Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04825327 |
| Other study ID # |
RIA2018D-2509 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 21, 2021 |
| Est. completion date |
September 30, 2025 |
Study information
| Verified date |
March 2024 |
| Source |
Amsterdam Institute for Global Health and Development |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The investigators will study, prospectively, if contacts (household or close contacts) of
tuberculosis (TB) patients with high C-reactive protein (CRP), low hemoglobin (Hb) levels,
and a positive Xpert Host Response (HR) cartridge result develop active TB within 12 months.
They will also investigate if there is a correlation between progressing to active TB within
12 months and having high levels of the iron homeostasis markers (Hepcidin, Ferritin and
Transferrin).
Identified index cases who agree to participate will refer their household or close contacts
to also join the study. These contacts will be tested for TB and only contacts who are
negative will be enrolled and followed-up at 6 months and 12 months. Blood samples will be
collected at baseline and 6 months for testing. During the study period, TB testing will be
done on contacts who meet symptoms criteria. At 12 months, all contacts will undergo a chest
x-ray to assist in the diagnosis of TB.
PreFIT will target people aged 12 to 60 years of age and both HIV negative and positive. 1515
trial participants will be recruited at Stellenbosch University in South Africa, 1515 at
Fundaçao Manhiça in Mozambique and 1010 at Makerere University in Uganda, respectively.
Description:
Although the estimated numbers of people infected with TB in Africa are declining since the
rollout of antiretroviral therapy a decade ago, TB is still the highest in the world. Early
diagnosis and treatment of TB disease are essential to reducing morbidity and mortality.
Transformative progress will never be possible with the current diagnostic tools as they rely
on the detection of active TB which usually happen after disease has already been spread to
others. Diagnostic technologies to accurately detect who will develop active TB are under
development. However, their performance is not well reported.
A better TB prediction test is needed to detect TB before clinical manifestation. The PreFIT
investigators hypothesize that volunteers with a combination of positive Xpert HR result,
high CRP, and/or low Hb levels will likely progress to active TB within 12 months. They also
hypothesize that those with TB will have early high Hepcidin, Ferritin and Transferrin
levels.
The investigators plan to ask those found with TB at the local clinic if they accept to join
the study. The participants, if they consent will then give information about people
(contacts) who they stay with or meet frequently to also join the study. Contacts who have TB
symptoms will be asked to cough sputum to be tested for co-prevalent TB disease. If they are
found not to have TB disease, they will be asked to give blood: few drops from a finger prick
and about 50mls from the vein on the arm to be stored and used for further tests. Follow-up
and sampling of enrolled contacts without co-prevalent active TB will occur at six and 12
months (± 21 days before or after each time point, a six-week total window). Participants
meeting presumptive TB or sputum expectorator definitions at six (M6) or 12 months (M12) of
follow-up, or report with symptoms at any timepoint in-between, will undergo Xpert Ultra (or
Xpert MTB/RIF if Ultra unavailable) and culture testing. All positive cultures will undergo
whole genome sequencing (WGS) to track index case and co-prevalent or incident case
transmission. Chest X-ray (CXR) will be done at M12 to potentially rule-out active disease
missed by microbiological methods. Passive TB diagnoses (microbiological or empirical)
throughout the follow-up period will be captured.
To prevent diagnostic information bias, M0 and M6 test results for Xpert HR, CRP and
haemoglobin will be kept concealed to the study nurse(s) and physician(s) who screen the
cohort participants for active TB during follow-up. Similarly, laboratory technicians who
test the stored samples for hepcidin, transferrin and ferritin will be blinded to whether the
sample is from a participant who developed active TB during follow-up, or from a cohort
participant who did not.
The study will recruit 1515 trial participants each at Stellenbosch University in South
Africa, 1515 at Centro de Investigação em Saúde de Manhiça in Mozambique and 1010 at Makerere
University in Uganda. Participants will be between the ages of 12 and 60 years; pregnant
women, minorities, economic and education disadvantaged, both HIV negative and positive will
join the study. Contacts found to have co-prevalent active TB, potential pathologies on CXR,
abnormal Hb and CRP levels will be referred to the local clinic for investigation per
standard-of-care with a written summary of the relevant study results. All participant
information will be treated in a strictly confidential manner and will be identified only by
a code and not by any personal identifier.
PreFIT's results will contribute to the development and uptake of accurate, cost-effective,
scalable and field-friendly diagnostic tools, to facilitate scale-up of preventive treatment
in sub-Saharan Africa and beyond.
