Author:
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-
1.
World Health Organization, 2010. Guidelines for the Treatment of Malaria. Second edition. Available at: http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf. Accessed January 20, 2011.
-
2.
Premji ZG, 2009. Coartem: the journey to the clinic. Malar J 8 (Suppl 1): S3.
-
3.
Brewer TG, Peggins JO, Grate SJ, Petras JM, Levine BS, Weina PJ, Swearengen J, Heiffer MH, Schuster BG, 1994. Neurotoxicity in animals due to arteether and artemether. Trans R Soc Trop Med Hyg 88 (Suppl 1): S33–S36.
-
4.
Brewer TG, Grate SJ, Peggins JO, Weina PJ, Petras JM, Levine BS, Heiffer MH, Schuster BG, 1994. Fatal neurotoxicity of arteether and artemether. Am J Trop Med Hyg 51: 251–259.
-
5.
Petras JM, Kyle DE, Gettayacamin M, Young GD, Bauman RA, Webster HK, Corcoran KD, Peggins JO, Vane MA, Brewer TG, 1997. Arteether: risks of two-week administration in Macaca mulatta. Am J Trop Med Hyg 56: 390–396.
-
6.
Ribeiro IR, Olliaro P, 1998. Safety of artemisinin and its derivatives. A review of published and unpublished clinical trials. Med Trop 58 (Suppl 3): 50–53.
-
7.
Kissinger E, Hien TT, Hung NT, Nam ND, Tuyen NL, Dinh BV, Mann C, Phu NH, Loc PP, Simpson JA, White NJ, Farrar JJ, 2000. Clinical and neurophysiological study of the effects of multiple doses of artemisinin on brain-stem function in Vietnamese patients. Am J Trop Med Hyg 63: 48–55.
-
8.
Hien TT, Turner GD, Mai NT, Phu NH, Bethell D, Blakemore WF, Cavanagh JB, Dayan A, Medana I, Weller RO, Day NP, White NJ, 2003. Neuropathological assessment of artemether-treated severe malaria. Lancet 362: 295–296.
-
9.
Toovey S, Jamieson A, 2004. Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether. Trans R Soc Trop Med Hyg 98: 261–267.
-
10.
World Health Organization, 2000. Management of Severe Malaria: A Practical Handbook. Second edition. Available at: http://www.rollbackmalaria.org/docs/hbsm.pdf. Accessed January 20, 2011.
-
11.
World Health Organization, 2003. Assessment and Monitoring of Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria. Available at: http://whqlibdoc.who.int/hq/2003/WHO_HTM_RBM_2003.50.pdf. Accessed January 20, 2011.
-
12.
Felger I, Beck HP, 2002. Genotyping of Plasmodium falciparum: PCR-RFLP analysis. Doolan D, ed. Malaria Methods and Protocols: Methods in Molecular Medicine. Totawa, NJ: Humana Press, 117–129.
-
13.
Carhart R, Jerger J, 1959. Preferred method for clinical determination of pure-tone thresholds. J Speech Hear Disord 24: 330–345.
-
14.
Souppart C, Gauducheau N, Sandrenan N, Richard F, 2002. Development and validation of a high-performance liquid chromatography-mass spectrometry assay for the determination of artemether and its metabolite dihydroartemisinin in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 774: 195–203.
-
15.
Bergqvist Y, Hellgren U, Churchill FC, 1988. High-performance liquid chromatographic assay for the simultaneous monitoring of mefloquine and its acid metabolite in biological samples using protein precipitation and ion-pair extraction. J Chromatogr A 432: 252–263.
-
16.
Burkard RF, Don M, Eggermont JJ, 2007. Auditory Evoked Potentials: Basic Principles and Clinical Applications. Philadelphia, PA: Lippincott, Williams & Wilkins.
-
17.
Fausti SA, Flick CL, Bobal AM, Ellingson RM, Henry JA, Mitchell CR, 2003. Comparison of ABR stimuli for the early detection of ototoxicity: conventional clicks compared with high frequency clicks and single frequency tone bursts. J Am Acad Audiol 14: 239–250.
-
18.
