High-dose rifapentine with moxifloxacin for pulmonary tuberculosis
Amina Jindani, Thomas S Harrison, Andrew J Nunn, Patrick P J Phillips, Gavin J Churchyard, Salome Charalambous, Mark Hatherill, Hennie Geldenhuys, Helen M McIlleron, Simbarashe P Zvada, Stanley Mungofa, Nasir A Shah, Simukai Zizhou, Lloyd Magweta, James Shepherd, Sambayawo Nyirenda, Janneke H van Dijk, Heather E Clouting, David Coleman, Anna L E Bateson, Timothy D McHugh, Philip D Butcher, Denny A Mitchison, RIFAQUIN Trial Team, Amina Jindani, Denny Mitchison, Tom Harrison, David Coleman, Philip Butcher, Andrew Nunn, Patrick Phillips, Heather Clouting, Lyndsey Castle, Margaret Thomason, Michelle Tetlow, Claire Mulrenan, Bethany James, Ellen Owen-Powell, Claire Cook, Sue Tebbs, Karen Sanders, Nadine Van-Looy, Victoria Yorke-Edwards, Hannah Bundy, Angela Crook, Mark Hatherill, Hennie Geldehuys, Danelle van As, Susan Rossouw, Willem Hanekom, Andrew Whitelaw, Helen McIlleron, Simbarashe Zvada, Lubbe Wiesner, Sandra Meredith, Gavin Churchyard, Salome Charalambous, Sello Mashamaite, Nicolene Gardiner, Nicolaas Pool, Janneke van Dijk, Francis Hamangaba, Stanley Mungofa, Nasir Syed, Molly Mubungani, Kelvin Chifeya, Dadirai Mungoma, Ronnie Matambo, Jesca Mhaka, Beauty Makamure, Simukai Zizhou, Temba Ncomanzi, Lloyd Magweta, Virginia Taderera, Newten Muzungu, James Shepherd, Samba Nyirenda, Joyce Basotli, Unami Mathebula, Taraz Samandari, Tefera Agizew, Tedla Zegabriel, Felicity Masunge, Evelyn Dintwa, Chipo Mogorosi, Balladiah Chingapane, Kuda Mpatane, Motlelepula Letsholathebe, Sebongile Monyi, Mmapula Malibala, Ogolotse Tshiamo, Kefenste Tumedi, Mirriam Montshiwa, Onani Zimba, Kunle Dare, Ritah Moathodi, Tim McHugh, Anna Bateson, Amina Jindani, Thomas S Harrison, Andrew J Nunn, Patrick P J Phillips, Gavin J Churchyard, Salome Charalambous, Mark Hatherill, Hennie Geldenhuys, Helen M McIlleron, Simbarashe P Zvada, Stanley Mungofa, Nasir A Shah, Simukai Zizhou, Lloyd Magweta, James Shepherd, Sambayawo Nyirenda, Janneke H van Dijk, Heather E Clouting, David Coleman, Anna L E Bateson, Timothy D McHugh, Philip D Butcher, Denny A Mitchison, RIFAQUIN Trial Team, Amina Jindani, Denny Mitchison, Tom Harrison, David Coleman, Philip Butcher, Andrew Nunn, Patrick Phillips, Heather Clouting, Lyndsey Castle, Margaret Thomason, Michelle Tetlow, Claire Mulrenan, Bethany James, Ellen Owen-Powell, Claire Cook, Sue Tebbs, Karen Sanders, Nadine Van-Looy, Victoria Yorke-Edwards, Hannah Bundy, Angela Crook, Mark Hatherill, Hennie Geldehuys, Danelle van As, Susan Rossouw, Willem Hanekom, Andrew Whitelaw, Helen McIlleron, Simbarashe Zvada, Lubbe Wiesner, Sandra Meredith, Gavin Churchyard, Salome Charalambous, Sello Mashamaite, Nicolene Gardiner, Nicolaas Pool, Janneke van Dijk, Francis Hamangaba, Stanley Mungofa, Nasir Syed, Molly Mubungani, Kelvin Chifeya, Dadirai Mungoma, Ronnie Matambo, Jesca Mhaka, Beauty Makamure, Simukai Zizhou, Temba Ncomanzi, Lloyd Magweta, Virginia Taderera, Newten Muzungu, James Shepherd, Samba Nyirenda, Joyce Basotli, Unami Mathebula, Taraz Samandari, Tefera Agizew, Tedla Zegabriel, Felicity Masunge, Evelyn Dintwa, Chipo Mogorosi, Balladiah Chingapane, Kuda Mpatane, Motlelepula Letsholathebe, Sebongile Monyi, Mmapula Malibala, Ogolotse Tshiamo, Kefenste Tumedi, Mirriam Montshiwa, Onani Zimba, Kunle Dare, Ritah Moathodi, Tim McHugh, Anna Bateson
Abstract
Background: Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed.
Methods: We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals.
Results: We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, -1.8 percentage points; 90% confidence interval [CI], -6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, -4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4).
Conclusions: The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen. The 4-month regimen was not noninferior to the control regimen. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; RIFAQUIN Current Controlled Trials number, ISRCTN44153044.).
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Source: PubMed