Back to resultsRapid Research in Diagnostics Development for TB Network (R2D2 Kids) and Assessing Diagnostics At POC for TB in Children (ADAPT for Kids)
Primary Purpose
Tuberculosis, Diagnostics, Global Health
Status
Not yet recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Oral swab molecular testing
Automated Cough Sound Analysis
Automated Lung Sound Analysis
Chest X Ray Computer Aided Detection
Sponsored by
About this trial
This is an interventional diagnostic trial for Tuberculosis
Eligibility Criteria
Participant eligibility criteria: Participants will include children (age <15 years) who present to care with: A. 2 or more of the following: Unexplained cough for any duration TB contact or tuberculin skin test or interferon gamma release assay positive Abnormal chest X-ray (any abnormality) OR B. Any one of criteria A AND any one of the following: Unexplained weight loss OR unexplained failure to thrive OR Severe Acute Malnutrition Unexplained fever ≥2 weeks Unexplained lethargy or reduced playfulness ≥2 weeks The study will exclude participants who: Completed preventive or active TB treatment within the past 12 months (to increase TB prevalence and reduce false-positive results, respectively); Have taken any medication with anti-mycobacterial activity for any reason for greater than 3 days at the time of enrollment (to reduce false-negatives); Are unable to return for follow-up visits; or Whose parents/guardians are unwilling to provide informed consent or who are unwilling to provide assent if applicable (age determined by local IRB) Assessment of the usability of novel TB tests: The study will also include health workers at each clinical site who are 1) aged ≥18 years and 2) involved in routine TB testing (collecting specimens for or performing TB tests). Personnel who are unwilling to provide informed consent will be excluded.
Sites / Locations
- Instituto Nacional de Saúde
- Dora Nginza Hospital
- Mulago National Referral Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Evaluation of various novel TB triage and diagnostic tests
Arm Description
The investigators will conduct evaluation of novel TB triage and diagnostic tests in a cohort of children with presumed TB. The investigators aim to enroll 250 participants per year at each of three enrollment sites for evaluation of various novel TB triage and diagnostic tests and 30 health workers to assess test usability. Novel test evaluations will be conducted on a rolling basis as new tests ready for field evaluation are identified.
Outcomes
Primary Outcome Measures
Proportion with positive index test result among participants with tuberculosis (TB)
Sensitivity - Number with positive index test result/(Number with positive or negative index t test result) among participants with TB. TB will be defined based on a microbiological reference standard (sputum mycobacterial culture results)
Proportion with negative index test result among participants without tuberculosis (TB)
Specificity - Number with negative index test results/(Number with positive or negative index t test result) among participants without TB. TB will be defined based on a microbiological reference standard (sputum mycobacterial culture results)
Secondary Outcome Measures
Full Information
NCT ID
NCT05989802
First Posted
July 28, 2023
Last Updated
August 9, 2023
Sponsor
University of California, San Francisco
Collaborators
Instituto Nacional de Saúde, Mozambique, National Referral Hospital, University of Cape Town, Johns Hopkins University, Elizabeth Glaser Pediatric AIDS Foundation, National Institute of Allergy and Infectious Diseases (NIAID), University of California, Irvine
1. Study Identification
Unique Protocol Identification Number
NCT05989802
Brief Title
Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and Assessing Diagnostics At POC for TB in Children (ADAPT for Kids)
Official Title
Rapid Research in Diagnostics Development for Tuberculosis Network (R2D2 Kids) and Assessing Diagnostics At Point-of-care for Tuberculosis in Children (ADAPT for Kids)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 1, 2023 (Anticipated)
Primary Completion Date
September 1, 2026 (Anticipated)
Study Completion Date
September 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Instituto Nacional de Saúde, Mozambique, National Referral Hospital, University of Cape Town, Johns Hopkins University, Elizabeth Glaser Pediatric AIDS Foundation, National Institute of Allergy and Infectious Diseases (NIAID), University of California, Irvine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
Every year there are an estimated 230,000 childhood deaths from TB. There is an urgent need for novel tests for TB diagnosis in children under 15 years. The Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and the Assessing Diagnostics at Point-of-care for Tuberculosis in children (ADAPT for Kids) studies seek to reduce the burden of TB worldwide by evaluating faster, simpler, and less expensive TB triage and diagnostic tests for use in children.
