Validation of a Tuberculosis Treatment Decision Algorithm in HIV-infected Children (TB-Speed HIV)

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

278 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-02

Study Completion Date

2022-06-20

Brief Summary

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TB-Speed HIV is a prospective multicentre management study evaluating the safety and feasibility of the recently proposed PAANTHER TB treatment decision algorithm for HIV-infected children with presumptive TB. It will be conducted in four countries with high and very high TB (Tuberculosis) incidence (Côte d'Ivoire, Uganda, Mozambique, and Zambia) which have not participated in the study that developed the PAANTHER algorithm.

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Detailed Description

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The ANRS 12229 PAANTHER 01 (Pediatric Asian African Network for Tuberculosis and HIV Research) study, which enrolled 438 HIV-infected children of median age 7.3 (IQR: 3.3 - 9.7) years with presumptive TB in four countries (Burkina Faso, Cameroon, Cambodia, Vietnam) from 2011 to 2014, aimed at developing a diagnostic prediction score and algorithm for TB treatment decision in HIV-infected children. This was the first study developing a TB diagnostic score exclusively in HIV-infected children, using methods recommended for diagnostic prediction models. Based on microbiological, clinical and radiological features, the best scoring system obtained had a sensitivity of 88.6% and specificity of 61.2% when Xpert MTB/RIF was included in the algorithm. The investigators showed previously that mortality is high in children with both confirmed and unconfirmed TB and that initiation of anti-TB treatment, that occurred at a median time of 7 (IQR: 5 - 11) days in the study, led to delayed ART initiation, which is associated to significantly increased mortality. The score, based on easily collected clinical features, chest radiographic features, Xpert MTB/RIF results, and abdominal ultrasonography, could enable same-day TB treatment decision. Abdominal ultrasonography has shown promise for the diagnosis of TB in both HIV-infected adults and children. In the PAANTHER study, it detected abdominal lymphadenopathy in 50% of culture confirmed TB cases and 35% of all confirmed and unconfirmed cases, with a specificity of 85%.

Developed in tertiary research-experienced health facilities, the PAANTHER score could enable standardized treatment decision in HIV-infected children with presumptive TB, and could be recommended for extensive use in secondary and primary healthcare settings where most of these children are seeking care. However, external validation studies are now needed to assess the predictive performance of the PAANTHER diagnostic score on independent datasets.

The PAANTHER TB treatment decision algorithm will be used for a TB treatment decision by site clinicians in all children enrolled in the study. Validation of the algorithm will be performed by evaluating the safety of withholding TB treatment in children not initiated on treatment as per the PAANTHER TB treatment decision algorithm. The safety of this strategy will be carefully assessed through review of safety reports every 4 to 6 months during study conduct by the safety sub-committee of the SAB.

Occurrence of algorithm failures in terms of missed TB cases (TB cases subsequently detected among untreated cases, i.e. false negatives) and cases with unlikely TB among those initiated on TB treatment as per the algorithm (cases not secondarily validated as confirmed or unconfirmed TB cases by the expert committee, i.e. false positives) will enable to estimate the negative and positive predictive values of the algorithm.

A centralized international Expert Committee will clinically review and validate TB diagnosis in children. This will enable assessment of the added value of new markers (MLR and CRP) and, if need be, to propose a new version of the score based on an optimised predicted probability.

The TB-Speed HIV study will be implemented in 7 tertiary healthcare level hospitals in capital cities of Côte d'Ivoire, Uganda, Mozambique, and Zambia. A total of 550 HIV-infected children (aged \< 15 years) with clinically suspected TB (presumptive TB) will be enrolled, using standard entry criteria. The inclusion period will last until all sites have reached the expected number of children enrolled.

Conditions

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Tuberculosis HIV

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

TB-Speed HIV is a prospective, multicentre management study evaluating the safety and feasibility of the recently proposed PAANTHER TB treatment decision algorithm for HIV-infected children with presumptive TB.

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Interventions

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External validation of the PAANTHER TB treatment decision algorithm

The PAANTHER algorithm will be used for a TB treatment decision by site clinicians in all children enrolled in the study. The PAANTHER algorithm and prediction score was designed as a guiding tool for empirical TB treatment decision in HIV-infected children with presumptive TB. The proposed score includes:

* history of contact
* suggestive TB symptoms
* tachycardia
* chest radiography
* abdominal ultrasound
* Xpert MTB/RIF Ultra.

A score of \>100 is highly predictive of TB. In children with a score \>100, anti-TB treatment will be initiated immediately. In children with a score of \<100, TB treatment will not be initiated except in those with severe/life-threatening conditions for whom TB treatment decision could be made at the discretion of the site clinician. TB could be definitely ruled out after further assessment and decision made as to what treatment the children should receive in accordance with existing national protocols, along with clinical follow-up.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Children aged 1 month to 14 years
2. Documented HIV-infection (i.e., confirmed before entry into the study)
3. Presumptive TB based on at least one criteria among the following:

1. Persistent cough for more than 2 weeks
2. Persistent fever for more than 2 weeks
3. Recent failure to thrive (documented clear deviation from a previous growth trajectory in the last 3 months or Z score weight/age \< 2)
4. Failure of broad spectrum antibiotics for treatment of pneumonia
5. Suggestive CXR features

OR

History of contact with a TB case and any of the symptoms listed under point 3 with a shorter duration (\< 2 weeks)
4. Informed consent signed by parent/guardian

Minimum Eligible Age

1 Month

Maximum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No