Accuracy and Consequences of Using Trial-of-antibiotics for TB Diagnosis (ACT-TB Study) (ACT-TB)
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|ClinicalTrials.gov Identifier: NCT03545373|
Recruitment Status : Recruiting
First Posted : June 4, 2018
Last Update Posted : August 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Tuberculosis Respiratory Tract Infections Pneumonia||Drug: Azithromycin Drug: Amoxicillin||Phase 3|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1875 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Three treatment arms allocated using computer generated block randomization in a 1:1:1 ratio.|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||All laboratory forms for mycobacteriology and nasopharyngeal pneumococcal work will have no reference to participant treatment allocation. On Day-8, assessment of improvement from baseline symptoms will utilize audio computer-assisted self-interview (ACASI) to minimise potential for social-mediated reporting and ascertainment biases. On Day-29, clinical outcome assessment forms will bear no reference to treatment arm. Participants, research coordinators, and routine care staff will not be masked to ensure safety of the participants and allow appropriate patient management decision-making which may be related to the trial interventions.|
|Official Title:||Randomised Controlled Clinical Trial Investigating Benefits of Using Response to Broad Spectrum Antibiotics as an Exclusion Diagnostic for Tuberculosis (TB) in Primary Care Adult Patients Versus Risk of Antimicrobial Resistance (AMR)|
|Actual Study Start Date :||February 25, 2019|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||June 2020|
Azithromycin 500mg, oral, once daily for 3 days commencing on randomization day.
Azithromycin tablet taken orally
Amoxicillin 1g, oral, 3 times daily for 5 days commencing on randomization day.
Amoxicillin tablets taken orally
No Intervention: Standard of care
The standard of care in current national guidelines for patients presenting with cough and without danger signs (No treatment, re-evaluate with sputum results)
- Diagnostic accuracy of trial-of-antibiotics: Proportion of participants correctly classified as PTB negative based on report of improvement of baseline symptoms on study Day-8 against a mycobacteriology reference standard. [ Time Frame: Day 1 to Day 8 ]
To minimise ascertainment bias evaluation of improvement of baseline symptoms will be captured using Audio Computer Assisted Self-Interview (ACASI). After orientation, the participant will be left alone in the room to interact with the computer. ACASI on Day-8 will precede all other interaction with research staff and clinical assessment/decision making.
Mycobacteriology reference standard will be defined in participants with at least one specimen with a valid result on days 1 and 8 as:
TB-POSITIVE: if at least one positive smear microscopy, Xpert/MTB/RIF, or MTB culture on sputum samples taken.
TB-NEGATIVE: none of the day 1 and day 8 sputum samples are positive on smear microscopy, GeneXpert MTB/RIF, or MTB culture.
The responses of participants during the ACASI interview will be classified as:
TB-POSITIVE: participant reports lack of improvement of symptoms they had on Day 1.
TB-NEGATIVE: participant reports improvement of symptoms they had on Day 1.
- Overall clinical benefit of empirical antibiotic treatment in primary care participants with chronic cough: proportion of participants experiencing adverse clinical outcomes [ Time Frame: Day 1 to Day 29 ]Cumulative incidence of adverse clinical outcomes defined as at least one of 1)death, 2)hospitalisation, 3)missed TB diagnosis, 4)HIV care loss to follow up and 5)TB care loss to follow up
- Impact of trial-of-antibiotics on antimicrobial resistance [ Time Frame: Day 1 to Day 29 ]Incidence of nasopharyngeal Streptococcus pneumonia isolates resistant to any of the commonly used groups of antimicrobials on Day-29.
- Diagnostic accuracy of trial-of-antibiotics including participants who did not produce sputum [ Time Frame: Day 1 to Day 8 ]Proportion of participants correctly classified as PTB negative based on report of improvement of baseline symptoms on study Day-8 (i.e. after a trial-of-antibiotics if in azithromycin or amoxicillin arms, or without antibiotics if in standard of care arm) against a mycobacteriology reference standard, among all randomised participants, with those who could not provide sputum classified as mycobacteriologically negative.
- Economic analysis of use of trial-of-antibiotics [ Time Frame: Day 1 to Day 29 ]
To estimate the incremental cost-effectiveness of trial-of-antibiotics using azithromycin and trial-of-antibiotics using amoxicillin in comparison to standard of care, and to each other using a combination of information from the following data:
- Incremental cost per quality adjusted life year gained
- Total direct medical costs per participant
- Eq-5D utility score
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): NCT03545373
|Contact: Titus H Divala, MBBS MPH MS||+ email@example.com|
|Contact: Katherine L Fielding, BSc MSc PhD||+442079272889||Katherine.Fielding@lshtm.ac.uk|
|University of Malawi College of Medicine||Recruiting|
|Blantyre, Southern, Malawi, 00265|
|Contact: Titus H Divala, MBBS +265996891479 firstname.lastname@example.org|
|Contact: Chikondi Kandulu, MBBS|
|Principal Investigator: Titus H Divala, MBBS|
|Sub-Investigator: Elizabeth E Corbett|
|Sub-Investigator: Chikondi Kandulu|
|Principal Investigator:||Titus H Divala, MBBS MPH MS||London School of Hygiene and Tropical Medicine|