Rifampicin/Cotrimoxazole/Isoniazid versus mefloquine or quinine + sulfadoxine- pyrimethamine for malaria: a randomized trial.
OBJECTIVE
Previous studies of a fixed combination including cotrimoxazole, rifampicin, and isoniazid (Cotrifazid) showed efficacy against resistant strains of Plasmodium falciparum in animal models and in small-scale human studies. We conducted a multicentric noninferiority trial to assess the safety and efficacy of Cotrifazid against drug-resistant malaria in Papua New Guinea.


METHODS
The trial design was open-label, block-randomised, comparative, and multicentric.


METHODS
The trial was conducted in four primary care health facilities, two in urban and two in rural areas of Madang and East Sepik Province, Papua New Guinea.


METHODS
Patients of all ages with recurrent uncomplicated malaria were included.


METHODS
Patients were randomly assigned to receive Cotrifazid, mefloquine, or the standard treatment of quinine with sulfadoxine-pyrimethamine (SP).


METHODS
Incidence of clinical and laboratory adverse events and rate of clinical and/or parasitological failure at day 14 were recorded.


RESULTS
The safety analysis population included 123 patients assigned to Cotrifazid, 123 to mefloquine, and 123 to quinine + SP. The Cotrifazid group experienced lower overall incidence of adverse events than the other groups. Among the efficacy analysis population (72 Cotrifazid, 71 mefloquine, and 75 quinine + SP), clinical failure rate (symptoms and parasite load) on day 14 was equivalent for the three groups (0% for Cotrifazid and mefloquine; 1% for quinine + SP), but parasitological failure rate (P. falciparum asexual blood-stage) was higher for Cotrifazid than for mefloquine or quinine + SP (9% [PCR corrected 8%] versus 0% and 3%, respectively [p = 0.02]).


CONCLUSIONS
Despite what appears to be short-term clinical equivalence, the notable parasitological failure at day 14 in both P. falciparum and P. vivax makes Cotrifazid in its current formulation and regimen a poor alternative combination therapy for malaria.
Genton
Blaise
B
Swiss Tropical Institute, Basel, Switzerland. Blaise.genton@unibas.ch
Mueller
Ivo
I
Betuela
Inoni
I
Casey
Gerard
G
Ginny
Meza
M
Alpers
Michael P
MP
Reeder
John C
JC