Impact on Patients’ Treatment Outcomes of XpertMTB/RIF Implementation for the Diagnosis of Tuberculosis: Follow-Up of a Stepped-Wedge Randomized Clinical Trial

Abstract

IntroductionThe impact on treatment outcomes of XpertMTB/RIF, a molecular-based test that provides rapid diagnosis of tuberculosis (TB) and rifampicin resistance with high accuracy, has not been reported despite its adoption in a few countries. We here report treatment outcomes in a step-wedged cluster randomized trial for patients diagnosed with XpertMTB/RIF compared to patients diagnosed with sputum smear examination in public health facilities in Brazil.MethodsTreatment outcome data were added to the trial database of patients diagnosed from 4 February to 4 October 2012, and crosschecked with data from the national mortality and the drug-resistant TB registers. Treatment outcomes in the intervention (n=2232) and baseline (n=1856) arms were compared using a multilevel regression model.ResultsUnfavourable outcomes were frequent in both arms, mainly due to loss to follow-up (16%). Overall unfavourable outcomes were not reduced in the intervention arm (29.6% versus 31.7%, OR=0.93; 95%CI=0.79-1.08). However, the overall TB-attributed death rate was lower in the intervention arm (2.3% vs. 3.8%). Adjusted for HIV status, age group and city, the intervention resulted in a 35% decrease in TB-attributed deaths (OR=0.65, 95%CI=0.44-0.97).ConclusionsThe proportion of patients successfully treated did not increase with Xpert MTB/RIF implementation, with high loss to follow-up rates in both arms. We did observe a 35% reduction in TB-related mortality, which we hypothesize may be explained by less advanced disease among the smear-negative patients diagnosed by Xpert. In conclusion, XpertMTB/RIF introduction did not improve TB treatment outcomes in Brazil.Trial Registrationclinicaltrials.gov NCT01363765

Novel methods for the analysis of stepped wedge cluster randomized trials

“…We applied the methods discussed here to a SW‐CRT that assessed the effect of a TB diagnostic test on reducing unsuccessful (noncure) outcomes of adults on TB treatment . Note that this is the same trial reanalyzed by Thompson et al using the within‐period methods they proposed.…”

Unsuccessful Xpert® MTB/RIF results: the Nigerian experience

“…The patient population screened, which comprised presumptive drug-resistant cases and patients with human immunodeficiency virus with TB symptoms, contributed to the high RR-TB detection rate. The main impetus was the timely detection of multidrug-resistant TB, [16][17][18][19] as RMP resistance is a surrogate for isoniazid resistance. 20,21 The key lesson learnt from the Xpert roll-out was that access to diagnosis is not the only indicator for measuring successful implementation; the rate of unsuccessful tests (which add no value to treatment) is also an important indicator of the effectiveness of Xpert implementation over time.…”

Impacto orçamentário da incorporação do GeneXpert MTB/RIF para o diagnóstico da tuberculose pulmonar na perspectiva do Sistema Único de Saúde, Brasil, 2013-2017

“…Dados de acurácia do novo teste demonstraram uma sensibilidade de 89% (IC95%: 85%; 92%) e especificidade de 99% (IC95%: 98%; 99%) em substituição à baciloscopia de primeira amostra 7 para a detecção de TB. Material insuficiente (escarro) ou inadequado (presença de saliva) são problemas observados durante a sua realização 18,19 .…”