Dihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trial.
BACKGROUND
Artemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children.


RESULTS
The non-inferiority of DHA-PQP versus artemether-lumefantrine (AL) in children 6-59 months old with uncomplicated P. falciparum malaria was tested in five African countries (Burkina Faso, Kenya, Mozambique, Uganda and Zambia). Patients were randomised (2:1) to receive either DHA-PQP or AL. Non-inferiority was assessed using a margin of -5% for the lower limit of the one-sided 97.5% confidence interval on the treatment difference (DHA-PQP vs. AL) of the day 28 polymerase chain reaction (PCR) corrected cure rate. Efficacy analysis was performed in several populations, and two of them are presented here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 1553 children were randomised, 1039 receiving DHA-PQP and 514 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% (ePP) in the AL group. The lower limits of the one-sided 97.5% CI of the difference between the two treatments were -2.80% and -2.96%, in the ITT and ePP populations, respectively. In the ITT population, the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55% (95% CI: 11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI: 20.11%-27.88%) for AL (p<0.0001).


CONCLUSIONS
DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity settings, and shows a comparable safety profile. The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group, indicating a longer post-treatment prophylactic effect.


BACKGROUND
Controlled-trials.com ISRCTN16263443.
Bassat
Quique
Q
Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain.
Mulenga
Modest
M
Tinto
Halidou
H
Piola
Patrice
P
Borrmann
Steffen
S
Menéndez
Clara
C
Nambozi
Michael
M
Valéa
Innocent
I
Nabasumba
Carolyn
C
Sasi
Philip
P
Bacchieri
Antonella
A
Corsi
Marco
M
Ubben
David
D
Talisuna
Ambrose
A
D'Alessandro
Umberto
U
D000349:Africa; D000977:Antiparasitic Agents / Q000494:pharmacology; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology*; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000379:methods; D004983:Ethanolamines / Q000494:pharmacology*; D005449:Fluorenes / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D000078102:Lumefantrine; D008288:Malaria / Q000188:drug therapy*; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011804:Quinolines / Q000494:pharmacology*; D013997:Time Factors; D010879:Piperazines
D000977:Antiparasitic Agents; D000077549:Artemether; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D000078102:Lumefantrine; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines