Project Title: Impact of a point of care C-reactive protein assay used as as triage test on diagnostic yield in tuberculosis screening among outpatients in Tanzania; a pragmatic cluster randomized trial
Project Description: The current TB symptom screening has acceptable sensitivity but low specificity particularly in HIV-positive patients. Furthermore, symptom screening depends on the skills and clinical acumen of an attending clinician and most often is not fully implemented. Due to its low specificity symptom screening potentially leads to more confirmatory tests than what would be logistically and economically feasible. C-reactive protein (CRP), which is already available as an inexpensive, routinely used test, has great potential for point... The current TB symptom screening has acceptable sensitivity but low specificity particularly in HIV-positive patients. Furthermore, symptom screening depends on the skills and clinical acumen of an attending clinician and most often is not fully implemented. Due to its low specificity symptom screening potentially leads to more confirmatory tests than what would be logistically and economically feasible. C-reactive protein (CRP), which is already available as an inexpensive, routinely used test, has great potential for point The current TB symptom screening has acceptable sensitivity but low specificity particularly in HIV-positive patients. Furthermore, symptom screening depends on the skills and clinical acumen of an attending clinician and most often is not fully implemented. Due to its low specificity symptom screening potentially leads to more confirmatory tests than what would be logistically and economically feasible. C-reactive protein (CRP), which is already available as an inexpensive, routinely used test, has great potential for point of care triaging before TB confirmation due to its good sensitivity and specificity for detection of TB. Hence, CRP might have the potential to become a cost-effective triage test at lowers levels of the health care system before a follow-on TB diagnostic. We will assess the impact of CRP as a point of care triage test on patient-important outcomes and diagnostic yield in primary healthcare facilities in comparison to the current practice of TB symptom screening. Project Aims Our overall goal is to assess the impact of CRP as a point of care triage test on patient-important outcomes and diagnostic yield in primary health care facilities in comparison to the current practice of TB symptom screening. Primary endpoints The proportion of participants who have bacteriologically confirmed TB and have TB therapy initiated within 7 days of enrolment Additionally, diagnosed cases in the intervention compared to the standard of care Settings Secondary endpoints Outcomes-based only on microbiological diagnosis • Proportion of participants completing testing with microbiological tests • Proportion diagnosed with microbiologically confirmed TB • Time to treatment initiation based on microbiologically confirmed TB diagnosis • Proportion of participants who have bacteriologically confirmed TB and have TB therapy initiated within 14, 60 days / 180 days of enrolment (i.e. primary outcome at additional time points) Outcomes-based on both microbiological and clinical diagnosis • Proportion diagnosed with TB (either microbiologically or clinically) • Time to TB treatment initiation based on either microbiologically or clinically diagnosed TB • Proportion of participants who have TB therapy initiated within 7 days / 60 days / 180 days of enrolment (based on microbiologically or clinically diagnosed TB) Death or pre-treatment LTFU at 180 days (i.e. combined as a composite outcome as well as reported separately) Death or overall LTFU at 180 days (i.e. combined as a composite outcome as well as reported separately) Sensitivity and specificity of CRP Study population Adults attending an outpatient clinic in primary healthcare facilities in Tanzania; Kimara, Mburahati, Mbezi, Mbagala Kizuiani, Sandali, Buza, Mbagala maji matitu, Tambuka reli, Mtoni, Yombo vituka, Pande, Miono, Ubena estate, St Elizabeth. Project Design This study has two parts A and B Part A: Pre-study, the accuracy of CRP A prospective accuracy study among adults attending outpatient clinics at Mbagala Kizuiani dispensary will be conducted. Here the index test is C reactive protein (CRP) a non-specific point of care test which has been shown to have significant value in TB detection. We will use the cut-off point of 10mg/l (positive test) similar to previous studies. We will measure CRP concentrations using whole blood by finger pricking. CRP results will not be used for the decision to treat. Reference test We will use GeneXpert MTB/RIF as a reference test. A four-module GeneXpert MTB/RIF (Xpert) will be installed at Tegeta dispensary. We will collect one spot sample of sufficient volume of sputum (5ml) for Xpert testing. TB suspects who were not diagnosed with TB will be contacted at two months to establish whether there are any new TB diagnosis made and their well-being. Part B: Impact of CRP Triage test A pragmatic, prospective, two-arm, cluster randomized controlled trial in urban, semi-urban, and rural in Tanzania using primary health facilities as units of randomization, to evaluate the impact of the CRP triage test for TB on diagnostic yield among outpatients in primary healthcare facilities. Study procedures Health facilities will be assigned to either the intervention (CRP triage test) or the control (symptom screening). All patients in the intervention arm attending outpatient and with any symptom of any duration (cough, fever, night sweats, weight loss, hemoptysis, or fatigue) of TB will be screened using CRP test. CRP positive patients will be tested for TB using the available confirmatory test, which is in the majority of cases smear microscopy and rarely Xpert MTB/RIF. Patients in the control arm will be screened using the TB symptom screening tool as per standard of care (prolonged cough of 2 weeks duration and above and any one of the following symptoms; fever, night sweats, loss of weight, hemoptysis or fatigue). Primary healthcare facilities will record demographics in the trial suspect log. Dedicated trial personnel will visit each facility on weekly basis and record the required variables from the suspect log, the laboratory register, and the TB registers. For all participants, a phone call at 6 months after enrolment will be made to establish if the participant is alive or deceased, and if and when TB treatment and ART has been started (start dates). If three attempts to reach the participant on three different days have failed, a participant-nominated contact person will be called to find out if the participant is alive or dead. Dedicated trial personnel will trace information in TB registers for all participants reporting to have started TB treatment.
Principal Investigator : Jerry Hella
Department Name :
Time frame: (2019-11-15) - (2024-03-31)
Swiss Tropical and Public Health Institute (Normal)
External Collaborating Partners
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