Detailed Description
The Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and the Assessing Diagnostics at Point-of-care for Tuberculosis in children (ADAPT for Kids) studies will rigorously assess promising, point-of-care (POC) TB diagnostic tests in clinical studies conducted among children at settings of intended use. There is an urgent need for novel tests for TB diagnosis in children under 15 years because of the challenge of obtaining sputum samples from children and the low sputum bacillary burden among children with TB even when a sample is obtained. This creates delays in diagnosis and treatment initiation, and is a major contributor to the 230,000 childhood deaths from TB each year. Therefore, a non-sputum biomarker-based test has been ranked among the highest priority target product profiles for new TB diagnostics. If inexpensive and simple to perform, such a diagnostic tool could have significant impact by facilitating rapid diagnosis and TB treatment in children. The studies will evaluate the sensitivity and specificity of novel diagnostic tests in children in reference to NIH consensus definitions for childhood TB. In addition, the usability and acceptability of the novel TB diagnostic tests will be assessed through direct observations and surveys of routine health workers.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Diagnostics, Global Health
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Evaluation of various novel TB triage and diagnostic tests
Arm Type
Experimental
Arm Description
The investigators will conduct evaluation of novel TB triage and diagnostic tests in a cohort of children with presumed TB. The investigators aim to enroll 250 participants per year at each of three enrollment sites for evaluation of various novel TB triage and diagnostic tests and 30 health workers to assess test usability. Novel test evaluations will be conducted on a rolling basis as new tests ready for field evaluation are identified.
Intervention Type
Diagnostic Test
Intervention Name(s)
Oral swab molecular testing
Intervention Description
Swab-based testing provides a non-invasive approach to collect respiratory specimens for TB testing. Data in adults suggests that swab-based testing could be valuable when sputum collection is not feasible or available.
Intervention Type
Diagnostic Test
Intervention Name(s)
Automated Cough Sound Analysis
Intervention Description
Cough sounds can be collected through a mobile phone and tablet, and then analyzed with machine learning algorithms to predict TB.
Intervention Type
Diagnostic Test
Intervention Name(s)
Automated Lung Sound Analysis
Intervention Description
Lung sounds can be collected with a non-invasive digital stethoscope, and then saved on a tablet or phone and analyzed by machine learning algorithms to predict TB.
Intervention Type
Other
Intervention Name(s)
Chest X Ray Computer Aided Detection
Other Intervention Name(s)
Artificial Intelligence algorithm
Intervention Description
Several artificial intelligence algorithms have been developed to predict TB, though this has not yet been validated in children.
Primary Outcome Measure Information:
Title
Proportion with positive index test result among participants with tuberculosis (TB)
Description
Sensitivity - Number with positive index test result/(Number with positive or negative index t test result) among participants with TB. TB will be defined based on a microbiological reference standard (sputum mycobacterial culture results)
Time Frame
2 years
Title
Proportion with negative index test result among participants without tuberculosis (TB)
Description
Specificity - Number with negative index test results/(Number with positive or negative index t test result) among participants without TB. TB will be defined based on a microbiological reference standard (sputum mycobacterial culture results)
Time Frame
2 years
10. Eligibility
Sex
All
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Participant eligibility criteria:
Participants will include children (age <15 years) who present to care with:
A. 2 or more of the following:
Unexplained cough for any duration
TB contact or tuberculin skin test or interferon gamma release assay positive
Abnormal chest X-ray (any abnormality) OR
B. Any one of criteria A AND any one of the following:
Unexplained weight loss OR unexplained failure to thrive OR Severe Acute Malnutrition
Unexplained fever ≥2 weeks
Unexplained lethargy or reduced playfulness ≥2 weeks
The study will exclude participants who:
Completed preventive or active TB treatment within the past 12 months (to increase TB prevalence and reduce false-positive results, respectively);
Have taken any medication with anti-mycobacterial activity for any reason for greater than 3 days at the time of enrollment (to reduce false-negatives);
Are unable to return for follow-up visits; or
Whose parents/guardians are unwilling to provide informed consent or who are unwilling to provide assent if applicable (age determined by local IRB)
Assessment of the usability of novel TB tests:
The study will also include health workers at each clinical site who are 1) aged ≥18 years and 2) involved in routine TB testing (collecting specimens for or performing TB tests). Personnel who are unwilling to provide informed consent will be excluded.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Devan Jaganath, MD
Phone
415-514-4692
Email
devan.jaganath@ucsf.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Brittney Sweetser, MPH
Email
bsweetse@hs.uci.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adithya Cattamanchi, MD, MAS
Organizational Affiliation
University of California, Irvine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nilesh Bhatt
Organizational Affiliation
Elizabeth Glazer Pediatric AIDS Foundation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto Nacional de Saúde
City
Maputo
Country
Mozambique
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Celso Khosa
Email
celso.khosa@ins.gov.mz
Facility Name
Dora Nginza Hospital
City
Cape Town
Country
South Africa
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Zar
Email
heather.zar@uct.ac.za
Facility Name
Mulago National Referral Hospital
City
Kampala
Country
Uganda
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric Wobudeya
Email
ewobudeya@mujhu.org
12. IPD Sharing Statement
Plan to Share IPD
No
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Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and Assessing Diagnostics At POC for TB in Children (ADAPT for Kids)
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