Background Treatment of rifampicin-resistant tuberculosis (RR-TB) involves drugs that can prolong the QT interval. There is limited data on risk factors and the level of cardiac monitoring required. We analysed STREAM Stage 2 data to address these issues.

Methods A post-hoc analysis was undertaken of data from participants allocated to 3 regimens: 9-month control (n=202), 9-month oral (n=211) and 6-month (n=143). Risk factors for development of a QT or QTcF interval ≥500ms were assessed. The diagnostic accuracy of a monitoring strategy for QT/QTcF prolongation was tested.

Results QT/QTcF ≥500ms occurred on all regimens: 9-month control (n=14 (6.9%)), 9-month oral (n=8 (3.8%)) and 6-month (n=6 (4.2%)).

The participating country with the highest number of QT/QTcF interval ≥500ms events was Mongolia (18 events [64%]). A higher baseline QTcF was significantly associated with development of QT/QTcF ≥500ms (OR 1.05; 95% CI 1.03 to 1.07, p<0.001). There was a suggested association between moxifloxacin (compared to levofloxacin, OR 2.49; 95% CI 0.92 to 6.71, p = 0.07) and a higher baseline TSH (OR 3.52; 95% CI 0.84 to 14.73, p=0.08) and increased odds of QT/QTcF ≥500ms.

The monitoring strategy performed well in the control (sensitivity 100%; specificity 62%; positive predictive value (PPV) 13% and negative predictive value (NPV) 100%) and oral (sensitivity 100%, specificity 59%, PPV 6% and NPV 100%) regimen groups.

Conclusions Baseline QTcF and country were associated with increased odds of QT/QTcF prolongation. The monitoring strategy performed well in the identification of participants at higher risk of QT/QTcF prolongation.

The authors have declared no competing interest.

NCT02409290

STREAM Stage 1 was funded by the US Agency for International Development (USAID) through the Cooperative Agreement GHN-A-00–08–0004–00. Stage 2 of STREAM was jointly funded by USAID and Janssen Research & Development. Additional funding for STREAM was provided by the Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC–DFID Concordat agreement, which is also part of the European and Developing Countries Clinical Trials Partnership-2 programme supported by the EU. The MRC Clinical Trials Unit at University College London was supported by the MRC (MC_UU_00004/04).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Union Ethics Advisory Group (EAG) approved (i) the use of deidentified data from the STREAM trials for this post-hoc secondary analysis, and (ii) the waiver of requirement for additional consent from participants (EAG 53/19).

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