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 old, were randomized into the drug group (319) and the placebo group (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 transaminases as compared to 2.2% in the placebo group (P > 0.05).
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.
Final efficacy analysis, interim safety analysis, and immunogenicity of a single dose of recombinant novel coronavirus vaccine (adenovirus type 5 vector) in adults 18 years and older: an international, multicentre, randomised, double-blinded, placebo-controlled phase 3 trial
