Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial

Table 2 Adequate clinical and parasitological response (ACPR) in the per-protocol population

Outcome	Pyronaridine-artesunate	Artemether-lumefantrine	Difference (95% CI);
Outcome	Pyronaridine-artesunate	Artemether-lumefantrine	P value^a
Day-28 PCR-corrected ACPR,^b n/N	329/339	165/167
% (95% CI)	97.1 (94.6–98.6)	98.8 (95.7–99.9)	–1.8 (–4.3 to 1.6); P = .22
P value (exact binomial test)^c	<.0001	NC
Total failures	10 (2.9)	2 (1.2)
Early treatment failure	2 (0.6)	0
Late clinical failure	2 (0.6)	0
Late parasitological failure	6 (1.8)	2 (1.2)
Day-28 crude ACPR, n/N	305/341	149/172
% (95% CI)	89.4 (85.7–92.5)	86.6 (80.6–91.3)	2.8 (–2.9 to 9.4); P = .35
Total failures	36 (10.6)	23 (13.4)
Early treatment failure	2 (0.6)	0
Late clinical failure	6 (1.8)	4 (2.3)
Late parasitological failure	28 (8.2)	19 (11.0)
Day-42 PCR-corrected ACPR,^b n/N	257/275	133/139
% (95% CI)	93.5 (89.9–96.1)	95.7 (90.8–98.4)	–2.2 (–6.5 to 3.1); P = .36
Total failures	18 (6.5)	6 (4.3)
Early treatment failure	2 (0.7)	0
Late clinical failure	2 (0.7)	0
Late parasitological failure	14 (5.1)	6 (4.3)
Day-42 crude ACPR, n/N	249/325	130/166
% (95% CI)	76.6 (71.6–81.1)	78.3 (71.3–84.3)	–1.7 (–9.1 to 6.4); P = .67
Total failures	76 (23.4)	36 (21.7)
Early treatment failure	2 (0.6)	0
Late clinical failure	14 (4.3)	5 (3.0)
Late parasitological failure	60 (18.5)	31 (18.7)

NC, not calculated. Values are n (%) unless otherwise indicated.
^a Non-inferiority of pyronaridine-artesunate to artemether-lumefantrine is concluded if the lower limit of the 95% CI for the difference is > –10%. Two-sided Chi-square test for superiority was performed only when non-inferiority was demonstrated.
^b Corrected for re-infection using polymerase chain reaction (PCR) genotyping.
^c For the hypothesis that the ACPR in the pyronaridine-artesunate group is ≤90%.
Note: There were no instances of indeterminate PCR results in the per-protocol population.
Per-protocol population: The per-protocol population was defined by time point (day 28 and day 42) and by endpoint (PCR-corrected ACPR versus crude ACPR). Patients with a new infection (re-infection) before day 28 were included in the day-28 per-protocol population for the crude analysis (failures). However, in the PCR-corrected analysis, patients with re-infection before day 28 were excluded owing to missing data at day 28, i.e. they were not deemed a failure (recrudescence) before day 28 and had missing data for this time point. The day-42 per-protocol population was defined similarly.

ISSN: 1475-2875