Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Accuracy and Consequences of Using Trial-of-antibiotics for TB Diagnosis (ACT-TB Study) (ACT-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: NCT03545373
Recruitment Status : Recruiting
First Posted : June 4, 2018
Last Update Posted : August 15, 2019
Sponsor:
Collaborator:
University of Malawi College of Medicine
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Brief Summary:
This is a three-arm, open-label individually randomised controlled clinical trial investigating the benefits of the diagnostic use of broad-spectrum antimicrobials during the diagnostic process for tuberculosis (TB) and the risk of antimicrobial resistance. 1875 adults (≥18 years) presenting to primary care with TB symptoms will, after excluding acute illness, be randomised (1:1:1) to receiving azithromycin, amoxicillin or standard care. Diagnostic accuracy will be ascertained by comparing self-reported response to treatment on Day-8 to results of mycobacteriology tests (MTB culture, smear microscopy and Xpert/MTB/RIF). Antimicrobial resistance will be ascertained by comparing arms with respect to incidence of resistant Streptococcus pneumonia carriage cultured from nasopharyngeal swabs collected on Day-28. Clinical benefit will be ascertained by comparing clinical outcomes by Day-29.

Condition or disease Intervention/treatment Phase
Tuberculosis Respiratory Tract Infections Pneumonia Drug: Azithromycin Drug: Amoxicillin Phase 3

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1875 participants
Allocation: Randomized
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.
Primary Purpose: Diagnostic
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Azithromycin
Azithromycin 500mg, oral, once daily for 3 days commencing on randomization day.
Drug: Azithromycin
Azithromycin tablet taken orally

Experimental: Amoxicillin
Amoxicillin 1g, oral, 3 times daily for 5 days commencing on randomization day.
Drug: Amoxicillin
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)



Primary Outcome Measures :
  1. 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.


  2. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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:

    1. Incremental cost per quality adjusted life year gained
    2. Total direct medical costs per participant
    3. Eq-5D utility score



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:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ambulatory clinic attendees presenting with cough for at least 14 days
  • Aged at least 18 years
  • Reside in Blantyre and willing to return to the same clinic for follow up visits over the entire study period.

Exclusion Criteria:

  • Self-reported allergy to study medications
  • Danger signs (WHO/Malawi National TB Program):

respiratory rate > 30/min, temperature >39oC, Heart rate >120/minute, confused/agitated, respiratory distress, systolic blood pressure <90 mmHg, inability to walk unassisted

  • Treated with antibiotics other than co-trimoxazole prophylaxis, for the current illness or within the past 14 days
  • Tuberculosis treatment or isoniazid preventive therapy in the last 6 months

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): NCT03545373


Contacts
Layout table for location contacts
Contact: Titus H Divala, MBBS MPH MS + 447405231847 titus.divala@lshtm.ac.uk
Contact: Katherine L Fielding, BSc MSc PhD +442079272889 Katherine.Fielding@lshtm.ac.uk

Locations
Layout table for location information
Malawi
University of Malawi College of Medicine Recruiting
Blantyre, Southern, Malawi, 00265
Contact: Titus H Divala, MBBS    +265996891479    ckandulu@gmail.com   
Contact: Chikondi Kandulu, MBBS         
Principal Investigator: Titus H Divala, MBBS         
Sub-Investigator: Elizabeth E Corbett         
Sub-Investigator: Chikondi Kandulu         
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
University of Malawi College of Medicine
Investigators
Layout table for investigator information
Principal Investigator: Titus H Divala, MBBS MPH MS London School of Hygiene and Tropical Medicine

Layout table for additonal information
Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT03545373     History of Changes
Other Study ID Numbers: 15232
First Posted: June 4, 2018    Key Record Dates
Last Update Posted: August 15, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Data sharing of all data with any group requesting access to individual records will be ensured within 12 months of completion of publication related analyses, with all data and study tools made available by that time through the institutional research data repository established by London School of Hygiene & Tropical Medicine(LSHTM) Research Data Management Support Service..

Anonymised data will be held for sharing as original databases stored with a soft copy of the fully annotated questionnaires and the STATA files used for recoding and analysis. Personal identifiers, such as names, will not be held, with ID numbers used instead.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: After publishing study main papers.
Access Criteria: Through the London School of Hygiene & Tropical Medicine data repository.

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 London School of Hygiene and Tropical Medicine:
antimicrobial resistance
TB
Cough
antibiotics
anti-infective agents

Additional relevant MeSH terms:
Layout table for MeSH terms
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Tuberculosis
Respiratory Tract Infections
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Infection
Amoxicillin