Don M, Kwong B, 2002. Auditory brainstem response: differential diagnosis. Katz J, ed. Handbook of Clinical Audiology. Fifth edition. New York: Lippincott Williams & Wilkins, 274–297.
-
19.
Hecox K, Galambos R, 1974. Brain stem auditory evoked responses in human infants and adults. Arch Otolaryngol 99: 30–33.
-
20.
Clemis JD, Mc Gee T, 1979. Brain stem electric response audiometry in the differential diagnosis of acoustic tumors. Laryngoscope 89: 31–42.
-
21.
Bergholtz L, 1981. Normative data in clinical ABR. Scand Audiol Suppl 13: 75–81.
-
22.
Carrara VI, Phyo AP, Nwee P, Soe M, Htoo H, Arunkamomkiri J, Singhasivanon P, Nosten F, 2008. Auditory assessment of patients with acute uncomplicated Plasmodium falciparum malaria treated with three-day mefloquine-artesunate on the north-western border of Thailand. Malar J 7: 233.
-
23.
American Academy of Otolaryngology-Head and Neck Surgery Foundation, 1995. Committee on Hearing and Equilibrium guidelines for the evaluation of hearing preservation in acoustic neuroma (vestibular schwannoma). Otolaryngo Head Neck Surg 113: 179–180.
-
24.
Van Vugt M, Angus BJ, Price RN, Mann C, Simpson JA, Poletto C, Htoo SE, Looareesuwan S, White NJ, Nosten F, 2000. A case-control auditory evaluation of patients treated with artemisinin derivatives for multidrug-resistant Plasmodium falciparum malaria. Am J Trop Med Hyg 62: 65–69.
-
25.
Hutagalung R, Htoo H, Nwee P, Arunkamomkiri J, Zwang J, Carrara VI, Ashley E, Singhasivanon P, White NJ, Nosten F, 2006. A case-control auditory evaluation of patients treated with artemether-lumefantrine. Am J Trop Med Hyg 74: 211–214.
-
26.
McCall MB, Beynon AJ, Mylanus EA, van der Ven AJ, Sauerwein RW, 2006. No hearing loss associated with the use of artemether-lumefantrine to treat experimental human malaria. Trans R Soc Trop Med Hyg 100: 1098–1104.
-
27.
Gürkov R, Eshetu T, Miranda IB, Berens-Riha N, Mamo Y, Girma T, Krause E, Schmidt M, Hempel JM, Löscher T, 2008. Ototoxicity of artemether/lumefantrine in the treatment of falciparum malaria: a randomized trial. Malar J 7: 179.
-
28.
Mueller EA, van Vugt M, Kirch W, Andriano K, Hunt P, de Palacios PI, 2006. Efficacy and safety of the six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in adolescents and adults: a pooled analysis of individual patient data from randomized clinical trials. Acta Trop 100: 41–53.
-
29.
Mayxay M, Khanthavong M, Lindegårdh N, Keola S, Barends M, Pongvongsa T, Yapom R, Annerberg A, Phompida S, Phetsouvanh R, White NJ, Newton PN, 2004. Randomized comparison of chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in the Lao People's Democratic Republic. Clin Infect Dis 39: 1139–1147.
-
30.
