Artesunate Plus Sulfadoxine-Pyrimethamine Versus Chloroquine for Vivax Malaria
Information source: London School of Hygiene and Tropical Medicine
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Malaria, Vivax
Intervention: Sulfadoxine-pyrimethamine + artesunate (Drug); Chloroquine (Drug)
Phase: Phase 2
Sponsored by: London School of Hygiene and Tropical Medicine
Official(s) and/or principal investigator(s):
Mark W Rowland, PhD, Principal Investigator, Affiliation: London School of Hygiene and Tropical Medicine
The purpose of this study was to determine whether the proposed first line treatment for
falciparum malaria in this region (sulfadoxine-pyrimethamine + artesunate) would be no worse
a treatment for vivax malaria that the standard vivax treatment of chloroquine. In areas
where vivax and falciparum malaria co-exist misdiagnosis of vivax malaria as falciparum is
not unlikely; it is important to know whether adequate treatment will be received in these
Official title: A Randomised Non-Inferiority Trial of Sulfadoxine-Pyrimethamine Plus Artesunate Compared to Chloroquine for the Treatment of Vivax Malaria in Eastern Afghanistan.
Study design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Efficacy Study
Primary outcome: Proportion of patients with parasitological cure up to day 28 after treatment (defined as clearance of circulating vivax parasites by day 7 and absence until end of follow-up).
Secondary outcome: Parasite and fever clearance times, the proportion of patients free of parasites at 42 days, and the proportion of patients with detectable gametocytes during follow-up.
In areas co-endemic for falciparum and vivax malaria incorrect differential diagnosis is
always a risk. Where the recommended treatment for the two diseases is the same this presents
no problem for effective treatment or clinical cure of either species. Chloroquine remains an
effective treatment of choice for vivax malaria in most settings, but with the spread of
chloroquine-resistant falciparum malaria across Asia, many countries now use
artemisinin-based combination therapy for this species of malaria. Differential diagnostic
practices, have not improved in parallel. In Afghanistan the adoption of
sulfadoxine-pyrimethamine plus artesunate (SP+AS) as first-line falciparum treatment raises
the prospect of a significant proportion of vivax malaria being misdiagnosed and treated with
the combination. SP is considered to have limited efficacy against vivax malaria and the
efficacy of SP+AS against vivax has not been established in areas that have made the switch.
A randomized, non-inferiority trial comparing SP+AS (1 day SP, 3 days AS) to chloroquine
monotherapy was undertaken on 190 vivax patients in Eastern Afghanistan. A margin of
equivalence of 14%, with 90% power and 95% CI (two-sided α = 0. 05) was used. Standard WHO
procedures for in vivo evaluation of antimalarial drugs were followed. 180 individuals
completed the trial to day 42. The primary outcome was proportion of patients free from
failure at day 28. Using a per protocol analysis both regimens resulted in ≥96% treatment
success at 28 days, but significantly more cases failed in the CQ arm (46%) than in the SP+AS
arm (24%) by day 42. Based on predetermined statistical criteria SP+AS was shown to be
non-inferior to the standard chloroquine treatment. In areas where vivax infections might be
misdiagnosed as falciparum infections and treated with SP+AS, patient management would be as
good or better than with the standard CQ treatment.
Minimum age: 2 Years.
Maximum age: N/A.
- microscopy confirmed P. vivax mono-infection
- age >2 years
- weight >5kg
- >1 asexual parasite per 10 fields
- evidence of concomitant infection or serious disease
- recent use of antimalarial drugs
- severe malaria
- known allergy to study drugs
Locations and Contacts
Starting date: March 2004
Ending date: August 2004
Last updated: June 13, 2007