Artemisinin-based combination therapy for ... - The Cochrane Library

The six-dose regimen of AL6 has been shown to be superior to
the four-dose regimen (Vugt 1999; Omari 2006). In this review
we have only included the six-dose regimen.
Comparison 9. AL6 versus artesunate plus amodiaquine
We found twelve trials (all in Africa) which assessed this comparison.
Three of these trials were excluded after sensitivity analysis
due to baseline differences which had the potential to bias
the result in favour of AL6 (Analysis 9.9; Analysis 9.10). Of the
remaining nine trials allocation concealment was assessed as low
risk of bias in five trials (Adjei 2006 GHA; Bukirwa 2005 UGA;
Dorsey 2006 UGA; Kobbe 2007 GHA; Mutabingwa 2004 TZA)
and laboratory staff were blinded to treatment allocation in four
trials.
Total failure
PCR adjusted treatment failure was below 5% for both AL6 and
AS+AQ in six out of eight trials. In two more recent trials (both
from Ghana), PCR adjusted treatment failure for both arms was
above 5% and for AL6 above 10% (Analysis 9.2).
No difference has been shown in PCR adjusted total failure at
day 28, either within individual trials or after pooling (eight trials,
1729 participants, Analysis 9.2). There is substantial heterogeneity
in PCR unadjusted failure (nine trials, 3021 participants: heterogeneity
Chi² P < 0.0001, I² = 76%, Analysis 9.1). Subgroup
analysis seems to suggest regional differences, with studies from
East Africa showing benefit with AL6 and recent studies from
West Africa favouring AS+AQ (Analysis 9.1). However, substantial
heterogeneity remains, and further subgroup analysis by trial
characteristics and transmission intensity did not expand the interpretation
of this heterogeneity.
P. vivax
One trial (Dorsey 2006 UGA) reported on P. vivax but there were
too few patients to draw a conclusion (AL6: 8/202 at baseline and
3/202 during follow up, AS+AQ: No vivax at any time point).
Gametocytes
Bukirwa 2006 found that AL6 significantly reduced the development
of gametocytaemia in patients who did not have detectable
gametocytes at baseline (one trial, 305 participants: RR 0.34, 95%
CI 0.15 to 0.74, Analysis 9.3). Three trials reporting gametocyte
carriage over 14 days of follow up do not show a clear advantage
with either combination (three trials, 1078 participants, Analysis
9.4).
Anaemia
Four studies reported some measure of haematological recovery
from baseline to day 28 and did not show a difference between the
two combinations (four trials, 2356 participants, Analysis 9.5).
Guthmann 2004 AGO reported the proportion of participants
who were anaemic (Hb < 11 g/dl) at day 0 and 28 and did not
show a difference (one trial, 123 participants, Analysis 9.6). Three
trials (Dorsey 2006 UGA; Faye 2003 SEN; Mutabingwa 2004
TZA) also reported measures of anaemia at day 14 and did not
show a difference.
Adverse events
No difference has been shown in the frequency of serious adverse
events (six trials, 2749 participants, Analysis 9.7).
No important differences in adverse events were reported between
groups. For a summary of adverse events see Appendix 4.
Early vomiting
No difference has been shown in the frequency of early vomiting
(five trials, 1097 participants, Analysis 9.8).
Comparison 10. AL6 versus artesunate plus sulfadoxinepyrimethamine
We found four trials (three from Africa and one from Oceania)
which assessed this comparison. Two of these trials were excluded
from the primary analysis due to baseline differences between the
groups (Analysis 10.6; Analysis 10.7). Allocation concealment was
judged to be at high risk of bias in the two remaining trials. Laboratory
staff were blinded to treatment allocation in one trial.
Total failure
In Oceania, Karunajeewa 2007 PNG found no difference in
PCR unadjusted failure (one trial, 217 participants, Analysis 10.1;
Analysis 10.3), but did show a significant reduction in PCR adjusted
treatment failure with AL6 at both day 28 and day 42 (one
trial, 217 participants: Day 42 RR 0.33, 95% CI 0.13 to 0.86,
Analysis 10.2; Day 28 RR 0.28, 95% CI 0.08 to 0.97, Analysis
10.4). PCR adjusted treatment failure with AS+SP was > 20% at
day 42.
In Africa, Mukhtar 2005 SDN found no difference between the
two groups (one trial, 157 participants, Analysis 10.3, Analysis
10.4).
P. vivax
Artemisinin-based combination therapy for treating uncomplicated malaria (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Karunajeewa 2007 PNG found no differences in the incidence
of P. vivax parasitaemia by day 42 in participants treated for P.
falciparum mono-infection at baseline (one trial, 196 participants),
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