Muhindo Mavoko, Hypolite and Nabasumba, Carolyn and Inocêncio da Luz, Raquel and Tinto, Halidou and D’Alessandro, Umberto and Kambugu, Andrew and Baraka, Vito and Rosanas-Urgell, Anna and Lutumba, Pascal and Van geertruyden, Jean-Pierre (2017) Effi cacy and safety of re-treatment with the same artemisinin-based combination treatment (ACT) compared with an alternative ACT and quinine plus clindamycin after failure of fi rst-line recommended ACT (QUINACT): a bicentre, open-label, phase 3, randomised controlled trial. The Lancet Global Health, 5 (1). e60-e68. ISSN 0140-6736
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Abstract
Background Quinine or alternative artemisinin-based combination treatment (ACT) is the recommended rescue treatment for uncomplicated malaria. However, patients are often re-treated with the same ACT though it is unclear whether this is the most suitable approach. We assessed the effi cacy and safety of re-treating malaria patients with uncomplicated failures with the same ACT used for the primary episode, compared with other rescue treatments. Methods This was a bicentre, open-label, randomised, three-arm phase 3 trial done in Lisungi health centre in DR Congo, and Kazo health centre in Uganda in 2012–14. Children aged 12–60 months with recurrent malaria infection after treatment with the fi rst-line ACT were randomly assigned to either re-treatment with the same fi rst-line ACT, an alternative ACT, which were given for 3 days, or quinine-clindamycin (QnC), which was given for 5–7 days, following a 2:2:1 ratio. Randomisation was done by computer-generated randomisation list in a block design by country. The three treatment groups were assumed to have equivalent effi cacy above 90%. Both the research team and parents or guardians were aware of treatment allocation. The primary outcome was the proportion of patients with an adequate clinical and parasitological response (ACPR) at day 28, in the per-protocol population. This trial was registered under the numbers NCT01374581 in ClinicalTrials.gov and PACTR201203000351114 in the Pan African Clinical Trials Registry. Findings From May 22, 2012, to Jan 31, 2014, 571 children were included in the trial. 240 children were randomly assigned to the re-treatment ACT group, 233 to the alternative ACT group, and 98 to the QnC group. 500 children were assessed for the primary outcome. 71 others were not included because they did not complete the follow-up or PCR genotyping result was not conclusive. The ACPR response was similar in the three groups: 91·4% (95% CI 87·5–95·2) for the re-treatment ACT, 91·3% (95% CI 87·4–95·1) for the alternative ACT, and 89·5% (95% CI 83·0–96·0) for QnC. The estimates for rates of malaria recrudescence in the three treatment groups were similar (log-rank test: χ²=0·22, p=0·894). Artemether-lumefantrine was better tolerated than QnC (p=0·0005) and artesunateamodiaquine (p<0·0001) in the modifi ed intention-to-treat analysis. No serious adverse events were observed. The most common adverse events reported in the re-treatment ACT group were anorexia (31 [13%] of 240 patients), asthenia (20 [8%]), coughing (16 [7%]), abnormal behaviour (13 [5%]), and diarrhoea (12 [5%]). Anorexia (13 [6%] of 233 patients) was the most frequently reported adverse event in the alternative ACT group. The most commonly reported adverse events in the QnC group were anorexia (12 [12%] of 98 patients), abnormal behaviour (6 [6%]), asthenia (6 [6%]), and pruritus (5 [5%]). Interpretation Re-treatment with the same ACT shows similar effi cacy as recommended rescue treatments and could be considered for rescue treatment for Plasmodium falciparum malaria. However, the eff ect of this approach on the selection of resistant strains should be monitored to ensure that re-treatment with the same ACT does not contribute to P falciparum resistance.
| Item Type: | Article |
|---|---|
| Subjects: | WA Public Health |
| Divisions: | Faculty of Medicin |
| Depositing User: | Touba Derakhshande |
| Date Deposited: | 17 Sep 2017 06:24 |
| Last Modified: | 17 Sep 2017 06:24 |
| URI: | http://eprints.bpums.ac.ir/id/eprint/5981 |
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