Tuberculosis, PulmonaryPhase 2NCT03160638
Azithromycin as Host-directed Therapy for Pulmonary Tuberculosis
A Phase 2 study testing Azithromycin 250 mg in people with Tuberculosis, Pulmonary, run by University Medical Center Groningen at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Tuberculosis, Pulmonary
- What is being tested?
- Azithromycin 250 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Feb 2018to 22 May 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of drug sensitive pulmonary tuberculosis (molecular test; identification Mtb complex; absence of resistance genes such as rpob, inha, katg)
- Written informed consent
Who cannot join
- 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
Show all 15Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Randomized Pilot Study of the Immunomodulatory Effects of Azithromycin in Adults With Pulmonary Tuberculosis
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.
Read more
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:
- To assess whether azithromycin enhances resolution of systemic inflammation in patients with drug susceptible pulmonary TB receiving standard treatment.
- 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
- To investigate whether these effects are associated within shortening of the time to sputum conversion.
- Conditions
- Tuberculosis, Pulmonary
- Being tested
- Azithromycin 250 mg
- Keywords
- Azithromycin, Immunomodulation, Pharmacokinetics, Tissue degradation, Tissue remodelling
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azithromycin 250 mgDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin arm | Experimental | Patients in this arm will be treated with azithromycin 250 mg once daily on top of standard HRZE treatment. Receives: Drug: Azithromycin 250 mg |
| Standard of care arm | No intervention | Patients in this arm will receive no additional treatment on top of standard HRZE treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Systemic inflammation
Changes in total \& differential white blood cell counts markers
Measured: Before randomization, day 7 and day 28
Systemic inflammation
Changes in serum inflammatory markers
Measured: Before randomization, day 7 and day 28
Secondary outcomes (6)
Pulmonary inflammation
Changes in total and differential sputum inflammatory cell counts
Measured: Before randomization and day 28
Pulmonary inflammation
Changes in cytokine levels in sputum
Measured: Before randomization and day 28
Pulmonary tissue degradation
Changes in markers of tissue degradation in sputum
Measured: Before randomization and day 28
Pulmonary tissue degradation
Changes in markers of tissue degradation in serum
Measured: Before randomization, day 7 and day 28
Pulmonary tissue remodeling
Changes in markers of tissue remodeling in sputum
Measured: Before randomization and day 28
Pulmonary tissue remodeling
Changes in markers of tissue remodeling in serum
Measured: Before randomization, day 7 and day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2017
- Study start1 Feb 2018
- Primary completion22 May 2022
- Study completion22 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tuberculosis, PulmonaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, randomized pilot study
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jan-Willem C Alffenaar, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03160638
- Sponsor's protocol ID
- AZT_DSTB_BB
- Status last verified
- Feb 2024
- First submitted
- 11 May 2017
- Last updated
- 26 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39932906
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized Pilot Study of the Immunomodulatory Effects of Azithromycin in Adults With Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT03160638
- Acronym / sponsor ID
- AZT_DSTB_BB
- Conditions
- Tuberculosis, Pulmonary
- Keywords
- Azithromycin, Immunomodulation, Pharmacokinetics, Tissue degradation, Tissue remodelling
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 22 May 2022 (actual)
- Study completion
- 22 May 2022 (actual)
- First posted
- 19 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To assess whether azithromycin enhances resolution of systemic inflammation in patients with drug susceptible pulmonary TB receiving standard treatment.
- 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
- To investigate whether these effects are associated within shortening of the time to sputum conversion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, randomized pilot study
| Arm | Type | Receives |
|---|---|---|
| Azithromycin arm | Experimental | Drug: Azithromycin 250 mgPatients in this arm will be treated with azithromycin 250 mg once daily on top of standard HRZE treatment. |
| Standard of care arm | No intervention | –Patients in this arm will receive no additional treatment on top of standard HRZE treatment |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Clinical diagnosis of drug sensitive pulmonary tuberculosis (molecular test; identification Mtb complex; absence of resistance genes such as rpob, inha, katg)
- Written informed consent
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azithromycin 250 mgPatients 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 | Drug | Azithromycin arm |
Primary outcome
Systemic inflammation
Time frame: Before randomization, day 7 and day 28
Changes in total \& differential white blood cell counts markers
Systemic inflammation
Time frame: Before randomization, day 7 and day 28
Changes in serum inflammatory markers
6 secondary outcomes
Pulmonary inflammation
Time frame: Before randomization and day 28
Pulmonary inflammation
Time frame: Before randomization and day 28
Pulmonary tissue degradation
Time frame: Before randomization and day 28
Pulmonary tissue degradation
Time frame: Before randomization, day 7 and day 28
Pulmonary tissue remodeling
Time frame: Before randomization and day 28
Pulmonary tissue remodeling
Time frame: Before randomization, day 7 and day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2024.
- Derived from this study: PubMed 39932906Dekkers 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azithromycin 250 mg in people with Tuberculosis, Pulmonary, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Systemic inflammation (time frame: Before randomization, day 7 and day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03160638, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2024.