Efficacy and safety of artemisinin-naphthoquine versus dihydroartemisinin-piperaquine in adult patients with uncomplicated malaria: a multi-centre study in Indonesia

Malaria Journal, Jun 2012

Background A practical and simple regimen for all malaria species is needed towards malaria elimination in Indonesia. It is worth to compare the efficacy and safety of a single dose of artemisinin-naphthoquine (AN) with a three-day regimen of dihydroartemisinin-piperaquine (DHP), the existing programme drug, in adults with uncomplicated symptomatic malaria. Methods This is a phase III, randomized, open label using sealed envelopes, multi-centre, comparative study between a single dose of AN and a three-day dose of DHP in Jayapura and Maumere. The modified WHO inclusion and exclusion criteria for efficacy study were used in this trial. A total of 401 eligible adult malaria subjects were hospitalized for three days and randomly treated with AN four tablets single dose on day 0 or DHP three to four tablets single daily dose for three days, and followed for 42 days for physical examination, thick and thin smears microscopy, and other necessary tests. The efficacy of drug was assessed by polymerase chain reaction (PCR) uncorrected and corrected. Results There were 153 Plasmodium falciparum, 158 Plasmodium vivax and 90 P. falciparum/P. vivax malaria. Mean of fever clearance times were similar, 13.0 ± 10.3 hours in AN and 11.3 ± 7.3 hours in DHP groups. The mean of parasite clearance times were longer in AN compared with DHP (28.0 ± 11.7 hours vs 25.5 ± 12.2 hours, p = 0.04). There were only 12 PCR-corrected P. falciparum late treatment failures: seven in AN and five in DHP groups. The PCR uncorrected and corrected on day −42 of adequate clinical and parasitological responses for treatment of any malaria were 93.7% (95% Cl: 90.3–97.2) and 96.3% (95% Cl: 93.6–99.0) in AN, 96.3% (95% Cl: 93.5–99.0) and 97.3% (95% Cl: 95.0–99.6) in DHP groups. Few and mild adverse events were reported. All the abnormal haematology and blood chemistry values had no clinical abnormality. Conclusion AN and DHP are confirmed very effective, safe and tolerate for treatment of any malaria. Both drugs are promising for multiple first-line therapy policies in Indonesia.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://www.malariajournal.com/content/pdf/1475-2875-11-153.pdf

Efficacy and safety of artemisinin-naphthoquine versus dihydroartemisinin-piperaquine in adult patients with uncomplicated malaria: a multi-centre study in Indonesia

