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Randomized Controlled Trial
. 2012 Mar 30:11:97.
doi: 10.1186/1475-2875-11-97.

Artesunate-amodiaquine fixed dose combination for the treatment of Plasmodium falciparum malaria in India

Anupkumar R Anvikar  1 , Bhawna Sharma, Bhartendu H Shahi, Prajesh K Tyagi, Tarit K Bose, Surya K Sharma, Prakriti Srivastava, Bina Srivastava, Jean R Kiechel, Aditya P Dash, Neena Valecha
Affiliations
Randomized Controlled Trial

Artesunate-amodiaquine fixed dose combination for the treatment of Plasmodium falciparum malaria in India

Anupkumar R Anvikar et al. Malar J. .

Abstract

Background: Artemisinin-based combination therapy (ACT) has been recommended for the treatment of falciparum malaria by the World Health Organization. Though India has already switched to ACT for treating falciparum malaria, there is need to have multiple options of alternative forms of ACT. A randomized trial was conducted to assess the safety and efficacy of the fixed dose combination of artesunate-amodiaquine (ASAQ) and amodiaquine (AQ) for the treatment of uncomplicated falciparum malaria for the first time in India. The study sites are located in malaria-endemic, chloroquine-resistant areas.

Methods: This was an open label, randomized trial conducted at two sites in India from January 2007 to January 2008. Patients between six months and 60 years of age having Plasmodium falciparum mono-infection were randomly allocated to ASAQ and AQ arms. The primary endpoint was 28-day PCR-corrected parasitological cure rate.

Results: Three hundred patients were enrolled at two participating centres, Ranchi, Jharkhand and Rourkela, Odisha. Two patients in AQ arm had early treatment failure while there was no early treatment failure in ASAQ arm. Late treatment failures were seen in 13 and 12 patients in ASAQ and AQ arms, respectively. The PCR-corrected cure rates in intent-to-treat population were 97.51% (94.6-99.1%) in ASAQ and 88.65% (81.3-93.9%) in AQ arms. In per-protocol population, they were 97.47% (94.2-99.2%) and 88.30% (80-94%) in ASAQ and AQ arms respectively. Seven serious adverse events (SAEs) were reported in five patients, of which two were reported as related to the treatment. All SAEs resolved without sequel.

Conclusion: The fixed dose combination of ASAQ was found to be efficacious and safe treatment for P. falciparum malaria. Amodiaquine also showed acceptable efficacy, making it a suitable partner of artesunate. The combination could prove to be a viable option in case India opts for fixed dose combination ACT.

Clinical trial registry: ISRCTN84408319.

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Figures

Figure 1
Figure 1
Map of India showing the study sites.
Figure 2
Figure 2
Participant flow.
Figure 3
Figure 3
Survival curve (Kaplan Meier plots) of Parasite Clearance Time (ITT population).
Figure 4
Figure 4
Survival curve (Kaplan Meier plots) of Fever Clearance Time (ITT population).
See this image and copyright information in PMC

References

    1. World Health Organization. Guidelines for the treatment of malaria. Second Edition. WHO, Geneva, Switzerland; 2010. http://www.who.int/malaria/publications/atoz/9789241547925/en/index.html
    1. National Vector Borne Disease Control Programme. National drug policy on malaria. Directorate of Health Services, Government of India; 2010. http://nvbdcp.gov.in/Doc/drug-policy-2010.pdf
    1. Ahmed A, Bararia D, Vinayak S, Yameen M, Biswas S, Dev V, Kumar A, Ansari AM, Sharma YD. Plasmodium falciparum isolates in India exhibit a progressive increase in mutations associated with sulfadoxine-pyrimethamine resistance. Antimicrob Agents Chemother. 2004;48:879–889. doi: 10.1128/AAC.48.3.879-889.2004. - DOI - PMC - PubMed
    1. Shah NK, Dhillon GP, Dash AP, Arora U, Meshnick SR, Valecha N. Antimalarial drug resistance of Plasmodium falciparum in India: changes over time and space. Lancet Infect Dis. 2011;11:57–64. doi: 10.1016/S1473-3099(10)70214-0. - DOI - PMC - PubMed
    1. Adjuik M, Agnamey P, Babiker A, Borrmann S, Brasseur P, Cisse M, Cobelens F, Diallo S, Faucher JF, Garner P, Gikunda S, Kremsner PG, Krishna S, Lell B, Loolpapit M, Matsiegui PB, Missinou MA, Mwanza J, Ntoumi F, Olliaro P, Osimbo P, Rezbach P, Some E, Taylor WR. Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised multicentre trial. Lancet. 2002;359:1365–1372. doi: 10.1016/S0140-6736(02)08348-4. - DOI - PubMed

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