drugset / Trial / NCT00760149
Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis
Phase 2
Completed
150 enrolled
Radboud University Medical Center
European and Developing Countries Clinical Trials Partnership (EDCTP) · collabKibong'oto National Tuberculosis Hospital, Sanya Juu, Tanzania · collabKilimanjaro Christian Medical Centre, Tanzania · collabNational Institute for Public Health and the Environment (RIVM) · collabSanofi · collabUniversity Centre for Chronic Diseases Dekkerswald, Groesbeek, The Netherlands · collab
RandomizedParallel-groupQuadruple-blindTreatment
Summary
In this phase II clinical trial, the pharmacokinetics, safety and (short-term) efficacy of higher than standard doses rifampicin will be studied during the intensive phase of tuberculosis (TB) treatment. Patients enrolled in this study will either get the standard TB regimen (including 600 mg rifampicin; first study arm), or 900 mg rifampicin plus isoniazid, ethambutol and pyrazinamide in standard dosages (second study arm), or 1200 mg rifampicin plus the other drugs in standard dosages (third study arm). All patients will get the standard TB regimen during the continuation phase of treatment.
Timeline
- Start
- 2010-07
- Primary completion
- 2013-09
- Completion
- 2013-09
Publications
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- Background Ginsberg AM, Spigelman M. Challenges in tuberculosis drug research and development. Nat Med. 2007 Mar;13(3):290-4. doi: 10.1038/nm0307-290. No abstract available.
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- Background Diacon AH, Patientia RF, Venter A, van Helden PD, Smith PJ, McIlleron H, Maritz JS, Donald PR. Early bactericidal activity of high-dose rifampin in patients with pulmonary tuberculosis evidenced by positive sputum smears. Antimicrob Agents Chemother. 2007 Aug;51(8):2994-6. doi: 10.1128/AAC.01474-06. Epub 2007 May 21.
- Background Jayaram R, Gaonkar S, Kaur P, Suresh BL, Mahesh BN, Jayashree R, Nandi V, Bharat S, Shandil RK, Kantharaj E, Balasubramanian V. Pharmacokinetics-pharmacodynamics of rifampin in an aerosol infection model of tuberculosis. Antimicrob Agents Chemother. 2003 Jul;47(7):2118-24. doi: 10.1128/AAC.47.7.2118-2124.2003.
- Background Kreis B, Pretet S, Birenbaum J, Guibout P, Hazeman JJ, Orin E, Perdrizet S, Weil J. Two three-month treatment regimens for pulmonary tuberculosis. Bull Int Union Tuberc. 1976;51(1):71-5. No abstract available.
- Background Long MW, Snider DE Jr, Farer LS. U.S. Public Health Service Cooperative trial of three rifampin-isoniazid regimens in treatment of pulmonary tuberculosis. Am Rev Respir Dis. 1979 Jun;119(6):879-94. doi: 10.1164/arrd.1979.119.6.879.
- Background Burman WJ, Gallicano K, Peloquin C. Comparative pharmacokinetics and pharmacodynamics of the rifamycin antibacterials. Clin Pharmacokinet. 2001;40(5):327-41. doi: 10.2165/00003088-200140050-00002.
- Background Ruslami R, Nijland HM, Alisjahbana B, Parwati I, van Crevel R, Aarnoutse RE. Pharmacokinetics and tolerability of a higher rifampin dose versus the standard dose in pulmonary tuberculosis patients. Antimicrob Agents Chemother. 2007 Jul;51(7):2546-51. doi: 10.1128/AAC.01550-06. Epub 2007 Apr 23.
- Background Ruslami R, Nijland H, Aarnoutse R, Alisjahbana B, Soeroto AY, Ewalds S, van Crevel R. Evaluation of high- versus standard-dose rifampin in Indonesian patients with pulmonary tuberculosis. Antimicrob Agents Chemother. 2006 Feb;50(2):822-3. doi: 10.1128/AAC.50.2.822-823.2006. No abstract available.
- Background Solera J, Rodriguez-Zapata M, Geijo P, Largo J, Paulino J, Saez L, Martinez-Alfaro E, Sanchez L, Sepulveda MA, Ruiz-Ribo MD. Doxycycline-rifampin versus doxycycline-streptomycin in treatment of human brucellosis due to Brucella melitensis. The GECMEI Group. Grupo de Estudio de Castilla-la Mancha de Enfermedades Infecciosas. Antimicrob Agents Chemother. 1995 Sep;39(9):2061-7. doi: 10.1128/AAC.39.9.2061.