Malaria Journal Efficacy and safety of artemisinin-naphthoquine versus dihydroartemisinin-piperaquine in adult patients with uncomplicated malaria: a multi-centre study in Indonesia Emiliana Tjitra 2 Armedy R Hasugian 2 Hadjar Siswantoro 2 Budi Prasetyorini 2 Riyanti Ekowatiningsih 2 Endah A Yusnita 2 Telly Purnamasari 2 Srilaning Driyah 2 Ervi Salwati 2 Nurhayati 2 Eni Yuwarni 2 Lidwina Januar 1 Joseph Labora 0 Bambang Wijayanto 6 Fajar Amansyah 5 Tersila AD Dedang 4 Asep Purnama 3 Trihono 2 0 Marthen Indeys Army Hospital , Jayapura, Papua , Indonesia 1 Centre for Biomedical Research and Development , Jayapura, Papua , Indonesia 2 National Institute of Health Research and Development, Ministry of Health , Jakarta , Indonesia 3 TC Hillers District Public Hospital , Maumere, Sikka, East Nusa Tenggara , Indonesia 4 Kewapante Catholic Hospital , Maumere, Sikka, East Nusa Tenggara , Indonesia 5 Bhayangkara Police Hospital , Jayapura, Papua , Indonesia 6 Soedibjo Sardadi Navy Hospital , Jayapura, Papua , Indonesia Background: A practical and simple regimen for all malaria species is needed towards malaria elimination in Indonesia. It is worth to compare the efficacy and safety of a single dose of artemisinin-naphthoquine (AN) with a three-day regimen of dihydroartemisinin-piperaquine (DHP), the existing programme drug, in adults with uncomplicated symptomatic malaria. Methods: This is a phase III, randomized, open label using sealed envelopes, multi-centre, comparative study between a single dose of AN and a three-day dose of DHP in Jayapura and Maumere. The modified WHO inclusion and exclusion criteria for efficacy study were used in this trial. A total of 401 eligible adult malaria subjects were hospitalized for three days and randomly treated with AN four tablets single dose on day 0 or DHP three to four tablets single daily dose for three days, and followed for 42 days for physical examination, thick and thin smears microscopy, and other necessary tests. The efficacy of drug was assessed by polymerase chain reaction (PCR) uncorrected and corrected. Results: There were 153 Plasmodium falciparum, 158 Plasmodium vivax and 90 P. falciparum/P. vivax malaria. Mean of fever clearance times were similar, 13.0 10.3 hours in AN and 11.3 7.3 hours in DHP groups. The mean of parasite clearance times were longer in AN compared with DHP (28.0 11.7 hours vs 25.5 12.2 hours, p = 0.04). There were only 12 PCR-corrected P. falciparum late treatment failures: seven in AN and five in DHP groups. The PCR uncorrected and corrected on day 42 of adequate clinical and parasitological responses for treatment of any malaria were 93.7% (95% Cl: 90.3-97.2) and 96.3% (95% Cl: 93.6-99.0) in AN, 96.3% (95% Cl: 93.5-99.0) and 97.3% (95% Cl: 95.0-99.6) in DHP groups. Few and mild adverse events were reported. All the abnormal haematology and blood chemistry values had no clinical abnormality. Conclusion: AN and DHP are confirmed very effective, safe and tolerate for treatment of any malaria. Both drugs are promising for multiple first-line therapy policies in Indonesia. Malaria; Artemisinin-naphthoquine; Dihydroartemisinin-piperaquine; Efficacy; Safety - Background Malaria remains a major public health problem. The World Health Organization (WHO) estimated the number of reported cases from Indonesia were 2.5 million in 2006 [1]. Most cases were recorded from Papua and East Nusa Tenggara provinces, where about 300,000 and 70,000 clinical malaria cases were reported annually from its provinces. To accelerate malaria control, one of the four key recommended interventions is to give appropriate antimalarial drugs with artemisinin-based combination therapy (ACT) for patients with confirmed malaria [1]. Artemisinin was discovered by Chinese scientists in the 1970s. Artemisinin derivatives are the most rapidly acting and efficacious anti-malarial drugs. These drugs show rapid absorption and activity against many stages of Plasmodium, including trophozoites and early sexual forms (gametocytes). Their short elimination half-life (<3.7 hours) protects them from resistance and their potent and broad specificity of action reduces gametocyte carriage and infectivity, and reduces the transmission of Plasmodium falciparum. Tolerability of these drugs is also very good [2,3]. This makes artemisinin derivatives the ideal partner drugs. WHO recommends the use of artemisinins only in combination with another anti-malarial drug to prevent the occurrence of drug resistance and to address the issue of its relatively short half-life. ACT is the best therapeutic option for treating drug-resistant malaria and retarding the development of resistance presently [4]. Since 2004, the Indonesian Malaria Control Programme has chosen a non-fixed dose artesunate-amodiaquine (AA) as the programme drug for treatment of uncomplicated P. falciparum, which had widely reported resistant to chloroquine, sulphadoxine-pyrimethamine or quinine [5]. AA is also effective for (...truncated)


This is a preview of a remote PDF: http://www.malariajournal.com/content/pdf/1475-2875-11-153.pdf

Emiliana Tjitra, Armedy R Hasugian, Hadjar Siswantoro, Budi Prasetyorini, Riyanti Ekowatiningsih, Endah A Yusnita, Telly Purnamasari, Srilaning Driyah, Ervi Salwati, , Eni Yuwarni, Lidwina Januar, Joseph Labora, Bambang Wijayanto, Fajar Amansyah, Tersila AD Dedang, Asep Purnama, . Efficacy and safety of artemisinin-naphthoquine versus dihydroartemisinin-piperaquine in adult patients with uncomplicated malaria: a multi-centre study in Indonesia, Malaria Journal, 2012, pp. 153, 11, DOI: 10.1186/1475-2875-11-153