Henglin Yang1, Jingyan Wang2, Hui Liu1, Yan Zhao3, Seetha Lakshmi4, Xingliang Li1, Renhua Nie1, Chunfu Li1, Hengye Wang1, Yaming Cao3, Lynette Menezes4, Liwang Cui4. 1. Yunnan Institute of Parasitic Diseases, Yunnan Provincial Center of Malaria Research, Pu'er, Yunnan, China. 2. Institute of Microbiology and Epidemiology, Chinese Academy of Military Medical Sciences, Beijing, China. 3. Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China. 4. Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
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.
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.
Authors: Heng Yan Qu; Hong Zhi Gao; Guang Tao Hao; Yuan Yuan Li; Hai Yan Li; Jin Chao Hu; Xiao Fang Wang; Wei Li Liu; Ze Yuan Liu Journal: J Clin Pharmacol Date: 2010-03-02 Impact factor: 3.126
Authors: W R Taylor; T L Richie; D J Fryauff; H Picarima; C Ohrt; D Tang; D Braitman; G S Murphy; H Widjaja; E Tjitra; A Ganjar; T R Jones; H Basri; J Berman Journal: Clin Infect Dis Date: 1999-01 Impact factor: 9.079