- Background Kochar DK, Aseri S, Sharma BV, Bumb RA, Mehta RD, Purohit SK. The role of rifampicin in the management of cutaneous leishmaniasis. QJM. 2000 Nov;93(11):733-7. doi: 10.1093/qjmed/93.11.733.
- Background Rosenthal IM, Williams K, Tyagi S, Peloquin CA, Vernon AA, Bishai WR, Grosset JH, Nuermberger EL. Potent twice-weekly rifapentine-containing regimens in murine tuberculosis. Am J Respir Crit Care Med. 2006 Jul 1;174(1):94-101. doi: 10.1164/rccm.200602-280OC. Epub 2006 Mar 30.
- Background Fox W, Ellard GA, Mitchison DA. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications. Int J Tuberc Lung Dis. 1999 Oct;3(10 Suppl 2):S231-79. No abstract available.
- Background Peloquin CA, Namdar R, Singleton MD, Nix DE. Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids. Chest. 1999 Jan;115(1):12-8. doi: 10.1378/chest.115.1.12.
- Background Tappero JW, Bradford WZ, Agerton TB, Hopewell P, Reingold AL, Lockman S, Oyewo A, Talbot EA, Kenyon TA, Moeti TL, Moffat HJ, Peloquin CA. Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana. Clin Infect Dis. 2005 Aug 15;41(4):461-9. doi: 10.1086/431984. Epub 2005 Jul 8.
- Background Grosset J, Leventis S. Adverse effects of rifampin. Rev Infect Dis. 1983 Jul-Aug;5 Suppl 3:S440-50. doi: 10.1093/clinids/5.supplement_3.s440.
- Background Brindle R, Odhiambo J, Mitchison D. Serial counts of Mycobacterium tuberculosis in sputum as surrogate markers of the sterilising activity of rifampicin and pyrazinamide in treating pulmonary tuberculosis. BMC Pulm Med. 2001;1:2. doi: 10.1186/1471-2466-1-2.
- Background Mitchison DA. Assessment of new sterilizing drugs for treating pulmonary tuberculosis by culture at 2 months. Am Rev Respir Dis. 1993 Apr;147(4):1062-3. doi: 10.1164/ajrccm/147.4.1062. No abstract available.
- Background Mitchison DA. Modern methods for assessing the drugs used in the chemotherapy of mycobacterial disease. Soc Appl Bacteriol Symp Ser. 1996;25:72S-80S. No abstract available.
- Background Jindani A, Aber VR, Edwards EA, Mitchison DA. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Rev Respir Dis. 1980 Jun;121(6):939-49. doi: 10.1164/arrd.1980.121.6.939. No abstract available.
- Background Wallis RS, Perkins MD, Phillips M, Joloba M, Namale A, Johnson JL, Whalen CC, Teixeira L, Demchuk B, Dietze R, Mugerwa RD, Eisenach K, Ellner JJ. Predicting the outcome of therapy for pulmonary tuberculosis. Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 1):1076-80. doi: 10.1164/ajrccm.161.4.9903087.
- Background Burman WJ. The hunt for the elusive surrogate marker of sterilizing activity in tuberculosis treatment. Am J Respir Crit Care Med. 2003 May 15;167(10):1299-301. doi: 10.1164/rccm.2302003. No abstract available.
- Background Jindani A, Dore CJ, Mitchison DA. Bactericidal and sterilizing activities of antituberculosis drugs during the first 14 days. Am J Respir Crit Care Med. 2003 May 15;167(10):1348-54. doi: 10.1164/rccm.200210-1125OC. Epub 2003 Jan 6.
- Background Sirgel FA, Fourie PB, Donald PR, Padayatchi N, Rustomjee R, Levin J, Roscigno G, Norman J, McIlleron H, Mitchison DA. The early bactericidal activities of rifampin and rifapentine in pulmonary tuberculosis. Am J Respir Crit Care Med. 2005 Jul 1;172(1):128-35. doi: 10.1164/rccm.200411-1557OC. Epub 2005 Apr 1.
- Background Hafner R, Cohn JA, Wright DJ, Dunlap NE, Egorin MJ, Enama ME, Muth K, Peloquin CA, Mor N, Heifets LB. Early bactericidal activity of isoniazid in pulmonary tuberculosis. Optimization of methodology. The DATRI 008 Study Group. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):918-23. doi: 10.1164/ajrccm.156.3.9612016.
