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Rifampicin/Cotrimoxazole/Isoniazid versus mefloquine or quinine + sulfadoxine- pyrimethamine for malaria: a randomized trial.

Genton B, Mueller I, Betuela I, Casey G, Ginny M, Alpers MP, Reeder JC - PLoS Clin Trials (2006)

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

View Article: PubMed Central - PubMed

Affiliation: Swiss Tropical Institute, Basel, Switzerland. Blaise.genton@unibas.ch

ABSTRACT

Objectives: 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.

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

Setting: 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.

Participants: Patients of all ages with recurrent uncomplicated malaria were included.

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

Outcome measures: 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]).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Participant Flow
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pctr-0010038-g001: Participant Flow

Mentions: The safety analysis population included 137 patients in the Maprik hospital outpatient clinic, 49 in Kunjingini health subcentre, and 183 in Madang town outpatient clinic. No patient was admitted to the ward. The participant flow is detailed in Figure 1. A total of 369 patients were included, using the OptiMAL test to detect parasitaemia: 123 in the Cotrifazid group, 123 in the mefloquine group, and 123 in the quinine + SP group. Of the total in this group, 55 were excluded on day 2 since they were found not to have been treated with antimalarials in the last 28 days after reviewing their health book (nonresistant malaria). Another 64 were excluded because the microscopical investigation did not confirm the presence of asexual blood-stage parasites. The lower detection of microscopy when compared to OptiMAL is most likely due to the detection of circulating gametocytes by the rapid test, a phenomenon that was not documented when the study was designed and conducted.


Rifampicin/Cotrimoxazole/Isoniazid versus mefloquine or quinine + sulfadoxine- pyrimethamine for malaria: a randomized trial.

Genton B, Mueller I, Betuela I, Casey G, Ginny M, Alpers MP, Reeder JC - PLoS Clin Trials (2006)

Participant Flow
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1713262&req=5

pctr-0010038-g001: Participant Flow
Mentions: The safety analysis population included 137 patients in the Maprik hospital outpatient clinic, 49 in Kunjingini health subcentre, and 183 in Madang town outpatient clinic. No patient was admitted to the ward. The participant flow is detailed in Figure 1. A total of 369 patients were included, using the OptiMAL test to detect parasitaemia: 123 in the Cotrifazid group, 123 in the mefloquine group, and 123 in the quinine + SP group. Of the total in this group, 55 were excluded on day 2 since they were found not to have been treated with antimalarials in the last 28 days after reviewing their health book (nonresistant malaria). Another 64 were excluded because the microscopical investigation did not confirm the presence of asexual blood-stage parasites. The lower detection of microscopy when compared to OptiMAL is most likely due to the detection of circulating gametocytes by the rapid test, a phenomenon that was not documented when the study was designed and conducted.

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

View Article: PubMed Central - PubMed

Affiliation: Swiss Tropical Institute, Basel, Switzerland. Blaise.genton@unibas.ch

ABSTRACT

Objectives: 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.

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

Setting: 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.

Participants: Patients of all ages with recurrent uncomplicated malaria were included.

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

Outcome measures: 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]).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus