Tuberculosis (TB) Aftermath

August 14, 2023 updated by: Johns Hopkins University

Tuberculosis (TB) Aftermath: a Hybrid Type I Effectiveness-implementation Non-inferiority Randomized Trial in India Comparing Two Active Case Finding (ACF) Strategies Among Individuals Treated for TB and Their Household Contacts

TB Aftermath will compare effectiveness, cost-effectiveness and feasibility of two ACF strategies for detecting recurrent TB and provide evidence needed to implement and scale the preferred ACF strategy. The specific aims are:

Primary Aim 1: To conduct a non-inferiority randomized trial to measure the comparative effectiveness of two potentially implementable ACF strategies within India's National TB Elimination Program (NTEP), conducted by existing NTEP healthcare workers (HCWs): (i) home-based ACF (HACF) and (ii) telephonic ACF (TACF).

Primary Aim 2: To characterize implementation processes of the ACF strategies using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to inform future scale-up and sustainability.

Primary Aim 3: To model the impact and cost effectiveness of the ACF strategies evaluated in the trial, and of potential alternative strategies for the targeting and timing of those strategies.

Secondary Aim: To measure the association of the severity, chronicity and progression of post-TB lung impairment with recurrent TB disease.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Approximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. The investigators will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and the household contacts (HHCs).

The investigators will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with the HHCs (averaging two per patient, n = 2152). Participants will undergo symptom-based ACF by existing healthcare workers (HCWs) at 6-month intervals and will be randomized to either home-based ACF (HACF) or telephonic ACF (TACF). Symptomatic participants will undergo microbiologic testing through the program. Asymptomatic HHCs will be referred for TB preventive treatment (TPT) per national guidelines. The primary outcome is rate per 100 person-years of people diagnosed with new or recurrent TB by study arm, within 12 months following treatment completion. The secondary outcome is proportion of HHCs < 6 years, by study arm, initiated on TPT after ruling out TB disease. Study staff will collect socio-demographic and clinical data to identify risk factors for TB recurrence and will measure post-TB lung impairment. In both arms, an 18-month "mop-up" visit will be conducted to ascertain outcomes. The investigators will use the RE-AIM framework to characterize implementation processes and explore acceptability through in-depth interviews with index patients, HHCs and HCWs (n = 100). Cost-effectiveness will be assessed by calculating the incremental cost per TB case detected within 12 months and projected for disability-adjusted life years averted based on modeled estimates of morbidity, mortality, and time with infectious TB.

This novel trial will guide India's scale-up of post-treatment ACF and provide an evidence base for designing strategies to detect recurrent and new TB in other high burden settings.

Study Type

Interventional

Enrollment (Estimated)

3228

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • India
    • Maharashtra
      • Pune, Maharashtra, India, 411018

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Those who are registered at one of the study TB Units (TUs) in Pune district as treatment completed or cured (regardless of type of TB or duration of treatment).
  • Confirmed treatment completion or cure status by the referring medical officer of the study TU.
  • Date of treatment completion within 60 days of date of enrolment.
  • Ability and willingness of participant or legal guardian/representative to provide informed consent to participate in the home-based ACF (HACF) or telephonic ACF arm (TACF).

(NOTE: Illiterate participants or participants with cognitive disabilities may be enrolled based on local regulatory policies, with the appropriate provisions for informed consent.)

- All household contacts of TB cases who are able and willing to provide informed consent to participate are eligible. Household contacts who are <18 years old are eligible for enrolment if a legal guardian/representative provides informed consent.

Exclusion Criteria:

  • Completed anti-TB treatment at a private sector clinic or TU outside of the study (final visit not registered at one of the study TB units)
  • Actively on anti-TB treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Home-based Active Case Finding (HACF)
Other: Home-based Active Case Finding (HACF)
Existing healthcare workers at the participating NTEP TB units will visit all patient homes at 6 and 12 months post-treatment completion. They will administer a standardized TB symptom screen questionnaire to treated TB cases and their household contacts (HHC). All those who screen positive will have a spot sputum taken at the home for microbiological testing at the TB unit.
Active Comparator: Telephonic Active Case Finding (TACF)
Other: Telephonic Active Case Finding (TACF)
Existing healthcare workers at the participating NTEP TB Units will administer a standardized TB symptom screen questionnaire to the index patient via telephone calls at 6 and 12 months post-treatment completion. The index patient will also be asked about any TB symptoms among household contacts (HHCs). If TB is suspected among any HH members, a home visit will be conducted and spot sputum specimens will be collected for microbiological testing at the TB unit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate per 100 person-years of people diagnosed with new or recurrent TB by study arm.
Time Frame: Within 12 months following index TB patient's treatment completion date.
TB disease will be diagnosed as microbiologically confirmed (positive acid fast bacilli smear or positive Xpert® Mycobacterium tuberculosis/resistance to rifampin (MTB/RIF) assays or positive culture) or clinically diagnosed (initiated on TB treatment with no microbiological confirmation).
Within 12 months following index TB patient's treatment completion date.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of eligible household contacts (HHCs) <6 years of age, by study arm, initiated on TB preventive treatment (TPT) after ruling out active TB disease.
Time Frame: Up to 18 months following index TB patient's treatment completion date.
At enrolment, participants will report names of HHCs < 6 years of age and their history of TPT. Children who have not yet initiated TPT will be the denominator and children who initiate TPT following index patient enrolment will be the numerator.
Up to 18 months following index TB patient's treatment completion date.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
Dr. D.Y. Patil Medical College, Hospital and Research Centre

Investigators

  • Principal Investigator: Jonathan Golub, PhD, Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 29, 2021

Primary Completion (Estimated)

August 1, 2024

Study Completion (Estimated)

August 1, 2024

Study Registration Dates

First Submitted

April 1, 2020

First Submitted That Met QC Criteria

April 1, 2020

First Posted (Actual)

April 3, 2020

Study Record Updates

Last Update Posted (Actual)

August 16, 2023

Last Update Submitted That Met QC Criteria

August 14, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00247239
  • 1R01AI143748-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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