- Background Desjardin LE, Perkins MD, Wolski K, Haun S, Teixeira L, Chen Y, Johnson JL, Ellner JJ, Dietze R, Bates J, Cave MD, Eisenach KD. Measurement of sputum Mycobacterium tuberculosis messenger RNA as a surrogate for response to chemotherapy. Am J Respir Crit Care Med. 1999 Jul;160(1):203-10. doi: 10.1164/ajrccm.160.1.9811006.
- Background Peloquin CA. Pharmacological issues in the treatment of tuberculosis. Ann N Y Acad Sci. 2001 Dec;953:157-64. doi: 10.1111/j.1749-6632.2001.tb11374.x.
- Background Ribeiro-Rodrigues R, Resende Co T, Johnson JL, Ribeiro F, Palaci M, Sa RT, Maciel EL, Pereira Lima FE, Dettoni V, Toossi Z, Boom WH, Dietze R, Ellner JJ, Hirsch CS. Sputum cytokine levels in patients with pulmonary tuberculosis as early markers of mycobacterial clearance. Clin Diagn Lab Immunol. 2002 Jul;9(4):818-23. doi: 10.1128/cdli.9.4.818-823.2002.
- Background Quaedvlieg V, Henket M, Sele J, Louis R. Cytokine production from sputum cells in eosinophilic versus non-eosinophilic asthmatics. Clin Exp Immunol. 2006 Jan;143(1):161-6. doi: 10.1111/j.1365-2249.2005.02968.x.
- Background Colombo C, Costantini D, Rocchi A, Cariani L, Garlaschi ML, Tirelli S, Calori G, Copreni E, Conese M. Cytokine levels in sputum of cystic fibrosis patients before and after antibiotic therapy. Pediatr Pulmonol. 2005 Jul;40(1):15-21. doi: 10.1002/ppul.20237.
- Background Husson MO, Wizla-Derambure N, Turck D, Gosset P, Wallaert B. Effect of intermittent inhaled tobramycin on sputum cytokine profiles in cystic fibrosis. J Antimicrob Chemother. 2005 Jul;56(1):247-9. doi: 10.1093/jac/dki179. Epub 2005 Jun 2.
- Background Casarini M, Ameglio F, Alemanno L, Zangrilli P, Mattia P, Paone G, Bisetti A, Giosue S. Cytokine levels correlate with a radiologic score in active pulmonary tuberculosis. Am J Respir Crit Care Med. 1999 Jan;159(1):143-8. doi: 10.1164/ajrccm.159.1.9803066.
- Background Verver S, Warren RM, Beyers N, Richardson M, van der Spuy GD, Borgdorff MW, Enarson DA, Behr MA, van Helden PD. Rate of reinfection tuberculosis after successful treatment is higher than rate of new tuberculosis. Am J Respir Crit Care Med. 2005 Jun 15;171(12):1430-5. doi: 10.1164/rccm.200409-1200OC. Epub 2005 Apr 14.
- Background van Rie A, Victor TC, Richardson M, Johnson R, van der Spuy GD, Murray EJ, Beyers N, Gey van Pittius NC, van Helden PD, Warren RM. Reinfection and mixed infection cause changing Mycobacterium tuberculosis drug-resistance patterns. Am J Respir Crit Care Med. 2005 Sep 1;172(5):636-42. doi: 10.1164/rccm.200503-449OC. Epub 2005 Jun 9.
- Background Kibiki GS, Mulder B, Dolmans WM, de Beer JL, Boeree M, Sam N, van Soolingen D, Sola C, van der Zanden AG. M. tuberculosis genotypic diversity and drug susceptibility pattern in HIV-infected and non-HIV-infected patients in northern Tanzania. BMC Microbiol. 2007 May 31;7:51. doi: 10.1186/1471-2180-7-51.
- Aarnoutse RE, Kibiki GS, Reither K, Semvua HH, Haraka F, Mtabho CM, Mpagama SG, van den Boogaard J, Sumari-de Boer IM, Magis-Escurra C, Wattenberg M, Logger JGM, Te Brake LHM, Hoelscher M, Gillespie SH, Colbers A, Phillips PPJ, Plemper van Balen G, Boeree MJ; PanACEA Consortium. Pharmacokinetics, Tolerability, and Bacteriological Response of Rifampin Administered at 600, 900, and 1,200 Milligrams Daily in Patients with Pulmonary Tuberculosis. Antimicrob Agents Chemother. 2017 Oct 24;61(11):e01054-17. doi: 10.1128/AAC.01054-17. Print 2017 Nov.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Rifampin | Small molecule | 900 mg | Oral |
| Comparator | Rifampin | Small molecule | 1200 mg | Oral |