Hutagalung R, Paiphun L, Ashley EA, McGready R, Brockman A, Thwai KL, Singhasivanon P, Jelinek T, White NJ, Nosten FH, 2005. A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand. Malar J 4: 46.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 22 | 22 | 6 |
| Full Text Views | 356 | 94 | 0 |
| PDF Downloads | 80 | 21 | 0 |
Randomized, Prospective, Three-Arm Study to Confirm the Auditory Safety and Efficacy of Artemether-Lumefantrine in Colombian Patients with Uncomplicated Plasmodium falciparum Malaria
Gabriel Carrasquilla
Gabriel Carrasquilla
Fundación Santa Fe de Bogotá, Bogotá, Colombia; Wayne State University, Detroit, Michigan; Novartis Pharma AG, Basel, Switzerland; House Ear Institute (HEI), Los Angeles, California
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Clemencia Barón
Clemencia Barón
Fundación Santa Fe de Bogotá, Bogotá, Colombia; Wayne State University, Detroit, Michigan; Novartis Pharma AG, Basel, Switzerland; House Ear Institute (HEI), Los Angeles, California
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Edwin M. Monsell
Edwin M. Monsell
Fundación Santa Fe de Bogotá, Bogotá, Colombia; Wayne State University, Detroit, Michigan; Novartis Pharma AG, Basel, Switzerland; House Ear Institute (HEI), Los Angeles, California
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Marc Cousin
Marc Cousin
Fundación Santa Fe de Bogotá, Bogotá, Colombia; Wayne State University, Detroit, Michigan; Novartis Pharma AG, Basel, Switzerland; House Ear Institute (HEI), Los Angeles, California
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Verena Walter
Verena Walter
Fundación Santa Fe de Bogotá, Bogotá, Colombia; Wayne State University, Detroit, Michigan; Novartis Pharma AG, Basel, Switzerland; House Ear Institute (HEI), Los Angeles, California
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Gilbert Lefèvre
Gilbert Lefèvre
Fundación Santa Fe de Bogotá, Bogotá, Colombia; Wayne State University, Detroit, Michigan; Novartis Pharma AG, Basel, Switzerland; House Ear Institute (HEI), Los Angeles, California
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Oliver Sander
Oliver Sander
Fundación Santa Fe de Bogotá, Bogotá, Colombia; Wayne State University, Detroit, Michigan; Novartis Pharma AG, Basel, Switzerland; House Ear Institute (HEI), Los Angeles, California
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Laurel M. Fisher
Laurel M. Fisher
Fundación Santa Fe de Bogotá, Bogotá, Colombia; Wayne State University, Detroit, Michigan; Novartis Pharma AG, Basel, Switzerland; House Ear Institute (HEI), Los Angeles, California
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The safety of artemether-lumefantrine in patients with acute, uncomplicated Plasmodium falciparum malaria was investigated prospectively using the auditory brainstem response (ABR) and pure-tone thresholds. Secondary outcomes included polymerase chain reaction-corrected cure rates. Patients were randomly assigned in a 3:1:1 ratio to either artemether-lumefantrine (N = 159), atovaquone-proguanil (N = 53), or artesunate-mefloquine (N = 53). The null hypothesis (primary outcome), claiming that the percentage of patients with a baseline to Day-7 ABR Wave III latency increase of > 0.30 msec is ≥ 15% after administration of artemether-lumefantrine, was rejected; 2.6% of patients (95% confidence interval: 0.7–6.6) exceeded 0.30 msec, i.e., significantly below 15% (P < 0.0001). A model-based analysis found no apparent relationship between drug exposure and ABR change. In all three groups, average improvements (2–4 dB) in pure-tone thresholds were observed, and polymerase chain reaction-corrected cure rates were > 95% to Day 42. The results support the continued safe and efficacious use of artemether-lumefantrine in uncomplicated falciparum malaria.
Author Notes
Financial support: This study was supported by Novartis Pharma Ltd., Basel, Switzerland.
Disclosure: Marc Cousin, Verena Walter, Gilbert Lefèvre, and Oliver Sander are employees of Novartis Pharma Ltd.
Authors' addresses: Gabriel Carrasquilla and Clemencia Barón, Centro de Estudios e Investigación en Salud-CEIS, Fundación Santa Fe de Bogotá, Bogotá, DC, Colombia, E-mails: Gabriel.Carrasquilla@fsfb.org.co and cbaron@cable.net.co. Edwin M. Monsell, Department of Otolaryngology-Head and Neck Surgery, Wayne State University, Detroit, MI, E-mail: emonsell@med.wayne.edu. Marc Cousin, Established Medicines DF/Tropical Medicines, Novartis Pharma AG, Basel, Switzerland, E-mail: marc.cousin@novartis.com. Verena Walter, Integrated Information Sciences, Novartis Pharma AG, Basel, Switzerland, E-mail: verena.walter@novartis.com. Gilbert Lefèvre, Translational Sciences, Novartis Pharma AG, Basel, Switzerland, E-mail: gilbert.lefevre@novartis.com. Oliver Sander, Modeling and Simulation, CHBS, Novartis Pharma AG, Basel, Switzerland, E-mail: oliver.sander@novartis.com. Laurel M. Fisher, House Ear Institute (HEI), Los Angeles, CA, E-mail: lfisher@hei.org.
