Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 14 for:    RAPID AND children | TB
Previous Study | Return to List | Next Study

Rapid and Accurate Diagnosis of Paediatric (RaPaed) TB - An AIDA (Assessment of Innovative Diagnostics and Algorithms for Early and Sensitive Detection of Acute TB) Platform Study (RaPaed-AIDA-TB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03734172
Recruitment Status : Recruiting
First Posted : November 7, 2018
Last Update Posted : May 9, 2019
Sponsor:
Collaborators:
University of Cape Town Lung Institute
Instituto Nacional de Saúde, Mozambique
University of Malawi College of Medicine
Karolinska Institutet
Research Center Borstel
University of Stellenbosch
Beckman Coulter, Inc.
Cepheid
Otsuka Novel Products GmbH
University of Melbourne
Foundation for Innovative New Diagnostics, Switzerland
National Institute for Medical Research, Tanzania
Information provided by (Responsible Party):
Michael Hoelscher, Ludwig-Maximilians - University of Munich

Brief Summary:

This study will serve as a platform to evaluate new diagnostics in children suspected to have TB, to establish diagnostic performance (sensitivity and specificity) and calculation of positive and negative predictive values in a real-life cohort.

Finally, this study will comprise results of several tests in its database. This will allow simulation of diagnostic algorithms, that may be composed of screening (i.e. rule-out) tests together with confirmatory tests to maximize sensitivity and specificity.


Condition or disease Intervention/treatment
Tuberculosis Diagnoses Disease Diagnostic Test: Sample collection

Layout table for study information
Study Type : Observational
Estimated Enrollment : 800 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Rapid and Accurate Diagnosis of Paediatric (RaPaed) TB - An AIDA (Assessment of Innovative Diagnostics and Algorithms for Early and Sensitive Detection of Acute TB) Platform Study
Actual Study Start Date : January 21, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Paediatric diagnostic group
Paediatric diagnostic group
Diagnostic Test: Sample collection
Specimen collection




Primary Outcome Measures :
  1. Sensitivity and Specificit of new test candidates; against a clinica/microbiological reference standard case definition [ Time Frame: 6 months ]

    The case definition has been defined by an NIH-convened expert panel, published in 2012 and updated in 2015 (S. Graham et al.; CID). This definition describes the diagnostic certainty for a child to suffer from TB.

    Possible classifications:

    • Confirmed active tuberculosis
    • Unconfirmed tuberculosis
    • Unlikely tuberculosis

    This case definition will be made based on the following:

    • Confirmed active tuberculosis: bacteriological confirmation obtained (TB lab; positive culture AND/OR WHO endorsed PCR).
    • Unconfirmed tuberculosis: bacteriological confirmation NOT obtained AND at least two of the following:

    Symptoms suggestive of TB X-ray suggestive of TB Close exposure to TB Positive response to TB treatment

    • Unlikely tuberculosis: defined as bacteriological confirmation NOT obtained AND criteria for "unconfirmed tuberculosis" NOT met



Other Outcome Measures:
  1. Ability of new tests to measure response to TB treatment, by measuring the change in experimental test readout over time while receiving TB treatment [ Time Frame: 6 months ]
    Rate of change of new test readout (e.g. antigen detection rates), in children who receive TB treatment

  2. Proportion of children with confirmed TB, and with other diseases, who have acute and chronic lung impairment using spirometry [ Time Frame: 12 months ]
    Spirometry parameters: forced vital capacity (FVC) in l; forced expiratory volume in 1 second (FEV 1)


Biospecimen Retention:   Samples With DNA
Molecular speciation test; Mycobacterial DNA extraction will be performed centrally on stored samples and will be further analysed using classical molecular MTB typing methods (genotyping) as well as by next generation sequencing (genome sequencing).


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 14 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients 14 years old or younger with a suspicion of active TB are eligible for recruitment into the study, if they meet the specified inclusion criteria, and none of the exclusion criteria.
Criteria

Inclusion Criteria:

  1. Consent and Assent (if applicable): signed written consent/assent, or witnessed oral consent/assent in the case of illiteracy, before undertaking any study-specific activity. The age threshold for child assent requirement will be laid down in each the Investigator Site File based on the local Ethics Committee requirement.

