A study on the anti-inflammatory effects of azithromycin in tuberculosis

Phase 1

• Conditions: Pulmonary tuberculosis; MedDRA version: 20.0Level: PTClassification code 10037440Term: Pulmonary tuberculosisSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2017-001929-40-NL
• Lead Sponsor: niversity Medical Center Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-08-24
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study (most of these criteria are recorded as standard of care):
-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). See attachment A for a full list of these drugs.
-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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess whether azithromycin enhances resolution of systemic inflammation in patients with drug susceptible pulmonary TB receiving HRZE treatment. ;Secondary Objective: To assess whether azithromycin on top of HRZE treatment in patients with drug susceptible pulmonary TB:<br>1.Reduces airway inflammation <br>2.Reduces pulmonary tissue degradation and airway remodeling <br>;Primary end point(s): Systemic inflammation as assessed by:<br>-Changes in total white blood cell count and blood cell differential counts<br>-Changes in serum inflammatory markers (C-reactive protein (CRP), serum amyloid A (SAA), procalcitonin, interferon-? (IFN-?), Interleukin-2 (IL-2), IL-4, IL-6, IL-8, IL-10, IL-17, Myeloperoxidase (MPO), Neutrophil elastase (NE), Tumor necrosis factor-a (TNF-a)).<br>;Timepoint(s) of evaluation of this end point: At randomization, day 7 and day 28

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Pulmonary inflammation as assessed by:<br>-Changes in inflammatory cell counts and differential cell counts in sputum<br>-Changes in cytokine levels in sputum (IFN-?, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, MPO, NE, TNF-a). <br>Pulmonary tissue degradation and remodeling as assessed by:<br>-Markers of tissue degradation in sputum and serum (C1M (MMP generated fragment of collagen type I). C3M (MMP generated fragment of collagen type III), C6M (MMP generated fragment of collagen type VI), EL-NE (an elastin fragment generated by neutrophil elastase), MMP-8 (matrix metalloprotease-8), MMP-9).<br>-Markers of remodeling in sputum and serum (Pro-C3 (a formation marker of collagen III), Pro-C6 (a formation marker of collagen VI), transforming growth factor-ß (TGF-ß))<br>;Timepoint(s) of evaluation of this end point: At randomization, day 7 and day 28