Factors associated with non-completion of follow-up: 33-month latent tuberculous infection treatment trial

Abstract

Setting: A post-hoc exploratory analysis of a randomized, open-label clinical trial that enrolled 8053 participants from the United States, Canada, Brazil, and Spain.

Objective: To assess factors associated with non-completion of study follow-up (NCF) in a 33-month latent tuberculous infection treatment trial, PREVENT TB.

Design: Participants were randomized to receive 3 months of weekly directly observed therapy vs. 9 months of daily self-administered therapy. NCF was defined as failing to be followed for at least 993 days (33 months) from enrollment. Possible factors associated with NCF were analyzed using univariate and multivariate regression via Cox proportional hazard model.

Results: Of 7061 adults selected for analysis, 841 (11.9%) did not complete study follow-up. Homelessness, young age, low education, history of incarceration, smoking, missing an early clinic visit, receiving isoniazid only, and male sex were significantly associated with NCF. Similar results were found in the North American region (United States and Canada) only. In Brazil and Spain, the only significant factor was missing an early clinic visit.

Conclusions: Study subjects at higher risk for NCF were identified by characteristics known at enrollment or in early follow-up. Evaluation of follow-up in other trials might help determine whether the identified factors consistently correlate with retention.

Trial registration: ClinicalTrials.gov NCT00023452.

Figure

Flow chart of participants evaluated for factors associated with non-completion of study follow-up in a 33-month Clinical Trial of Latent Tuberculosis Infection Treatment, the PREVENT TB Trial. This figure shows the number of participants who were enrolled in the trial, the groups that were excluded from the analysis, and the remaining cohort that was evaluated for factors associated with non-completion of study follow-up, by region. Inclusion criteria were as follows: 1) close contact with a culture-confirmed PTB patient (within 2 years before enrollment) and TST-positive; 2) recent conversion to TST positivity; 3) HIV infection plus TST-positive or recent close contact with a culture-confirmed PTB patient regardless of TST results; or 4) TST-positive with fibrotic changes on chest radiograph consistent with previously untreated TB. Exclusion criteria were as follows: 1) current confirmed TB; 2) suspected TB; 3) TB resistant to INH or RMP in the source case; 4) history of treatment for >14consecutive days with a rifamycin or >30 consecutive days with INH during the previous 2 years; 5) documented history of completing adequate treatment for active TB or latent M. tuberculosis infection in an HIV-negative person; 6) history of sensitivity/intolerance to INH or rifamycins, 7) serum AST >5 times the upper limit of normal if AST was determined, 8) pregnant or lactating females (not excluded in this cohort for analysis), 9) persons currently receiving or planning to receive HIV-1 therapy within 90 days of enrollment, or 10) weight <10.0 kg. PREVENT TB Trial reasons for ineligibility: source case INH/RMP-resistant (50%), source case culture-negative (31%), other (19%). This analysis includes participants from all enrolling sites: the United States, Canada, Brazil and Spain. * This analysis considers only adults aged ⩾ 18 years. ^†Microbiological and non-microbiological ineligibles. ^‡Participants who did not have the opportunity to complete at least 993 days of study follow-up due to closure of enrolling site; clustering below and above 900 days: 59.3% (16/27) were followed in the trial between 687 and 889 days and 40.7% (11/27) between 915 and 991 days. PTB = pulmonary tuberculosis; TST = tuberculosis skin test; HIV = human immunodeficiency virus; INH = isoniazid; RMP = rifompicin; AST = aspartate immunotransferase.