Macrolides in COPD- Bronchiectasis Overlap

July 20, 2020 updated by: Alaa Sayed Ali, Assiut University

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

patients who are admittted toChest department of Assiut University Hospitals or visit its outpatients' clinic

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Drug: Macrolides
administration of azithromycin three times weekly for six months
conventional group
Every patient of this group will receive the conventional treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
two years
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.
two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

August 1, 2020

Primary Completion (Anticipated)

January 1, 2022

Study Completion (Anticipated)

July 1, 2022

Study Registration Dates

First Submitted

December 18, 2019

First Submitted That Met QC Criteria

December 29, 2019

First Posted (Actual)

January 2, 2020

Study Record Updates

Last Update Posted (Actual)

July 22, 2020

Last Update Submitted That Met QC Criteria

July 20, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COPD_bronchiactasis

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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