Tuberculosis (TB) Aftermath: study protocol for 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

Authors

Samyra R. Cox, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD, 21205, USA. scox26@jh.edu.
Abhay Kadam, Johns Hopkins India, G-4 & G-5, PHOENIX Building, OPP. to Residency Club, Pune, Maharashtra, 411001, India.
Sachin Atre, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Sant Tukaram Nagar, Pimpri Colony, Pimpri-Chinchwad, Maharashtra, 411018, India.
Akshay N. Gupte, Johns Hopkins School of Medicine, 600 N Wolfe St, Baltimore, MD, 21287, USA.
Hojoon Sohn, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD, 21205, USA.
Nikhil Gupte, Johns Hopkins School of Medicine, 600 N Wolfe St, Baltimore, MD, 21287, USA.
Trupti Sawant, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Sant Tukaram Nagar, Pimpri Colony, Pimpri-Chinchwad, Maharashtra, 411018, India.
Vishal Mhadeshwar, Johns Hopkins India, G-4 & G-5, PHOENIX Building, OPP. to Residency Club, Pune, Maharashtra, 411001, India.
Ryan Thompson, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD, 21205, USA.
Emily Kendall, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD, 21205, USA.
Christopher Hoffmann, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD, 21205, USA.
Nishi Suryavanshi, Johns Hopkins School of Medicine, 600 N Wolfe St, Baltimore, MD, 21287, USA.
Deanna Kerrigan, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD, 21205, USA.
Srikanth Tripathy, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Sant Tukaram Nagar, Pimpri Colony, Pimpri-Chinchwad, Maharashtra, 411018, India.
Arjunlal Kakrani, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Sant Tukaram Nagar, Pimpri Colony, Pimpri-Chinchwad, Maharashtra, 411018, India.
Madhusudan S. Barthwal, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Sant Tukaram Nagar, Pimpri Colony, Pimpri-Chinchwad, Maharashtra, 411018, India.
Vidya Mave, Johns Hopkins School of Medicine, 600 N Wolfe St, Baltimore, MD, 21287, USA.
Jonathan E. Golub, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD, 21205, USA.

Document Type

Journal Article

Publication Date

8-5-2022

Journal

Trials

Volume

23

Issue

1

DOI

10.1186/s13063-022-06503-6

Keywords

Active case finding; Hybrid effectiveness-implementation trial; India; Recurrence; Tuberculosis

Abstract

BACKGROUND: 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. We 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 their household contacts (HHCs). METHODS: We will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their 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. We 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. DISCUSSION: 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. TRIAL REGISTRATION: NCT04333485 , registered April 3, 2020. CTRI/2020/05/025059 [Clinical Trials Registry of India], registered May 6 2020.

Department

Prevention and Community Health

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