Azithromycin Treatment for the Airway Microbiome in Asthma

The AZITRAMBA Trial: Azithromycin Treatment for the Airway Microbiome in Asthma

The purpose of this study to determine whether the bacteria inside the lungs of people with asthma can be modified (changed) if they are given an antibiotic and if this change is associated with an improvement in asthma symptoms.

Study Overview

• Status: Terminated
• Conditions: Asthma Chronic
• Intervention / Treatment: Drug: Placebo; Drug: Azithromycin

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60201
      • Northwestern University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria (All participants):

1. Age 18 - 55 years
2. Able to provide informed consent
3. Smoking history < 10 pack-years

Inclusion Criteria for subjects with poorly controlled asthma

1. Methacholine PC20 < 16 mg/ml or PD 20 < 400 mcg/ml or albuterol response > 12% on FEV1 after 4 puffs of albuterol
2. Currently prescribed ICS + LABA
3. Meet definition for Th2-low asthma: peripheral blood eosinophil count < 300 and exhaled nitric oxide level < 30 ppb.

Exclusion Criteria (All participants)

1. History of allergy or intolerance to any medications used in this study

2. Medication exclusions:

   1. Current use of medications that prolong QTc interval
   2. Current use of omalizumab or other ant-IgE therapies
   3. Current use of anti-IL 5 therapies
   4. Current use of anticoagulants
3. Prednsione or other oral steroids within past 3 months
4. Pregnancy or lactation, or plans to become pregnant
5. Other respiratory or inflammatory disorders (e.g., sarcoidosis, emphysema)
6. Pre-existing liver disease by history
7. Smoking within the last 6 months
8. Exacerbation of asthma in past 3 months
9. Affected by a hearing disorder
10. Clinically significant medical condition (e.g., heart failure, seizure disorder) which may in-crease risk as determined by study investigator
11. Corrected QT interval > 450 msec. Patients with known cardiac history or prolonged QT interval on a screening EKG are excluded given the small but real potential for macrolide-related side effects

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 8 weeks of placebo capsule once daily by mouth	Drug: Placebo; Placebo
Active Comparator: Azithromycin; 8 weeks of Azithromycin (250 mg) capsule once daily by mouth	Drug: Azithromycin; 8 weeks of Azithromycin (250 mg) once daily by mouth; Other Names: Zithromax
No Intervention: Non-asthmatic controls; Non-asthmatic controls to assess variability of microbiome composition and diversity over time in a normal population. No intervention given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asthma Control Test (ACT) Score Change From Baseline Over 8 Weeks	Score ranging from 0 to 40 indicating the degree of asthma symptoms. Lower score indicating worse asthma symptoms.	Baseline and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume (FEV1) Change From Baseline Over 8 Weeks	Volume of air exhaled in 1 second on a forced expiration, expressed as percent of predicted, indicating the degree of airflow obstruction in asthma	8 weeks
Sputum Eosinophils Change From Baseline Over 8 Weeks	Percentage of 'eosinophils', an inflammatory cell seen in the airways of people with asthma, indicating the degree of inflammation	Baseline and 8 weeks
Sputum Neutrophils Change From Baseline Over 8 Weeks	Percentage of 'neutrophils', an inflammatory cell seen in the airways of people with asthma, indicating the degree of inflammation	Baseline and 8 weeks
Number of Participants With Diary Event or Serious Asthma Exacerbation Over 8 Weeks	The outcome is derived from a weighted scoring system called CompEx that describes asthma symptoms recorded on a daily basis. Final result is a dichotomous outcome indicating whether the patient had a "diary event" based on changes in peak expiratory flow, reliever use, and asthma symptoms or a serious exacerbation (deterioration of asthma leading to oral corticosteroid use, emergency room admission, or hospital admission).	8 weeks
Microbiome Shannon Alpha-diversity Score Change From Baseline to 8 Weeks	A measure of the diversity of the bacteria in the sputum or oral sample; that is, how many different types of bacteria are present. This value decreases in severe asthma	8 weeks
Microbiome Beta-diversity Score Change From Baseline to 8 Weeks	A second measure of the diversity of the bacteria in the sputum or oral sample; that is, how many different types of bacteria are present. This value decreases in severe asthma	8 weeks
Microbiome Change in Relative Proportion of Top 10 Genera From Baseline to 8 Weeks	A measure of how many of the top types of bacteria are present in the sputum or oral sample. Value changes with asthma	8 weeks

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: Northwestern University
• Investigators: Principal Investigator: Steve White, MD, University of Chicago

Publications and helpful links

General Publications

• Vogelmeier CF, Fuhlbrigge A, Jauhiainen A, Scheepers LEJM, Bengtsson T, Peterson S, Karlsson N, Sethi T, Locantore N, Tal-Singer R, Rennard S, Fageras M, Da Silva CA. COPDCompEx: A novel composite endpoint for COPD exacerbations to enable faster clinical development. Respir Med. 2020 Nov;173:106175. doi: 10.1016/j.rmed.2020.106175. Epub 2020 Sep 28.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: November 7, 2018
• First Submitted That Met QC Criteria: November 8, 2018
• First Posted (Actual): November 9, 2018

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Microbiome; Asthma; Azithromycin; Sputum
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: IRB17-1287

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share individual participant data that is de-identified available to all qualified investigators
• IPD Sharing Time Frame: Upon publication of the major manuscript to be generated from this study. Data will be deposited in an appropriate major database (e.g., sequencing information will be deposited in a genetics bio-bank).
• IPD Sharing Access Criteria: All qualified investigators who sign appropriate data use agreements and material transfer agreements with the University of Chicago and Northwestern University
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

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.: Yes