    Of the following, either criterion 2), OR criterion 3), or both, have to be met:

  2. Confirmation of TB disease: microbiological confirmation of active TB disease by positive smear AND/OR culture AND/OR PCR (e.g. GeneXpert®); e.g. in a non-study health facility AND/OR
  3. Signs and Symptoms: suspicion of active TB disease (one or more criteria):

    1. Chest X-ray suggestive of TB: cavity AND/OR hilar/mediastinal lymph node enlarged AND/OR military pattern
    2. Weight loss or failure to thrive within the previous 3 months that, in the investigator's opinion, is not solely due to inadequate feeding; or to another non-TB cause.
    3. Any cough combined with loss of weight
    4. Cough alone: duration of > 14 days
    5. Repeated episodes of fever within 14 days not responding to course of antibiotics AND positive TST or IGRA, (for malaria endemic areas: AND after malaria has been excluded by at least a negative rapid test)*
    6. Signs & symptoms of extrapulmonary TB:

      • Enlarged lymph nodes for > 2 weeks, not painful to palpation;
      • Gibbus (especially of recent onset)
      • Non-painful enlarged joint
      • Pleural effusion
      • Pericardial effusion
    7. CSF examination findings in line with TB meningitis with at least elevated protein and low glucose (in relation to serum glucose); OR signs and symptoms in line with TB meningitis/CNS TB if lumbar puncture is contraindicated, in the view of the investigator:

At least one of the following two:

  • palsy of oculomotoric nerves of recent onset
  • focal neurological symptoms indicating elevated intracranial pressure OR CNS lesions, of recent onset

AND/OR at least two of the following less specific signs of TB meningitis/CNS TB (for malaria endemic areas: AND a negative malaria rapid diagnostic test*):

  • Lethargy
  • Convulsion
  • Meningism (neck stiffness)
  • Headache (*the requirement of negative MRDT may be dropped in agreement with the sponsor during study conduct.)

Exclusion Criteria:

  1. Critical condition (if study procedures seems like an undue risk to patient's life), such as hypovolemic shock or clinically relevant anaemia (tachypnoea, tachycardia)
  2. Body weight is less than 2 kg
  3. Children of 15 years of age or older
  4. Are currently receiving anti-TB drug(s): ideally, eligible patients should not have received any anti-TB treatment. In exceptions, up to three daily doses given since treatment start before first study blood draw are acceptable for study inclusion

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03734172


Contacts
Layout table for location contacts
Contact: Norbert Heinrich, MD +49 89 440059805 aida@lrz.uni-muenchen.de
Contact: Laura Olbrich, MD +49 89 440059803 aida@lrz.uni-muenchen.de

Locations
Layout table for location information
Malawi
University of Malawi College of Medicine Recruiting
Blantyre, Malawi
Contact: Marriott Nliwasa, PhD    +265 88 8681948    mnliwasa@gmail.com   
Contact: Robina Semphere    +265 997204626    robinasemphere@gmail.com   
Mozambique
Centro de Investigação e Treino em Saúde da Polana Caniço Recruiting
Maputo, Mozambique, PO.BOX 264
Contact: Celso Khosa, MD    +258-82-28893130    khosacelso@gmail.com   
Contact: Denise 0 Banze    +258-21-82-28893130    den.floripes@gmail.com   
Principal Investigator: Nilesh Bhatt, MD, MMED         
Sub-Investigator: Celso Khosa, MD         
South Africa
University of Cape Town Lung Institute (UCTLI) Recruiting
Cape Town, Cape, South Africa
Contact: Heather J Zar, Professor    +27 21 6585324    heather.zar@uct.ac.za   
Tanzania
NIMR - Mbeya Medical Research Programme Recruiting
Mbeya, Tanzania, P.O. Box 2410
Contact: Nyanda Ntinginya, MD, PhD    00255 25 250 ext 2239      
Principal Investigator: Nyanda E Ntinginya, MD         
Sponsors and Collaborators
Michael Hoelscher
University of Cape Town Lung Institute
Instituto Nacional de Saúde, Mozambique
University of Malawi College of Medicine
Karolinska Institutet
Research Center Borstel
University of Stellenbosch
Beckman Coulter, Inc.
Cepheid
Otsuka Novel Products GmbH
University of Melbourne
Foundation for Innovative New Diagnostics, Switzerland
National Institute for Medical Research, Tanzania
Investigators
Layout table for investigator information
Principal Investigator: Michael Hoelscher, Professor University Hospital, LMU Munich
Study Director: Norbert Heinrich, MD University Hospital, LMU Munich

Layout table for additonal information
Responsible Party: Michael Hoelscher, Prof Dr med / Sponsor Responsible Person, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT03734172     History of Changes
Other Study ID Numbers: LMU-IMPH-AIDA-02
First Posted: November 7, 2018    Key Record Dates
Last Update Posted: May 9, 2019
Last Verified: May 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michael Hoelscher, Ludwig-Maximilians - University of Munich:
Tuberculosis
Paediatrics
Diagnostics
Additional relevant MeSH terms:
Layout table for MeSH terms
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections