Azithromycin as Host-directed Therapy for Pulmonary Tuberculosis

Tuberculosis, Pulmonary Clinical Trial

Official title:

A Prospective, Randomized Pilot Study of the Immunomodulatory Effects of Azithromycin in Adults With Pulmonary Tuberculosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03160638
• Other study ID #: AZT_DSTB_BB
• Status: Completed
• Phase: Phase 2
• Start date: February 1, 2018
• Est. completion date: May 22, 2022

Study information

• Verified date: February 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: May 22, 2022
• Est. primary completion date: May 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Drug:
• Azithromycin 250 mg
Patients will be treated with azithromycin 250 mg once daily for 28 days. An azithromycin loading dose of 500 mg (two tablets of 250 mg) will be administered on day 1

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluation of HRZE treatment outcomes	Time to sputum conversion	Up to 6 months
Other	Evaluation of HRZE treatment outcomes	Drug exposure of HRZE in relation to minimal inhibitory concentration (MIC) of Mtb for HRZE	Up to 6 months
Other	Drug exposure of azithromycin	AUC0-24h of azithromycin in TB	Day 7
Other	Drug exposure of azithromycin	Metabolic clearance (CLm) of azithromycin in TB	Day 7
Other	Drug exposure of azithromycin	Volume of distribution (V) of azithromycin in TB	Day 7
Other	Drug exposure of azithromycin	Elimination half-life (T1/2) of azithromycin in TB	Day 7
Primary	Systemic inflammation	Changes in total & differential white blood cell counts markers	Before randomization, day 7 and day 28
Primary	Systemic inflammation	Changes in serum inflammatory markers	Before randomization, day 7 and day 28
Secondary	Pulmonary inflammation	Changes in total and differential sputum inflammatory cell counts	Before randomization and day 28
Secondary	Pulmonary inflammation	Changes in cytokine levels in sputum	Before randomization and day 28
Secondary	Pulmonary tissue degradation	Changes in markers of tissue degradation in sputum	Before randomization and day 28
Secondary	Pulmonary tissue degradation	Changes in markers of tissue degradation in serum	Before randomization, day 7 and day 28
Secondary	Pulmonary tissue remodeling	Changes in markers of tissue remodeling in sputum	Before randomization and day 28
Secondary	Pulmonary tissue remodeling	Changes in markers of tissue remodeling in serum	Before randomization, day 7 and day 28