Clinical trial NCT03251196: TB Sequel: Pathogenesis and Risk Factors of Long-term Sequelae of Pulmonary TB
Official title: TB Sequel: Pathogenesis and Risk Factors of Long-term Sequelae of Pulmonary TB Defining Individual Outcomes and Public Health Impact
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Respiratory Tract Infections
Tuberculosis, Pulmonary
Lead sponsor: The Aurum Institute NPC
Sponsor class: OTHER
Collaborators: name: Ludwig-Maximilians - University of Munich
name: Research Center Borstel
name: University of Witwatersrand, South Africa
name: Mbeya Medical Research Centre NIMR
name: Ministry of Health Instituto Nacional de Saude
name: Medical Research Council Unit, The Gambia
name: Karolinska Institutet
First posted: 2017-08-16
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This will be a multi-country, multi-centre observational cohort study, conducted at four recruiting sites in four African countries: 1) University of the Witwatersrand (WITS), Johannesburg in South Africa; 2) NIMR-Mbeya Medical Research Center (NIMR-MMRC), Mbeya in Tanzania; 3) Instituto Nacional de Saúde (INS), Ministry of Health, Mozambique; 4) Medical Research Council (MRC) Unit The Gambia, Fajara, The Gambia.

Brief summary: This is an observational cohort study. Pulmonary tuberculosis (TB) patients will be enrolled at the time of TB diagnosis and prospectively followed for at least two years after TB-treatment initiation with optional prolonged follow-up. Study visits will be performed in the study clinics or if necessary at the participant's home at pre-defined time points after TB treatment initiation. Clinical assessments, biological sample collections and collection of socio-economic data will be performed according to the pre-defined schedule of events.

Detailed description: The African continent today is emblematic of TB as a global health emergency with little known about the long-term sequelae. It is likely that TB patients from resource-constrained settings, who usually present with more extensive disease, are left with greater lung impairment.

This project aims to advance the understanding of the clinical, microbiologic, and host immune factors affecting the long-term sequelae of pulmonary tuberculosis; to identify the most important factors that contribute to lung impairment, including the immunological response and genetic predisposition of the host and differences in the biology of the pathogen; to determine occurrence of reversible and irreversible costs and socioeconomic consequences for patients; and to facilitate novel interventions to restore and preserve overall health, well-being and financial protection in patients with TB.

The core of the current project is a prospective cohort of up to 1600 patients across four countries (Mozambique, Tanzania, South Africa and The Gambia), enrolled at the time of TB diagnosis, and followed up for at least 2 years. The overall goal of the cohort is to describe and analyse the basis of the long-term clinical consequences of pulmonary TB, with a particular focus on lung injury. The investigators will enroll patients during two years and follow each patient up for at least two years. The project also includes a number of sub-studies: Host-Immunology, Pathogen and Socio-Economic. General laboratory tests and TB specific tests, X-ray, physical examination and cardio-pulmonary assessment will be performed and the obtained clinical data will be recorded in study questionnaires. The investigators will collect and analyse biological specimens (blood, urine and sputum) longitudinally during the period of observation and after all specimens have been stored. In-depth analysis of the host immune response, focusing on potential mechanisms of lung damage, including oxidative injury, proteolytic matrix degradation, and neutrophil-mediated damage, neutrophil-macrophage ratios and markers; and molecular analysis of mycobacterial dynamics and markers in relation to pulmonary and microbiological treatment outcomes, including success, failure, relapse, reinfection and death will be carried out. Socio-economic data, including patient costs, will be collected at the time of TB diagnosis, during treatment, at the end of treatment and during the follow-up period, and analysed to determine how the risk of TB sequelae is linked with the socioeconomic position of the patient, to establish the occurrence of catastrophic costs due to TB and the proportion of patients that resort to potentially irreversible socioeconomic coping strategies.

Accurate data source will be maintained and confidentiality will be guaranteed. Data will be analysed according to the statistical plan. Results of the study will be disseminated to all relevant stakeholders through meetings, reports and publications.

Eligibility criteria: Inclusion Criteria:

* At least one sputum sample tested positive for Mtb by Xpert MTB/RIF assay in the study clinic/study laboratory or at least one sputum sample tested positive by culture methods in study laboratory or other TB laboratory
* Be ≥ 18 years of age
* Willingness to provide a written consent or witnessed oral consent in the case of illiteracy for participation in the study, prior to patient's first sample or other study-specific data being collected
* Willing to be tested for HIV infection
* Agrees to the collection and storage of blood, urine, and sputum specimens for use in future research
* Willing to start anti-TB treatment after TB diagnosis
* Living within the study area and willing to inform the study team of any change of address during the treatment and follow-up period

Exclusion Criteria:

* Has received TB treatment in the last 6 months
* Has incapacity to produce and provide two sputum samples of sufficient quality (3 ml)
* Has severe medical or psychiatric condition which in the opinion of the site investigator or designee, might interfere with the ability to give true informed consent and to adhere to the study requirements
* Is currently imprisoned
* Taking part in investigational product trials related to TB and/or lung diseases

Primary outcomes:
measure: Severe pulmonary function impairment
timeFrame: 2 years
Secondary outcomes:
measure: Changes in impairment of pulmonary function
timeFrame: 2 years
Other outcomes:
Locations:
city: Fajara
country: Gambia
facility: The MRC-Unit
city: Maputo
country: Mozambique
facility: Instituto Nacional de Saúde
city: Johannesburg
country: South Africa
facility: The Clinical HIV Research Unit
state: Gauteng
city: Mbeya
country: Tanzania
facility: NIMR-Mbeya Medical Research Centre
Study officials:
affiliation: Chief Executive Officers
name: Gavin J Churchyard
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rachow A, Ivanova O, Wallis R, Charalambous S, Jani I, Bhatt N, Kampmann B, Sutherland J, Ntinginya NE, Evans D, Lonnroth K, Niemann S, Schaible UE, Geldmacher C, Sanne I, Hoelscher M, Churchyard G. TB sequel: incidence, pathogenesis and risk factors of long-term medical and social sequelae of pulmonary TB - a study protocol. BMC Pulm Med. 2019 Jan 7;19(1):4. doi: 10.1186/s12890-018-0777-3.