-75. doi: 10.2147/COPD.S83910. eCollection 2015.
PubMed 26251586Figueiredo Bde C, Ibiapina Cda C. The role of macrolides in noncystic fibrosis bronchiectasis. Pulm Med. 2011;2011:751982. doi: 10.1155/2011/751982. Epub 2011 Sep 5.
PubMed 22292118Chalmers JD. Bronchiectasis and COPD Overlap: A Case of Mistaken Identity? Chest. 2017 Jun;151(6):1204-1206. doi: 10.1016/j.chest.2016.12.027. No abstract available.
PubMed 28599926
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Long-Term Macrolide Therapy in Patients With COPD-Bronchiectasis Overlap Syndrome
- ClinicalTrials.gov ID
- NCT04215172
- Acronym / sponsor ID
- COPD_bronchiactasis
- Conditions
- Bronchiectasis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Aug 2020 (estimated)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 1 Jul 2022 (estimated)
- First posted
- 2 Jan 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.
To assess safety of long-term macrolide therapy in patients with COPD-bronchiectasis overlap syndrome And evaluate its efficacy in treating COPD-bronchiectasis overlap syndrome regarding change in clinical, functional and microbiological profile.
To define the, clinical, radiological, functional and microbiological patterns of patients with COPD-bronchiectasis overlap syndrome
Detailed description
COPD and bronchiectasis share common symptoms of cough with sputum production and susceptibility to recurrent exacerbations driven by new or persistent infection The overlap between chronic obstructive pulmonary disease (COPD) and bronchiectasis is a neglected area of research, and it is not covered by guidelines for clinical practice COPD is diagnosed on the basis of poorly reversible airflow obstruction and is therefore a physiological diagnosis. It is defined when an objective measure of airflow obstruction is associated with an abnormal inflammatory response of the lung to noxious stimuli, with cigarette smoke being the most common exposure in the developed world. Operationally, this implies that patients with any sufficient exposure and fixed airflow obstruction are labelled as having COPD.
Bronchiectasis is diagnosed in the presence of airway dilatation and airway wall thickening on imaging (usually computed tomography (CT)), and is therefore a structural diagnosis. Clinically significant disease is present when imaging abnormalities are associated with symptoms of persistent or recurrent bronchial infection.
in the 2014 Global initiative for chronic Obstructive Lung Disease guidelines, bronchiectasis was for the first time defined as a comorbidity of chronic obstructive pulmonary disease (COPD), and this change has been retained in the 2015 update, which emphasizes the influence of bronchiectasis in the natural history of COPD.
The prevalence of bronchiectasis in patients with COPD is high, especially in advanced stages. The identification of bronchiectasis in COPD has been defined as a different clinical COPD phenotype with greater symptomatic severity, more frequent chronic bronchial infection and exacerbations, and poor prognosis.
A recent meta-analysis by Du et al, of 5,329 COPD patients found a greatly increased exacerbation risk due to comorbid COPD with bronchiectasis compared to COPD alone.18 Moreover, the risk of exacerbations rose almost two times higher, colonization of the lungs four times higher, severe airway obstruction 30 percent higher, and mortality two times higher. It is not surprising that such elevated risks are also associated with higher healthcare costs.
Treatments useful in COPD may not be widely effective in bronchiectasis and vice versa. Inhaled corticosteroids provide perhaps the best example of this: they are widely used in COPD but not recommended for most patients with bronchiectasis . The reasons for this are unclear but probably reflect, in part, the diverse aetiology underlying bronchiectasis. In contrast, inhaled antibiotics, including antipseudomonal agents in appropriate patients, are of benefit and appear in current bronchiectasis guidelines ,but are not used routinely in stable COPD Macrolides, in addition to their antimicrobial effects, have decreased neutrophil chemotaxis and infiltration into the respiratory epithelium, inhibition of transcription factors leading to decreased proinflammatory cytokine production, down-regulation of adhesion molecule expression, inhibition of microbial virulence factors including biofilm formation, reduced generation of oxygen-free radicals, enhanced neutrophil apoptosis, and decreased mucus hypersecretion with improved mucociliary clearance.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| macrolides group | – | Drug: MacrolidesEvery patient of this group will be educated and instructed about usage, dosing and side effects of the drug. Dose: azithromycin 500 mg three times weekly for 6 months. added to the conventional treatment. |
| conventional group | – | –Every patient of this group will receive the conventional treatment. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients who are admittted toChest department of Assiut University Hospitals or visit its outpatients' clinic
Key inclusion criteria (4 listed)
- Aged 18 years or above, male or female.
- Non / Ex-smokers.
- Confirmed diagnosis of bronchiectasis based on high-resolution computed tomography scan.
- Confirmed diagnosis of COPD based on pulmonary function test.
