Azithromycin as Host-directed Therapy for Pulmonary Tuberculosis

University Medical Center Groningen (UMCG)

Status and phase: Completed; Phase 2

Conditions: Tuberculosis, Pulmonary

Treatments: Drug: Azithromycin 250 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT03160638

AZT_DSTB_BB

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Azithromycin arm

Experimental group

Description:

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

Treatment:

Drug: Azithromycin 250 mg

Standard of care arm

No Intervention group

Description:

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