The online version of this article (https://doi.org/10.1186/s12936-018-2192-x) contains supplementary material, which is available to authorized users.
There is general international agreement that the importance of vivax malaria has been neglected, and there is a need for new treatment approaches in an effort to progress towards control and elimination in Latin America. This open label randomized clinical trial evaluated the efficacy and safety of three treatment regimens using either one of two fixed dose artemisinin-based combinations or chloroquine in combination with a short course of primaquine (7–9 days: total dose 3–4.2 mg/kg) in Brazil. The primary objective was establishing whether cure rates above 90% could be achieved in each arm.
A total of 264 patients were followed up to day 63. The cure rate of all three treatment arms was greater than 90% at 28 and 42 days. Cure rates were below 90% in all three treatment groups at day 63, although the 95% confidence interval included 90% for all three treatments. Most of the adverse events were mild in all treatment arms. Only one of the three serious adverse events was related to the treatment and significant drops in haemoglobin were rare.
This study demonstrated the efficacy and safety of all three regimens that were tested with 42-day cure rates that meet World Health Organization criteria. The efficacy and safety of artemisinin-based combination therapy regimens in this population offers the opportunity to treat all species of malaria with the same regimen, simplifying protocols for malaria control programmes and potentially contributing to elimination of both vivax and falciparum malaria.
Trial registration RBR-79s56s
Additional file 1: Table S1. Reasons to not be included—Consort Diagram.
Additional file 2: Table S2. Distribution of use of concomitant medication (grouped in therapeutic class) in each study arm, parenthesis presents the percentage of the line. Figure S1. Distribution of most frequent medications used per study visit and treatment group.
Additional file 3: Table S3. Proportion of treatment success per treatment arm in ITT population (n = 88 per arm) at day 28, 42 and 63. Table S4. Proportion of treatment success per treatment arm in PP population at day 07, 14 and 21. Table S5. Proportion of treatment success per treatment arm in ITT population (n = 88 per arm) at day 07, 14 and 21.
Additional file 4: Table S6. Distribution of adverse events per causality and treatment group.
Additional file 5: Table S7. Distribution of adverse events per causality and intensity (grade) in the treatment group ASMQ + Pq. Table S8. Distribution of adverse events per causality and intensity (grade) in the treatment group CQ + Pq. Table S9. Distribution of adverse events per causality and intensity (grade) in the treatment group AL + Pq.
Additional file 6: Table S10. All adverse events (1593) per body system and treatment allocation.
Additional file 7: Table S11. Adverse events with frequency higher than 3% in the ASMQ + Pq arm (n total = 403). Table S12. Adverse events with frequency higher than 3% in the CQ + Pq arm (n total = 643). Table S13. Adverse events with frequency higher than 3% in the AL + Pq arm (n total = 547).
Additional file 8: Table S14. Haemoglobin mean per regimen allocation at day 0, 14, 28, 42, and 63.
WHO. Control and elimination of vivax malaria: a technical brief. Geneva: World Health Organization; 2015.
Secretaria de Vigilância em Saúde. Malária: Monitoramento dos casos no Brasil em 2014. Boletim Epidemiológico Secretaria de Vigilância em Saúde Ministério da Saúde; 2015. p. 46.
Kochar DK, Das A, Kochar SK, Saxena V, Sirohi P, Garg S, et al. Severe Plasmodium vivax malaria: a report on serial cases from Bikaner in northwestern India. Am J Trop Med Hyg. 2009;80:194–8. PubMed
Ministério da Saúde do Brasil. Guia prático de tratamento de malária. In: Série A Normas e Manuais Técnicos. Secretária de Vigilância em Saúde—Ministério da Saúde do Brasil; 2010. http://www.saude.gov.br/bvs. Accessed June 2017.
Pereira D, Daher A, Zanini G, Maia I, Fonseca L, Pitta L, et al. Safety, efficacy and pharmacokinetic evaluations of a new coated chloroquine tablet in a single-arm open-label non-comparative trial in Brazil: a step towards a user-friendly malaria vivax treatment. Malar J. 2016;15:477. CrossRefPubMedPubMedCentral
WHO. Methods for surveillance of antimalarial drug efficacy. Geneva: World Health Organization; 2009.
ICH. Good clinical practice. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. 1996. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf. Accessed June 2017.
Pan American Health Organization. Boas Práticas Clínicas: Documento das Américas. Washington, DC: Pan American Health Organization WHO; 2005. http://www.anvisa.gov.br/medicamentos/pesquisa/boaspraticas_americas.pdf. Accessed June 2017.
NCI common terminology criteria for adverse events. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm-ctc_40. Accessed June 2017.
WHO. Guidelines for the treatment of malaria. 2nd ed. Geneva: World Health Organization; 2010.
Gogtay N, Kannan S, Thatte UM, Olliaro PL, Sinclair D. Artemisinin-based combination therapy for treating uncomplicated Plasmodium vivax malaria. Cochrane Database Syst Rev. 2013;(10):CD008492. https://doi.org/10.1002/14651858.CD008492.pub3. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008492.pub3/abstract;jsessionid=49E497269900A8965B3F62DEEB6D81A5.f02t02. Accessed 18 Jan 2018.
- Efficacy and safety of artemisinin-based combination therapy and chloroquine with concomitant primaquine to treat Plasmodium vivax malaria in Brazil: an open label randomized clinical trial
Marcus V. G. Lacerda
Márcia A. A. Alexandre
Cristiana T. Nascimento
Júlio Castro Alves de Lima e Silva
Tereza Cristina dos Santos
Ana Carolina Santelli
David G. Lalloo
- BioMed Central
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