Key exclusion criteria (4 listed)
- Active smokers.
- Moderate to severe liver impairment (Child-Pugh B or C) and/or sever renal impairment (c. clearance less than 30ml/min).
- Patients who are known to be hypersensitive to macrolide.
- Patient with known or susceptible to have rhythm problems
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 |
|---|---|---|
| Macrolidesadministration of azithromycin three times weekly for six months | Drug | macrolides group |
Primary outcome
long-term macrolides therapy in patients with COPD-bronchiectasis overlap syndrome regarding ototoxicity, hepatotoxicity and cardiac toxicity
Time frame: two years
1)-ototoxicity by whispered- voice test before starting treatment and monthly The examiner stands arm's length (0.6 m) behind the seated patient and whispers a combination of numbers and letters (for example, 4-K-2) and then asks the patient to repeat the sequence. If the patient responds correctly, hearing is considered normal; if the patient responds incorrectly, the test is repeated using a different number/letter combination The examiner always stands behind the patient to prevent lip reading The other ear is assessed similarly with a different combination of numbers and letters -2)-assessment of hepatotoxicity by measuring liver enzymes (aspartate transaminase AST, Alanine transaminase ALT (Unit/Liter)) before starting treatment and monthly. 3)-assessment of possible prolongation of QT interval (millimeters) by ECG (electrocardiogram) before starting treatment and monthly.
evaluate macrolides in treating COPD-bronchiectasis overlap syndrome regarding improvement of symptoms, frequency of exacerbations, systemic inflammatory response and pulmonary function tests.
Time frame: two years
* symptoms: 1. Dyspnea score by mMRC (modified medical research council) score, with strenuous exercise 0 when hurrying or walking up a slight hill +1 Walks slower than people of the same age because of dyspnea +2 Stops for breath after walking 100 yards +3 Too dyspneic to leave house +4 2. sputum volume by (milliliter), 3. bronchiectasis health questionnaire (BHS) * exacerbation: Frequency of outpatient visits per month and hospital admission if happened (number\month). * systemic inflammation: 1. CBC (complete blood count) (White Blood Cells(n/ microliter), differential count (%) 2. Erythrocyte Sedimentation Rate (millimeter/hour) 3. C-Reactive Protein (milligram\ liter) * Microbiological: Change in microbiological picture based on sputum culture and sensitivity - Functional: Change in FEV1 (forced expiratory volume at one second) (liter/second.) all these will be done before starting treatment and monthly.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2020.
- Background: PubMed 25653262Hurst JR, Elborn JS, De Soyza A; BRONCH-UK Consortium. COPD-bronchiectasis overlap syndrome. Eur Respir J. 2015 Feb;45(2):310-3. doi: 10.1183/09031936.00170014. No abstract available.
- Background: PubMed 20627931Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58. doi: 10.1136/thx.2010.136119.
- Background: PubMed 28546748Martinez-Garcia MA, Miravitlles M. Bronchiectasis in COPD patients: more than a comorbidity? Int J Chron Obstruct Pulmon Dis. 2017 May 11;12:1401-1411. doi: 10.2147/COPD.S132961. eCollection 2017.
- Background: PubMed 28128970Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, Frith P, Halpin DM, Lopez Varela MV, Nishimura M, Roche N, Rodriguez-Roisin R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agusti A. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med. 2017 Mar 1;195(5):557-582. doi: 10.1164/rccm.201701-0218PP.
- Background: PubMed 26251586Ni Y, Shi G, Yu Y, Hao J, Chen T, Song H. Clinical characteristics of patients with chronic obstructive pulmonary disease with comorbid bronchiectasis: a systemic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2015 Jul 28;10:1465-75. doi: 10.2147/COPD.S83910. eCollection 2015.
- Background: PubMed 22292118Figueiredo Bde C, Ibiapina Cda C. The role of macrolides in noncystic fibrosis bronchiectasis. Pulm Med. 2011;2011:751982. doi: 10.1155/2011/751982. Epub 2011 Sep 5.
- Background: PubMed 28599926Chalmers JD. Bronchiectasis and COPD Overlap: A Case of Mistaken Identity? Chest. 2017 Jun;151(6):1204-1206. doi: 10.1016/j.chest.2016.12.027. No abstract available.
- Individual participant dataSharing planned: Undecided
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Bronchiectasis, run by Assiut University.
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 4 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 22 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact alaa s ali, assistant lacturer (01064336300 ext. +2, a_s_a.1990@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
long-term macrolides therapy in patients with COPD-bronchiectasis overlap syndrome regarding ototoxicity, hepatotoxicity and cardiac toxicity (time frame: two years). 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?
On the ClinicalTrials.gov record for NCT04215172, which also lists 7 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 22 Jul 2020.