Seven Day Primaquine Treatment Is Safe, Noninferior to 14 Day Course

In patients with malaria who have normal levels of glucose-6-phosphate dehydrogenase (G6PD), 7-day primaquine was well tolerated and noninferior to 14-day primaquine, according to data published in the Lancet.

A randomized, double-blind, placebo-controlled, noninferiority trial (ClinicalTrials.gov identifier: NCT01814683) in 8 healthcare clinics enrolled 2336 patients aged ≥ 6 years with uncomplicated Plasmodium vivax malaria and normal G6PD levels. Participants were given standard blood schizonticidal treatment and randomly assigned (2:2:1) to receive 7 days of supervised primaquine (1.0 mg/kg/day), 14 days of supervised primaquine (0.5 mg/kg/day), or a placebo.

The symptomatic recurrent P vivax malaria incident rate was 0.18 (95% CI, 0.15-0.21) recurrences per person-year for 935 patients in the 7-day primaquine group and 0.16 (95% CI, 0.13-0.18) for the 937 patients in the 14-day primaquine group. This led to a difference of 0.02 (95% CI, −0.02 to 0.05; P =.3405) between the 2 groups. For the 464 patients in the placebo group, the incidence rate was 0.96 (95% CI, 0.83-1.08) recurrences per person-year. Within 42 days of starting treatment, potential drug-related serious adverse events were reported in 9 patients in the 7-day group, 1 in the 14-day group, and none from the placebo group.

However, roughly one-third of patients in the study did not complete a 1-year follow-up. Researchers noted that this should not affect the primary outcome incidence rate of recurrent P vivax parasitemia, however, “because the additional Ethiopian sites ensured that the total number of patient days of follow-up exceeded that required to achieve 80% power for non-inferiority.”

The investigators concluded that the efficacy of the 7-day course of primaquine was noninferior to the standard 14-day course in patients with normal G6PD. It also had an acceptable tolerability and safety profile. They also believed that this reduced treatment time “has the potential to improve adherence and therefore the effectiveness of radical cure in [P vivax]-endemic countries.” The investigators cautioned, however, that the high-dose 7-day regime requires that G6PD deficiency can be reliably excluded.

Reference

Taylor WRJ, Thriemer K, von Seidlein L, et al. Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial [published online July 18, 2019]. Lancet. doi:10.1016/S0140-6736(19)31285-1