Topical treatments for fungal infections of the skin and nails of the foot.

(i) Placebo controlled trials
Allylamines Versus Placebo
Two different allylamines (naftifine 1% and terbinafine 1%) used
for 1 to 4 weeks were evaluated in 11 placebo controlled randomised
trials.
Short-term outcome (two weeks)
Naftifine
Short-term outcomes were available for all 5 trials using naftifine
(n = 612) Klaschka 1984; Dobson 1989; Schachner 1990; Bagatell
1991a; Bagatell 1991b. Overall the observed relative reduction
in risk of treatment failure was 25% (RR 0.75, 95% CI 0.60 to
0.93; Analysis 1.1), although there was substantial variation in the
individual study results (I 2 = 79%).
Terbinafine
For terbinafine, short-term outcomes were available for 4 trials (n
= 316, Berman 1992; Evans 1991; Korting 1997; Syed 2000). The
results were inconsistent between studies, giving an overall relative
reduction in treatment failure of 42% which was not statistically
significant (RR 0.58, 95% CI 0.31 to 1.08; Analysis 1.1).
Across all 9 trials providing short-term outcome of 1% allylamines
for a period of 1 to 2 weeks compared with placebo, there was a
pooled relative reduction in treatment failure at 2 weeks of 31%
(RR 0.69, 95% CI 0.56 to 0.87; Analysis 1.1), with substantial
variation in individual study results (I 2 = 79%).
Medium-term outcome (six weeks)
Naftifine
Topical treatments for fungal infections of the skin and nails of the foot. (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Naftifine (1%) used for 4 weeks was evaluated in 5 trials (n = 607,
Bagatell 1991a; Bagatell 1991b; Dobson 1989; Klaschka 1984;
Schachner 1990), a 58% relative reduction in treatment failure was
observed (RR 0.42 95% CI 0.30 to 0.59; Analysis 1.2, Naftifine (tx
4 weeks) versus Placebo), with substantial variation in individual
study results (I 2 = 68%).
Terbinafine
Terbinafine (1%) was used for 1 week (2 trials, n = 229, Berman
1992; Korting 2001), 2 weeks (2 trials, n = 240, Evans 1991;
Savin 1994) and 4 weeks (2 trials, n = 40, Savin 1990; Smith
1990a). A statistically significant reduction in risk of treatment
failure was observed with each treatment duration (RR 0.16, 0.36,
0.18 respectively; Analysis 1.2). Pooling across all durations, a 77%
relative reduction in treatment failure was observed (RR 0.23,
95% CI 0.15 to 0.38, pooled result not shown in the Forest plots
(MetaView), with moderate variation in individual study results
(I 2 = 50%).
A meta-analysis of data from all 11 trials (n = 1116) comparing 1%
allylamines with placebo (treatment for a period of 1 to 4 weeks)
provided an estimated relative reduction in the risk of treatment
failure of 67% (RR 0.33, 95% CI 0.24 to 0.44; Analysis 1.2), with
substantial variation in individual study results (I 2 = 67%). All
of the results were based on at least 80% follow up except those
from the trials evaluating terbinafine used for 2 weeks. A sensitivity
analysis based on the exclusion of data collected in these two trials
(Evans 1991; Savin 1994) showed a similar overall estimate of
effectiveness (RR of treatment failure 0.31, 95% CI 0.21 to 0.45;
Analysis 1.3). The variation in individual study results remained
substantial (I 2 = 75%).
A L’Abbé plot of the outcomes at 6 weeks (Figure 1) demonstrates
that the allylamines generally had treatment failure rates of around
30%, compared to around 85% for placebos, though there was
considerable variation in individual trial results (see MeMethods,
Assessment of heterogeneity for more details of L’Abbé plots and
how to interpret them) .
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