Efficacy and safety of a fixed dose artesunate-sulphamethoxypyrazine-pyrimethamine compared to artemether-lumefantrine for the treatment of uncomplicated falciparum malaria across Africa: a randomized multi-centre trial.
BACKGROUND
The efficacy of artemisinin-based combination therapy has already been demonstrated in a number of studies all over the world, and some of them can be regarded as comparably effective. Ease of administration of anti-malarial treatments with shorter courses and fewer tablets may be key determinant of compliance.


METHODS
Patients with uncomplicated falciparum malaria and over six months of age were recruited in Cameroon, Mali, Rwanda and Sudan. 1,384 patients were randomly assigned to receive artesunate-sulphamethoxypyrazine-pyrimethamine (AS-SMP) three-day (once daily for 3 days) regimen (N = 476) or AS-SMP 24-hour (0 h, 12 h, 24 h) regimen (N = 458) or artemether-lumefantrine (AL), the regular 6 doses regimen (N = 450). The primary objective was to demonstrate non-inferiority (using a margin of -6%) of AS-SMP 24 hours or AS-SMP three days versus AL on the PCR-corrected 28-day cure rate.


RESULTS
The PCR corrected 28-day cure rate on the intention to treat (ITT) analysis population were: 96.0%(457/476) in the AS-SMP three-day group, 93.7%(429/458) in the AS-SMP 24-hour group and 92.0%(414/450) in the AL group. Likewise, the cure rates on the PP analysis population were high: 99.3%(432/437) in the AS-SMP three-day group, 99.5%(416/419) in the AS-SMP 24-hour group and 99.7(391/394)% in the AL group. Most common drug-related adverse events were gastrointestinal symptoms (such as vomiting and diarrhea) which were slightly higher in the AS-SMP 24-hour group.


CONCLUSIONS
AS-SMP three days or AS-SMP 24 hours are safe, are as efficacious as AL, and are well tolerated.


BACKGROUND
NCT00484900 http://www.clinicaltrials.gov.
Sagara
Issaka
I
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto-Stomatology, University of Bamako, Bamako, Mali. isagara@mrtcbko.org
Rulisa
Stephen
S
Mbacham
Wilfred
W
Adam
Ishag
I
Sissoko
Kourane
K
Maiga
Hamma
H
Traore
Oumar B
OB
Dara
Niawanlou
N
Dicko
Yahia T
YT
Dicko
Alassane
A
Djimdé
Abdoulaye
A
Jansen
F Herwig
FH
Doumbo
Ogobara K
OK
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D011247:Pregnancy; D011446:Prospective Studies; D011739:Pyrimethamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013415:Sulfalene / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013607:Tablets; D016896:Treatment Outcome
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D013607:Tablets; D000077332:Artesunate; D013415:Sulfalene; D011739:Pyrimethamine