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

2005 IDN; Yeka 2007 UGA; Zongo 2007 BFA). Laboratory staff
were blinded to treatment allocation in five out of six trials.
Total failure
PCR adjusted treatment failure with DHA-P was below 5% in
four out of six studies and with AL6 in two out of six studies.
Of note, one trial from Africa (Kamya 2006 UGA) found PCR
adjusted failure to be > 10% with both combinations.
In trials from Africa DHA-P performed significantly better than
AL6 at day 42 (three trials, 1136 participants: PCR unadjusted
Heterogeneity: Chi² P < 0.0001, I² = 91%, Analysis 2.1; PCR
adjusted RR 0.39, 95% CI 0.24 to 0.64, Analysis 2.2). Although
there is substantial heterogeneity among PCR unadjusted results
the direction of effect is consistently in favour of DHA-P.
In the one trial from Asia both drugs performed well with a non
significant trend towards reduced re-infections with DHA-P (one
trial, 356 participants, Analysis 2.1; Analysis 2.2; Analysis 2.3;
Analysis 2.4).
In Oceania Karunajeewa 2007 PNG showed a reduction in PCR
adjusted treatment failure at day 28 with AL6 but this effect was no
longer significant at day 42 (one trial, 356 participants, Analysis
2.1; Analysis 2.2; Analysis 2.3; Analysis 2.4).
P. vivax
Participants treated with DHA-P had significantly fewer episodes
of P. vivax parasitaemia during 42 days follow up (four trials, 1442
participants: RR 0.32, 95% CI 0.24 to 0.43, Analysis 2.5). Of
these four trials only one (Ratcliff 2005 IDN) included participants
with P. vivax co-infection at baseline.
Gametocytes
Four trials reported the development of gametocytes in those negative
at baseline and the results were highly heterogenous and could
not be pooled (four trials, 1203 participants, heterogeneity: Chi²
P = 0.006, I² = 76%, Analysis 2.6). This heterogeneity is consistent
with the performance of the two drugs for total failure. In
the two trials from Uganda (Kamya 2006 UGA and Yeka 2007
UGA) DHA-P had significantly fewer treatment failures and was
also significantly better at reducing gametocyte development. In
trials with no difference for treatment failure (Zongo 2007 BFA
and Mens 2007 KEN) there was also no difference in gametocyte
development. Karunajeewa 2007 PNG and Ratcliff 2005 IDN
report no differences in gametocyte carriage between groups but
did not give figures.
Anaemia
Four trials report changes in haemoglobin from baseline to the
last day of follow up (day 28 or 42). There is a non significant
trend towards a benefit with DHA-P but this is unlikely to be of
clinical significance (four trials, 1356 participants, Analysis 2.7).
In addition Karunajeewa 2007 PNG reports that haemoglobin
remained similar in all groups (no figures given).
Adverse events
No significant difference has been shown in the frequency of serious
adverse events (five trials, 2110 participants, Analysis 2.8).
Kamya 2006 UGA and Karunajeewa 2007 PNG report no differences
between groups (two trials, 671 participants). Ratcliff 2005
IDN reports more diarrhoea (P = 0.003) with DHA-P (774 participants).
Mens 2007 KEN reports more weakness (P = 0.035)
with AL6 (146 participants). Yeka 2007 UGA reports more abdominal
pain (P = 0.05) with AL6 (414 participants). Zongo 2007
BFA reports more abdominal pain (P < 0.05) and headache (P
< 0.05) with AL6 (375 participants). For a summary of adverse
event findings see Appendix 4.
Early vomiting
No difference has been shown in the frequency of drug related
vomiting (two trials,1147 participants, Analysis 2.9).
Comparison 3. DHA-P versus artesunate plus amodiaquine
We found two trials (one in Africa and one in Asia) which assessed
this comparison. Allocation concealment was assessed as low risk
of bias in one trial (Hasugian 2005 IDN) and unclear in the other.
In both trials laboratory staff were blinded to treatment allocation,
but other staff and participants were unblinded.
Total failure
PCR adjusted treatment failure with DHA-P was below 5% in
both trials, and below 10% with AS+AQ.
DHA-P performed significantly better than AS+AQ at day 28 (two
trials, 679 participants: PCR unadjusted RR 0.53, 95% CI 0.35
to 0.81, Analysis 3.1; PCR adjusted RR 0.47, 95% CI 0.23 to
0.94, Analysis 3.2). The one trial that reports outcomes at day 42
(Hasugian 2005 IDN) had high losses to follow up (> 20%) at
this time point (Analysis 3.3; Analysis 3.4).
P. vivax
Hasugian 2005 IDN reports significantly fewer episodes of P. vivax
parasitaemia with DHA-P by day 42 (one trial, 170 participants:
RR 0.25, 95% CI 0.09 to 0.74, Analysis 3.5).
Gametocytes
Artemisinin-based combination therapy for treating uncomplicated malaria (Review)
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Both trials report no significant differences in gametocyte carriage
during follow up (figures not reported).
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