Llanos-Cuentas A, et al. - Among subjects with normal glucose-6-phosphate dehydrogenase (G6PD) enzyme activity, investigators examined the comparative efficiency of tafenoquine and primaquine for the radical cure of Plasmodium vivax malaria. They observed tafenoquine more effective for the radical cure of P. vivax malaria although, no significant difference in hemoglobin level reduction between tafenoquine and primaquine administered groups was noticed.

Methods

• A phase 3, prospective, double-blind, double-dummy, randomized, controlled trial was conducted to assess the comparative efficiency and safety of tafenoquine with primaquine.
• They included subjects with normal glucose-6-phosphate dehydrogenase (G6PD) enzyme activity (female candidates with moderate G6PD enzyme deficiency) and confirmed P. vivax parasitemia in the trial conducted at 7 hospitals or clinics in Peru, Brazil, Colombia, Vietnam, and Thailand.
• They categorized the candidates in a 2:1 ratio, to receive a single 300-mg dose of tafenoquine or 15 mg of primaquine once daily for 14 days (administered under supervision).
• All individuals were given a 3-day course of chloroquine and were followed for 180 days.
• A protocol-defined decline in the hemoglobin level (>3.0 g per deciliter or ≥30% from baseline or to a level of <6.0 g per deciliter) was considered as the primary safety outcome.
• They used an odds ratio for recurrence of 1.45 (tafenoquine vs primaquine) as a noninferiority margin whereas freedom from recurrence of P. vivax parasitemia at 6 months was the primary efficiency outcome in a planned patient-level meta-analysis of this trial and another phase 3 trial of tafenoquine and primaquine (per-protocol populations).

Results

• For a between-group difference of 1.2 percentage points (95% CI, −4.2 to 5.0), they observed a protocol-defined decline in the hemoglobin level took place in 4 of 166 subjects (2.4%; 95% confidence interval [CI], 0.9 to 6.0) in the tafenoquine group and in 1 of 85 candidates (1.2%; 95% CI, 0.2 to 6.4) in the primaquine group.
• They noticed 67.0% (95% CI, 61.0 to 72.3) among 426 candidates in tafenoquine group and 72.8% (95% CI, 65.6 to 78.8) among 214 subjects in primaquine group were free from recurrence at 6 months.
• They did not found the efficiency of tafenoquine to be noninferior to that of primaquine (odds ratio for recurrence, 1.81; 95% CI, 0.82 to 3.96).