The comparative efficacy and tolerability of CGP 56697 (artemether + lumefantrine) versus halofantrine in the treatment of uncomplicated falciparum malaria in travellers returning from the Tropics to The Netherlands and France.
CGP 56697 (Riamet) is a new oral anti-malarial drug composed of artemether and lumefantrine (benflumetol) which combines the fast, short-acting artemether for rapid parasite clearance with the prolonged action of lumefantrine for intended radical cure. In this double-blind, comparative trial, the efficacy and tolerability of CGP 56697, given as a course of 4 x 4 tablets over 48 h, was compared to halofantrine, given as 3 x 2 tablets over 12 h with a second course 1 week later. Patients (mostly non-immune) with acute, uncomplicated Plasmodium falciparum infection were randomly assigned to either CGP 56697 (n = 51) or halofantrine (n = 52). CGP 56697 proved superior with respect to parasite clearance time (median 32 vs. 48 h, P < 0.001) and parasite reduction at 24 h (median 99.7 vs. 89.6%, P < 0.001) with a non-significant difference in resolution of fever (median 24 vs. 32 h, P = 0.835). However, a 28-day cure rate of 82% was observed for CGP 56697 and 100% for halofantrine. Significant QTc prolongations (> 30 ms) were seen 6-12 h after halofantrine intake but not after CGP 56697 intake. CGP 56697 is an effective, well-tolerated treatment for uncomplicated falciparum malaria but for this dosing regimen the recrudescence rate is unacceptablyhigh (18%). For travellers contracting malaria abroad, we propose a six-dose regimen of CGP 56697 over 3 days.
van Agtmael
M
M
Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Centre, Amsterdam, The Netherlands. agtmael@bacl.azr.nl
Bouchaud
O
O
Malvy
D
D
Delmont
J
J
Danis
M
M
Barette
S
S
Gras
C
C
Bernard
J
J
Touze
J E
JE
Gathmann
I
I
Mull
R
R
D000293:Adolescent; D000328:Adult; D000349:Africa / Q000208:ethnology; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004311:Double-Blind Method; D004338:Drug Combinations; D004983:Ethanolamines; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D005602:France; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000208:ethnology / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010270:Parasite Egg Count; D010616:Phenanthrenes / Q000627:therapeutic use*; D010963:Plasmodium falciparum / Q000302:isolation & purification; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013997:Time Factors; D014195:Travel; D014329:Tropical Climate
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D010616:Phenanthrenes; D012717:Sesquiterpenes; C023768:halofantrine