Azithromycin as Host-directed Therapy for Pulmonary Tuberculosis

NCT ID: NCT03160638

Last Updated: 2024-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-01
• Study Completion Date: 2022-05-22

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.

Conditions

Tuberculosis, Pulmonary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Azithromycin arm

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

Group Type: EXPERIMENTAL

Azithromycin 250 mg

Intervention Type: DRUG

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

Standard of care arm

Patients in this arm will receive no additional treatment on top of standard HRZE treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Jan-Willem C Alffenaar

Principal Investigator, PharmD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Medical Center Groningen

Groningen, , Netherlands

Countries

Netherlands

References

Dekkers BGJ, Kerstjens HAM, Breisnes HW, Leeming DJ, Anthony RM, Frijlink HW, van der Werf TS, Kosterink JGW, Alffenaar JC, Akkerman OW. Azithromycin as Host-Directed Therapy for Pulmonary Tuberculosis: A Randomized Pilot Trial. J Infect Dis. 2025 Jun 2;231(5):e891-e900. doi: 10.1093/infdis/jiaf069.

Reference Type: DERIVED

PMID: 39932906 (View on PubMed)

Other Identifiers

AZT_DSTB_BB

Identifier Type: -

Identifier Source: org_study_id