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Model-Predicted Imp...
Model-Predicted Impact of ECG Monitoring Strategies During Bedaquiline Treatment
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- van Beek, Stijn W. (författare)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Geert Grootepl Zuid 10, NL-6525 GA Nijmegen, Netherlands.
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- Tanneau, Lénaïg (författare)
- Uppsala universitet,Institutionen för farmaci
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- Meintjes, Graeme (författare)
- Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Inst Infect Dis & Mol Med, Dept Med, Cape Town, South Africa.
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- Wasserman, Sean (författare)
- Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Inst Infect Dis & Mol Med, Dept Med, Cape Town, South Africa.;Univ Cape Town, Dept Med, Div Infect Dis & HIV Med, Cape Town, South Africa.
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- Gandhi, Neel R. (författare)
- Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.;Emory Univ, Dept Global Hlth, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.;Emory Univ, Dept Med, Emory Sch Med, Div Infect Dis, Atlanta, GA 30322 USA.
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- Campbell, Angie (författare)
- Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.;Emory Univ, Dept Global Hlth, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
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- Viljoen, Charle A. (författare)
- Univ Cape Town, Dept Med, Div Cardiol, Cape Town, South Africa.;Univ Cape Town, Fac Hlth Sci, Cape Heart Inst, Cape Town, South Africa.
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- Wiesner, Lubbe (författare)
- Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa.
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- Aarnoutse, Rob E. (författare)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Geert Grootepl Zuid 10, NL-6525 GA Nijmegen, Netherlands.
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- Maartens, Gary (författare)
- Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Inst Infect Dis & Mol Med, Dept Med, Cape Town, South Africa.;Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa.
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- Brust, James C. M. (författare)
- Albert Einstein Coll Med, Div Gen Internal Med, Dept Med, Bronx, NY 10467 USA.
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- Svensson, Elin, 1985- (författare)
- Uppsala universitet,Institutionen för farmaci,Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Geert Grootepl Zuid 10, NL-6525 GA Nijmegen, Netherlands.
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Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Geert Grootepl Zuid 10, NL-6525 GA Nijmegen, Netherlands Institutionen för farmaci (creator_code:org_t)
- 2022-07-27
- 2022
- Engelska.
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Ingår i: OPEN FORUM INFECTIOUS DISEASES. - : Oxford University Press. - 2328-8957. ; 9:8
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Abstract
Ämnesord
Stäng
- Background: The M2 metabolite of bedaquiline causes QT-interval prolongation, making electrocardiogram (ECG) monitoring of patients receiving bedaquiline for drug-resistant tuberculosis necessary. The objective of this study was to determine the relationship between M2 exposure and Fridericia-corrected QT (QTcF)-interval prolongation and to explore suitable ECG monitoring strategies for 6-month bedaquiline treatment.Methods: Data from the PROBeX study, a prospective observational cohort study, were used to characterize the relationship between M2 exposure and QTcF. Established nonlinear mixed-effects models were fitted to pharmacokinetic and ECG data. In a virtual patient population, QTcF values were simulated for scenarios with and without concomitant clofazimine. ECG monitoring strategies to identify patients who need to interrupt treatment (QTcF > 500 ms) were explored.Results: One hundred seventy patients were included, providing 1131 bedaquiline/M2 plasma concentrations and 1702 QTcF measurements; 2.1% of virtual patients receiving concomitant clofazimine had QTcF > 500 ms at any point during treatment (0.7% without concomitant clofazimine). With monthly monitoring, almost all patients with QTcF > 500 ms were identified by week 12; after week 12, patients were predominantly falsely identified as QTcF > 500 ms due to stochastic measurement error. Following a strategy with monitoring before treatment and at weeks 2, 4, 8, and 12 in simulations with concomitant clofazimine, 93.8% of all patients who should interrupt treatment were identified, and 26.4% of all interruptions were unnecessary (92.1% and 32.2%, respectively, without concomitant clofazimine).Conclusions: Our simulations enable an informed decision for a suitable ECG monitoring strategy by weighing the risk of missing patients with QTcF > 500 ms and that of interrupting bedaquiline treatment unnecessarily. We propose ECG monitoring before treatment and at weeks 2, 4, 8, and 12 after starting bedaquiline treatment.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- bedaquiline
- QT-interval prolongation
- tuberculosis
- modeling
- ECG monitoring
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van Beek, Stijn ...
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Tanneau, Lénaïg
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Meintjes, Graeme
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Wasserman, Sean
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Gandhi, Neel R.
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Campbell, Angie
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visa fler...
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Viljoen, Charle ...
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Wiesner, Lubbe
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Aarnoutse, Rob E ...
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Maartens, Gary
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Brust, James C. ...
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Svensson, Elin, ...
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