Reprint requests: Gabriel Carrasquilla, Centro de Estudios e Investigación en Salud-CEIS, Fundación Santa Fe de Bogotá, Carrera 7B No. 123-90, Bogotá, DC, Colombia.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization, 2010. Guidelines for the Treatment of Malaria. Second edition. Available at: http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf. Accessed January 20, 2011.
-
2.
Premji ZG, 2009. Coartem: the journey to the clinic. Malar J 8 (Suppl 1): S3.
-
3.
Brewer TG, Peggins JO, Grate SJ, Petras JM, Levine BS, Weina PJ, Swearengen J, Heiffer MH, Schuster BG, 1994. Neurotoxicity in animals due to arteether and artemether. Trans R Soc Trop Med Hyg 88 (Suppl 1): S33–S36.
-
4.
Brewer TG, Grate SJ, Peggins JO, Weina PJ, Petras JM, Levine BS, Heiffer MH, Schuster BG, 1994. Fatal neurotoxicity of arteether and artemether. Am J Trop Med Hyg 51: 251–259.
-
5.
Petras JM, Kyle DE, Gettayacamin M, Young GD, Bauman RA, Webster HK, Corcoran KD, Peggins JO, Vane MA, Brewer TG, 1997. Arteether: risks of two-week administration in Macaca mulatta. Am J Trop Med Hyg 56: 390–396.
-
6.
Ribeiro IR, Olliaro P, 1998. Safety of artemisinin and its derivatives. A review of published and unpublished clinical trials. Med Trop 58 (Suppl 3): 50–53.
-
7.
Kissinger E, Hien TT, Hung NT, Nam ND, Tuyen NL, Dinh BV, Mann C, Phu NH, Loc PP, Simpson JA, White NJ, Farrar JJ, 2000. Clinical and neurophysiological study of the effects of multiple doses of artemisinin on brain-stem function in Vietnamese patients. Am J Trop Med Hyg 63: 48–55.
-
8.
Hien TT, Turner GD, Mai NT, Phu NH, Bethell D, Blakemore WF, Cavanagh JB, Dayan A, Medana I, Weller RO, Day NP, White NJ, 2003. Neuropathological assessment of artemether-treated severe malaria. Lancet 362: 295–296.
-
9.
Toovey S, Jamieson A, 2004. Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether. Trans R Soc Trop Med Hyg 98: 261–267.
-
10.
World Health Organization, 2000. Management of Severe Malaria: A Practical Handbook. Second edition. Available at: http://www.rollbackmalaria.org/docs/hbsm.pdf. Accessed January 20, 2011.
-
11.
World Health Organization, 2003. Assessment and Monitoring of Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria. Available at: http://whqlibdoc.who.int/hq/2003/WHO_HTM_RBM_2003.50.pdf. Accessed January 20, 2011.
-
12.
Felger I, Beck HP, 2002. Genotyping of Plasmodium falciparum: PCR-RFLP analysis. Doolan D, ed. Malaria Methods and Protocols: Methods in Molecular Medicine. Totawa, NJ: Humana Press, 117–129.
-
13.
Carhart R, Jerger J, 1959. Preferred method for clinical determination of pure-tone thresholds. J Speech Hear Disord 24: 330–345.
-
14.
Souppart C, Gauducheau N, Sandrenan N, Richard F, 2002. Development and validation of a high-performance liquid chromatography-mass spectrometry assay for the determination of artemether and its metabolite dihydroartemisinin in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 774: 195–203.
-
15.
Bergqvist Y, Hellgren U, Churchill FC, 1988. High-performance liquid chromatographic assay for the simultaneous monitoring of mefloquine and its acid metabolite in biological samples using protein precipitation and ion-pair extraction. J Chromatogr A 432: 252–263.
