E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037440 |
E.1.2 | Term | Pulmonary tuberculosis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess whether azithromycin enhances resolution of systemic inflammation in patients with drug susceptible pulmonary TB receiving HRZE treatment. |
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E.2.2 | Secondary objectives of the trial |
To assess whether azithromycin on top of HRZE treatment in patients with drug susceptible pulmonary TB:
1. Reduces airway inflammation
2. Reduces pulmonary tissue degradation and airway remodeling
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Systemic inflammation as assessed by:
- Changes in total white blood cell count and blood cell differential counts
- Changes in serum inflammatory markers (C-reactive protein (CRP), serum amyloid A (SAA), procalcitonin, interferon-γ (IFN-γ), Interleukin-2 (IL-2), IL-4, IL-6, IL-8, IL-10, IL-17, Myeloperoxidase (MPO), Neutrophil elastase (NE), Tumor necrosis factor-α (TNF-α)).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At randomization, day 7 and day 28 |
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E.5.2 | Secondary end point(s) |
Pulmonary inflammation as assessed by:
- Changes in inflammatory cell counts and differential cell counts in sputum
- Changes in cytokine levels in sputum (IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, MPO, NE, TNF-α).
Pulmonary tissue degradation and remodeling as assessed by:
- 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).
- 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-β (TGF-β))
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At randomization, day 7 and day 28 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard of care (no additional treatment). |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |