Assessment of the effects on immunity of azithromycin in pulmonary tuberculosis patients
| ISRCTN | ISRCTN74599367 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN74599367 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | TMA2019CDF-2737 |
| Sponsor | Fondation Congolaise Pour La Recherche Médicale |
| Funder | European and Developing Countries Clinical Trials Partnership |
- Submission date
- 16/10/2024
- Registration date
- 22/10/2024
- Last edited
- 21/10/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Tuberculosis (TB) is a serious infectious disease with high morbidity and mortality rates, especially in developing countries. Even if appropriate and timely initiation of the standard treatment regimen eradicates Mycobacterium tuberculosis, up to half of tuberculosis survivors have some form of persistent lung dysfunction due to an exacerbated inflammatory response. Azithromycin suppresses the production of inflammatory cytokines and as such is a promising adjunct to current tuberculosis treatment to prevent long-term pulmonary complications. The objective of the AZT-TB project is to conduct a pilot clinical study evaluating the immunomodulatory effects of azithromycin in Congolese patients with pulmonary tuberculosis.
Who can participate?
Patients aged 18 to 80 years old who have a clinical diagnosis of drug-sensitive pulmonary tuberculosis
What does the study involve?
This study will examine whether adding azithromycin to standard care has beneficial effects on lung health, as measured by chest X-rays and lung function tests.
What are the possible benefits and risks of participating?
Fair subject selection
Consistent with the scientific purpose, people will be chosen in a way that minimizes risks and enhances benefits to patients and society. Patients who will accept the risks and burdens of research will be in a position to enjoy its benefits, and those who may benefit will share some of the risks and burdens.
Favorable risk-benefit ratio
Everything will be done to minimize the risks and inconvenience to research patients, to maximize the potential benefits, and to determine that the potential benefits to patients and Congolese society are proportionate to, or outweigh, any risk or burden.
Briefly
Benefits: to have full access to clinicians during more than one-year follow-up and to have access to treatment not only for TB but for some diseases like malaria. To participate in a study that will impact the lives of all future TB patients because data will be carefully analysed and will contribute to future decisions by health stakeholders.
Respect for potential and enrolled subjects
Individuals will be treated with respect from the time they are approached for possible participation—even if they refuse enrollment in a study—throughout their participation and after their participation ends.
This includes:
Respecting their privacy and keeping their private information confidential
Respecting their right to change their mind, to decide that the research does not match their interests, and to withdraw without penalty
Informing them of new information that might emerge in the course of research, that might change their assessment of the risks and benefits of participating
Monitoring their welfare and, if they experience adverse reactions, untoward events, or changes in clinical status
Ensuring appropriate treatment and, when necessary, removal from the study
Informing them about what was learned from the research
Risks:
To have external people know about your personal life conditions but the confidentiality will be strictly kept therefore this risk is minimized. Individuals will give informed consent in which individuals (1) are accurately informed of the purpose, methods, risks, benefits, and alternatives to the research, (2) understand this information and how it relates to their clinical situation or interests, and (3) make a voluntary decision about whether to participate.
Where is the study run from?
Congolese Foundation for Medical Research (Fondation Congolaise Pour La Recherche Médicale)
When is the study starting and how long is it expected to run for?
October 2020 to December 2024
Who is funding the study?
European and Developing Countries Clinical Trials Partnership
Who is the main contact?
Prof Francine Ntoumi, fntoumi@fcrm-congo.com, ffntoumi@hotmail.com
Contact information
Public, Scientific, Principal investigator
FCRM - Fondation Congolaise pour la recherche médicale, villa D6, campus OMS AFRO, Djoue
Brazzaville
COG
Congo
 ORCID ID |
0000-0003-4748-050X |
|---|---|
| Phone | +242069977980 |
| fntoumi@fcrm-congo.com |
Public
FCRM - Fondation Congolaise pour la recherche médicale, villa D6, campus OMS AFRO, Djoue
Brazzaville
COG
Congo
| Phone | +242069977980 |
|---|---|
| ffntoumi@hotmail.com |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Interventional prospective randomized two-arm open-label pilot study |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Assessment of immunomodulatory effects of azithromycin in pulmonary tuberculosis patients |
| Study acronym | AZT-TB |
| Study objectives | Azithromycin in combination with standard care may prevent the formation of persistent lung lesions via its immunomodulatory effects |
| Ethics approval(s) |
Approved 08/10/2020, Institutional Ethics Committee of The Congolese Foundation for Medical Research (CERMI, cite de la recherche ex-ORSTOM, quartier Château-d'eau, Brazzaville, XXXX, Congo; +242 06 672 31 22; kcaryel@yahoo.fr), ref: 029/CIE/FCRM/2020 |
| Health condition(s) or problem(s) studied | Pulmonary tuberculosis |
| Intervention | This study is a prospective randomized study that will be carried out to evaluate the immunomodulatory effect of azithromycin in tuberculosis patients. A sputum smear microscopy, Xpert MTB/RIF, a mycobacterial culture and a chest x-ray will be performed to diagnose pulmonary tuberculosis in patients with suspicious symptoms of tuberculosis (including cough > two weeks, weight loss, fatigue, fever, sweats nocturnal). Online probe testing (LPA) will be performed using the Genotype MTBDR test (no longer commercially available), to exclude patients with drug-resistant tuberculosis from the study. The HIV test will be carried out according to the guidelines of tuberculosis management and HIV-positive patients will be excluded from the study. The patients will be enrolled after consent and ethical approval. A manual method of randomization (flip a coin and get heads = with or tails = without) will be used to allocate patients to the standard of care (2HRZE/4HR) with or without azithromycin treatment. The study will be conducted as an open-label study. Azithromycin will be administered at an initial dose of 500 mg followed by 250 mg once a day daily for 28 days in the form of a film-coated tablet. Patients in both arms of treatment will be stratified according to disease severity, age and gender. The patients will be recruited over 12 months and followed for 12 months. The study will enrol 50 adults (>18 years) of both sexes with a first episode of tuberculosis pulmonary, seronegative, sensitive to all first-line drugs and living at Brazzaville. Patients in both treatment arms will be matched as much as possible for disease severity, age and sex. Pulmonary manifestations will be evaluated at each follow-up consultation using a chest x-ray and pulmonary function test. |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 2HRZE/4HR, Azithromycin |
| Primary outcome measure(s) |
The following primary outcome measures will be assessed before randomization, week 2, months 1, 2, 6 and 12: |
| Key secondary outcome measure(s) |
The following secondary outcome measures will be assessed before randomization, week 2, months 1, 2, 6 and 12: |
| Completion date | 31/12/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 80 Years |
| Sex | All |
| Target sample size at registration | 50 |
| Total final enrolment | 50 |
| Key inclusion criteria | 1. Clinical diagnosis of drug-sensitive pulmonary tuberculosis (molecular test identification of the Mtb complex; absence of resistance genes such as rpob, inha, katg) 2. Written informed consent |
| Key exclusion criteria | 1. The patient has reported a history of treatment for tuberculosis 2. Patients under 18 years old 3. Pregnancy or breastfeeding 4. Patients with hypersensitivity to macrolide antibiotics 5. Treatment with a macrolide during the previous month 6. Treatment with tetracycline during the previous month 7. Treatment with any inhaled or oral corticosteroid within the previous month 8. Concomitant treatment with analgesics (NSAIDs)/immunosuppressants (except paracetamol) 9. Digoxin treatment 10. Patients with gastrointestinal disorders, such as diarrhea and vomiting (≥ grade 2, observed) 11. Patients with a history of cholestatic jaundice/liver dysfunction associated with previous use of Azithromycin 12. Other known respiratory diseases, including bronchiectasis, pulmonary fibrosis, disease pulmonary vascular or lung cancer 13. HIV infection or AIDS |
| Date of first enrolment | 31/10/2020 |
| Date of final enrolment | 31/10/2023 |
Locations
Countries of recruitment
- Congo
Study participating centre
Brazzaville
COG
Congo
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Stored in publicly available repository |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a publically available repository (currently unknown). Clinical and socio-demographic data will be shared as soon as the trial is completed and the results published. To request access please contact the Principal investigator, Prof Francine Ntoumi, fntoumi@fcrm-congo.com, ffntoumi@hotmail.com, after first publication in 2027. Consent from participants was required and obtained. Data anonymization was undertaken via a code given at enrolment and only PI and co-Pi may link the code to an individual name. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | 21/10/2024 | No | No |
Additional files
- 46233_Protocol.pdf
- Protocol file
Editorial Notes
21/10/2024: Study's existence confirmed by the Institutional Ethics Committee of The Congolese Foundation for Medical Research.