-
16.
Burkard RF, Don M, Eggermont JJ, 2007. Auditory Evoked Potentials: Basic Principles and Clinical Applications. Philadelphia, PA: Lippincott, Williams & Wilkins.
-
17.
Fausti SA, Flick CL, Bobal AM, Ellingson RM, Henry JA, Mitchell CR, 2003. Comparison of ABR stimuli for the early detection of ototoxicity: conventional clicks compared with high frequency clicks and single frequency tone bursts. J Am Acad Audiol 14: 239–250.
-
18.
Don M, Kwong B, 2002. Auditory brainstem response: differential diagnosis. Katz J, ed. Handbook of Clinical Audiology. Fifth edition. New York: Lippincott Williams & Wilkins, 274–297.
-
19.
Hecox K, Galambos R, 1974. Brain stem auditory evoked responses in human infants and adults. Arch Otolaryngol 99: 30–33.
-
20.
Clemis JD, Mc Gee T, 1979. Brain stem electric response audiometry in the differential diagnosis of acoustic tumors. Laryngoscope 89: 31–42.
-
21.
Bergholtz L, 1981. Normative data in clinical ABR. Scand Audiol Suppl 13: 75–81.
-
22.
Carrara VI, Phyo AP, Nwee P, Soe M, Htoo H, Arunkamomkiri J, Singhasivanon P, Nosten F, 2008. Auditory assessment of patients with acute uncomplicated Plasmodium falciparum malaria treated with three-day mefloquine-artesunate on the north-western border of Thailand. Malar J 7: 233.
-
23.
American Academy of Otolaryngology-Head and Neck Surgery Foundation, 1995. Committee on Hearing and Equilibrium guidelines for the evaluation of hearing preservation in acoustic neuroma (vestibular schwannoma). Otolaryngo Head Neck Surg 113: 179–180.
-
24.
Van Vugt M, Angus BJ, Price RN, Mann C, Simpson JA, Poletto C, Htoo SE, Looareesuwan S, White NJ, Nosten F, 2000. A case-control auditory evaluation of patients treated with artemisinin derivatives for multidrug-resistant Plasmodium falciparum malaria. Am J Trop Med Hyg 62: 65–69.
-
25.
Hutagalung R, Htoo H, Nwee P, Arunkamomkiri J, Zwang J, Carrara VI, Ashley E, Singhasivanon P, White NJ, Nosten F, 2006. A case-control auditory evaluation of patients treated with artemether-lumefantrine. Am J Trop Med Hyg 74: 211–214.
-
26.
McCall MB, Beynon AJ, Mylanus EA, van der Ven AJ, Sauerwein RW, 2006. No hearing loss associated with the use of artemether-lumefantrine to treat experimental human malaria. Trans R Soc Trop Med Hyg 100: 1098–1104.
-
27.
Gürkov R, Eshetu T, Miranda IB, Berens-Riha N, Mamo Y, Girma T, Krause E, Schmidt M, Hempel JM, Löscher T, 2008. Ototoxicity of artemether/lumefantrine in the treatment of falciparum malaria: a randomized trial. Malar J 7: 179.
-
28.
Mueller EA, van Vugt M, Kirch W, Andriano K, Hunt P, de Palacios PI, 2006. Efficacy and safety of the six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in adolescents and adults: a pooled analysis of individual patient data from randomized clinical trials. Acta Trop 100: 41–53.
-
29.
Mayxay M, Khanthavong M, Lindegårdh N, Keola S, Barends M, Pongvongsa T, Yapom R, Annerberg A, Phompida S, Phetsouvanh R, White NJ, Newton PN, 2004. Randomized comparison of chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in the Lao People's Democratic Republic. Clin Infect Dis 39: 1139–1147.
-
30.
Hutagalung R, Paiphun L, Ashley EA, McGready R, Brockman A, Thwai KL, Singhasivanon P, Jelinek T, White NJ, Nosten FH, 2005. A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand. Malar J 4: 46.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 22 | 22 | 6 |
| Full Text Views | 356 | 94 | 0 |
| PDF Downloads | 80 | 21 | 0 |