Azithromycin as Host-directed Therapy for Pulmonary Tuberculosis

Phase 2

Completed

• Conditions: Tuberculosis, Pulmonary
• Interventions: Drug: Azithromycin 250 mg

• Registration Number: NCT03160638
• Lead Sponsor: University Medical Center Groningen

Brief Summary

Rationale:

Treatment in tuberculosis (TB) is focused on eradication of the bacterial infection, however, after treatment approximately half of patients are left with a significant and permanent respiratory impairment. Adjunctive host-directed therapies are being investigated to modulate host immune responses to target mycobacterium tuberculosis (Mtb) infection and/or reduce excessive inflammation, prevent pathological tissue damage, preserve lung function and enhance effectiveness of standard drug therapy, while nonetheless eliminating Mtb. Macrolide antibiotics have previously been used in the treatment of multidrug-resistant TB. In addition to their antibiotic effects, macrolides have also been recognized to induce anti-inflammatory and immunomodulatory effects in other lung diseases.

Objective:

To investigate the immunomodulatory effects of azithromycin in tuberculosis patients receiving standard therapy (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE))

Study design:

A prospective, randomized open label intervention trial to investigate the immunomodulatory effects of azithromycin

Study population: 24

Intervention: azithromycin 250 mg once daily or standard of care (control)

Main study parameters/endpoints:

1. To assess whether azithromycin enhances resolution of systemic inflammation in patients with drug susceptible pulmonary TB receiving standard treatment.

2. To assess whether azithromycin on top of standard treatment in patients with drug susceptible pulmonary TB reduces airway inflammation and reduces tissue degradation and remodeling

3. To investigate whether these effects are associated within shortening of the time to sputum conversion.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-05-11
• Study First Submitted QC: 2017-05-18
• Study First Posted: 2017-05-19
• Study Start: 2018-02-01
• Primary Completion: 2022-05-22
• Study Completion: 2022-05-22
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-23
• Last Update Posted: 2024-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Clinical diagnosis of drug sensitive pulmonary tuberculosis (molecular test; identification Mtb complex; absence of resistance genes such as rpob, inha, katg)
• Written informed consent

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Exclusion Criteria

• Patient reported previous history of treatment for tuberculosis
• Patients younger than 18 years
• Pregnancy or breast feeding
• Patients with hypersensitivity to macrolide antibiotics
• Treatment with any macrolide in the previous month
• Treatment with any tetracycline in the previous month
• Treatment with any inhaled or oral corticosteroid in the previous month
• Concomitant treatment with analgesic (NSAIDs)/immunosuppressant drugs (except paracetamol).
• Treatment with digoxin
• Patients with gastrointestinal complaints, like diarrhea and vomiting (≥grade 2, observed)
• Other known respiratory diseases, including bronchiectasis, pulmonary fibrosis, pulmonary vascular disease or lung cancer
• HIV-1 infection or AIDS
• Impaired liver function (Child-Pugh score C)
• Patients with a known QTc ≥500 ms. An electrocardiogram (ECG) will be recorded.
• Inability to spontaneously produce sputum upon diagnosis

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Azithromycin arm	Azithromycin 250 mg	Patients in this arm will be treated with azithromycin 250 mg once daily on top of standard HRZE treatment.

Primary Outcome Measures

Name	Time	Method
Systemic inflammation	Before randomization, day 7 and day 28	Changes in serum inflammatory markers

Secondary Outcome Measures

Name	Time	Method
Pulmonary inflammation	Before randomization and day 28	Changes in cytokine levels in sputum
Pulmonary tissue degradation	Before randomization, day 7 and day 28	Changes in markers of tissue degradation in serum
Pulmonary tissue remodeling	Before randomization, day 7 and day 28	Changes in markers of tissue remodeling in serum

Trial Locations

Locations (1)

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands