1. Efficacy and Safety of a Naphthoquine-Azithromycin Coformulation for Malaria Prophylaxis in Southeast Asia: A Phase 3, Double-blind, Randomized, Placebo-controlled Trial.
- Author
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Yang H, Wang J, Liu H, Zhao Y, Lakshmi S, Li X, Nie R, Li C, Wang H, Cao Y, Menezes L, and Cui L
- Subjects
- 1-Naphthylamine analogs & derivatives, Adolescent, Adult, Aged, Aminoquinolines, Asia, Southeastern, Azithromycin adverse effects, Child, Child, Preschool, Double-Blind Method, Humans, Middle Aged, Young Adult, Antimalarials adverse effects, Malaria drug therapy, Malaria prevention & control, Malaria, Falciparum drug therapy, Malaria, Falciparum epidemiology, Malaria, Falciparum prevention & control, Malaria, Vivax drug therapy, Malaria, Vivax epidemiology, Malaria, Vivax prevention & control
- Abstract
Background: A prophylactic antimalarial drug that is both effective for protection and improves compliance is in high demand., Methods: We conducted a randomized, placebo-controlled, double-blinded phase 3 trial to evaluate the 1:1 fixed-dose combination of naphthoquine-azithromycin (NQAZ) for safety and protection against Plasmodium infections in villages along the China-Myanmar border. A total of 631 residents, 5-65 years of age, were randomized into the drug group (n = 319) and the placebo group (n = 312) to receive NZAQ and placebo, respectively, as a single-dose monthly treatment. Follow-ups were conducted weekly to monitor for adverse events and malaria infections., Results: Of the 531 subjects completing the trial, there were 46 and 3 blood smear-positive Plasmodium infections in the placebo and treatment groups, respectively. For the intent-to-treat analysis, the single-dose monthly NQAZ treatment had 93.62% protective efficacy (95% confidence interval [CI]: 91.72%-95.52%). For the per-protocol analysis, NQAZ treatment provided a 93.04% protective efficacy (95% CI: 90.98%-95.1%). Three smear-positive cases in the NQAZ group were all due to acute falciparum malaria. In comparison, NQAZ treatment provided 100% protection against the relapsing malaria Plasmodium vivax and Plasmodium ovale. The treatment group had 5.6% of participants experiencing transient elevation of liver aminotransferases compared with 2.2% in the placebo group (P > .05)., Conclusions: Monthly prophylaxis with NQAZ tablets was well tolerated and highly effective for preventing Plasmodium infections. It may prove useful for eliminating P. vivax in areas with a high prevalence of glucose-6-phosphate dehydrogenase deficiency in the population., Clinical Trials Registration: ChiCTR1800020140., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2021
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