An Open Cohort of Childhood Tuberculosis in Mbarara National Referral Hospital, Uganda

Tuberculosis Clinical Trial

Official title:

An Open Cohort of Childhood Tuberculosis in Mbarara National Referral Hospital, Uganda

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01422798
• Other study ID #: Epicentre/MBA/2011/TBKidcohort
• Status: Completed
• Phase: N/A
• First received: August 15, 2011
• Last updated: February 29, 2016
• Start date: April 2012
• Est. completion date: December 2014

Study information

• Verified date: February 2016
• Source: Epicentre
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Committee for the Protection of PersonnesUganda: National Council for Science and Technology
• Study type: Observational

Clinical Trial Summary

The aims at investigating how the diagnosis of Tuberculosis in children in a setting of high TB and HIV prevalence can be improved and to assess the treatment outcomes and tolerance of the new WHO recommended TB drug dosages.

Description:

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. The situation for children in this epidemic is complex because they are usually considered less infectious and therefore, not to represent an important public health problem. Uganda ranks among the countries with the highest TB burden with 330/100,000 person-year TB incidence. Up to 16% of new TB infections are estimated to occur in children. Diagnosis of childhood TB is usually based on exposure history and a set of clinical, radiological and biological signs that considered separately have rather low predictive values. There is no consensus on the optimal way to combine these signs. This is even more complex when the child is infected with HIV. The risk of TB infection and disease, and the TB clinical presentation depend on the child's age, the youngest being at highest risk. An important first step in improving the management of childhood TB is to better define the clinical and radiological characteristics of children with suspected TB at first presentation to a health service in an endemic setting; also to document the feasibility and tolerability of TB treatment in this age cohort. This initial descriptive study would help to pave the way for more rigorous studies evaluating novel diagnostics and conducting clinical trials on first and second line TB treatment in children, in the future.

The main objective of the study is to improve the diagnosis of TB in children in a setting of high TB and HIV prevalence and to assess the treatment outcomes and tolerance of the new WHO recommended TB drug dosages.

The investigators will conduct an observational cohort study of paediatric TB suspects attending the Mbarara National Reference Hospital (MNRH). All included TB suspects will have an initial comprehensive assessment including clinical examination, chest X-ray, tuberculin skin test, smear microscopy, Mycobacterium tuberculosis culture, XpertMTB/RIF® of respiratory or extra-pulmonary specimen for diagnosis of tuberculosis. For children who cannot produce sputum, sputum induction will be proposed. Children with indication of TB treatment will be followed up to 6 months after completion of TB treatment (total 12 months) with treatment efficiency, tolerability and acceptability assessment. Children without indication of TB treatment will undergo a systematic clinical assessment after 3 months. Finally, clinical files from all TB suspects will be retrospectively reviewed by 2 independent paediatric TB experts in order to classify the cases as Confirmed TB, Certain TB, Probable TB and Unlikely TB cases. A total of 385 paediatric TB suspects (1 month-14 years) will be screened from the paediatric ward, OPD, HIV clinic of the MNRH, Holy Innocents children's hospital and The AIDS support organisation (TASO) in Mbarara.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 396
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 14 Years

Eligibility

Inclusion Criteria:

Any child with at least one of the following criteria:

• Unexplained weight loss or documented failure to thrive or stagnant weight or Growth faltering on the growth charts over the past 3 months despite adequate nutrition and deworming,

• Non - remittent cough or wheeze for more than 2 weeks,

• Night sweats persistent or intermittent during the last 2 weeks

• Prolonged fever (temperature > 38°C) for 7 days, after common causes such malaria or pneumonia has been excluded.

• Wheeze/Stridor - persistent, non remitting during the last 2 weeks

• Chest pain - Persistent, localized, pleuritic in nature during the last 2 weeks

• Unexplained fatigue, weakness, apathy, lethargy or reduced playfulness during the last 2 weeks

• Painless superficial lymph node mass (>2x2cm)-

• Chronic onset meningitis (>5days), lymphocytic predominance in CSF or meningitis not responding to antibiotic treatment (ref 8)

• Recent gibbus

• Abdominal distention with ascites OR

• Any child with an abnormal chest X-ray (CXR) suggestive of TB (hilar/paratracheal adenopathy with/without airway compression, airspace opacification not responding to antibiotics or documented TB contact, lung cavities or miliary infiltrates) OR

• Asymptomatic child with a history of recent contact (within past year) with a pulmonary TB smear or culture positive patient and an abnormal chest X-ray AND

• Informed Consent signed by parent or legal representative

Exclusion Criteria:

• Current TB treatment (patient who received < 3 days of treatment or patients receiving IPT could be still included) or TB treatment completed within the past 6 months.

• Absence of informed consent

• Living outside of Greater Mbarara region.

• Unable or unwilling to attend to the follow-up visits

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Tuberculosis

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Epicentre	Mbarara University of Science and Technology, Medecins Sans Frontieres

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of confirmed, certain, probable and unlikely TB cases among TB suspects		Week 48	No
Secondary	Baseline clinical presentation of TB suspects	Baseline clinical presentation of TB suspects: overall, among sub-groups of children defined by HIV infection, malnutrition, age category (<3 years, 3-10 years and > 10 years), TB treatment decision and according to the TB classification using the proxy reference standard	Week 12 and 24	No
Secondary	Baseline biological characteristics (smear microscopy, culture and XpertMTB/RIF® of sputum and other specimen for EPTB suspects) of TB suspects	Baseline biological characteristics (smear microscopy, culture and XpertMTB/RIF® of sputum and other specimen for EPTB suspects) of TB suspects: overall, among sub-groups of children defined by HIV infection, age category (<3 years, 3-10 years and > 10 years), TB treatment decision and disease classification	Week 12 and 24	No
Secondary	XpertMTB/RIF® and culture results in stools of TB suspects		Week 12 and 24	No
Secondary	Number of children started on TB treatment among TB suspects		Week 24	No
Secondary	Number of TB suspect cases who were initially diagnosed as non TB who died or eventually received a TB diagnosis within the first 3 months of clinical follow-up		Week 12	No
Secondary	Treatment successes (cured and completed), failures, defaulters and deaths		Week 48	No
Secondary	TB recurrence 6 months after completion of TB treatment		Week 48	No
Secondary	Antiretroviral treatment (ART) regimen and time to initiation in co-infected children		Week 48	No
Secondary	Occurrence and clinical description of IRIS episodes		Within 2 months of ART initiation	No
Secondary	Type and frequency of grade 3 and 4 adverse events during TB treatment, with/without concomitant ART		Week 2, 4, 8, 16, 24	No
Secondary	Pill burden, adherence rate and drugs errors with the use of new paediatric dosages		Week 2, 4, 6, 8, 12, 16, 20, 24	No