A comparative study of butoconazole, miconazole and placebo


Dyck, W.A. van, Jr

Journal of Reproductive Medicine 31(7(Supplement)): 662-663

1986


The objective of our investigation was to evaluate the safety, tolerance and effectiveness of both 1% and 2% butoconazole nitrate vaginal cream in the treatment of vulvovaginal candidiasis. The compound was applied for either three or six days, and its effects were compared to six-day treatment with 2% miconazole and with the vehicle cream as a placebo. The trial was conducted as a multicenter study using a parallel, double-blind design. Patients with clinical signs and symptoms of vulvovaginal candidiasis and who had positive wet mount preparations and cultures for Candida were enrolled. Women with trichomonads and/or clue cells in the wet smear were not eligible to participate in the study. Patients who fulfilled the protocol admission criteria were assigned to the following treatment groups: butoconazole 1% for three days followed by placebo for 3 days, butoconazole 1% for 6 days, butoconazole 2% for 3 days followed by a placebo for 3 days, butoconazole 2% for 6 days, miconazole 2% for 6 days or the vehicle for 6 days. The efficacy of the study drugs was judged by the duration of relief from the clinical signs and symptoms of vaginitis and the absence of Candida albicans, microorganisms and vaginal secretions, as established by fungal culture and potassium hydroxide preparation.

A
Comparative
Study
of
Butoconazole,
Miconazole
and
Placebo
Walter
A.
Van
Dyck,
Jr.,
M.D.
From
the
Department
of
Obstetrics
and
Gynecology,
Sunnyvale
Medical
Clinic,
Inc.,
Sunnyvale,
California.
Introduction
and
Study
Design
The
objective
of
our
investigation
was
to
evaluate
the
safety,
tolerance
and
effectiveness
of
both
1%
and
2%
butoconazole
nitrate
vaginal
cream
in
the
treat-
ment
of
vulvovaginal
candidiasis.
The
compound
was
applied
for
either
three
or
six
days,
and
its
effects
were
compared
to
six-day
treatment
with
2%
miconazole
and
with
the
vehicle
cream
as
a
placebo.
The
trial
was
conducted
as
a
multicenter
study
us-
ing
a
parallel,
double-blind
design.
Patients
with
clinical
signs
and
symptoms
of
vulvovaginal
candidi-
asis
and
who
had
positive
wet
mount
preparations
and
cultures
for
Candida
were
enrolled.
Women
with
trichomonads
and/or
clue
cells
in
the
wet
smear
were
not
eligible
to
participate
in
the
study.
Patients
who
fulfilled
the
protocol
admission
criteria
were
assigned
to
the
following
treatment
groups:
butoconazole
1%
for
three
days
followed
by
placebo
for
3
days,
butoconazole
1
%
for
6
days,
butoconazole
2%
for
3
days
followed
by
a
placebo
for
3
days,
butoconazole
2%
for
6
days,
miconazole
2%
for
6
days
or
the
vehicle
for
6
days.
The
efficacy
of
the
study
drugs
was
judged
by
the
duration
of
relief
from
the
clinical
signs
and
symp-
toms
of
vaginitis
and
the
absence
of
Candida
albicans,
microorganisms
and
vaginal
secretions,
as
established
by
fungal
culture
and
potassium
hydrox-
ide
preparation.
Results
A
total
of
695
patients
were
evaluated
for
safety.
Of
them,
568
completed
the
study
according
to
the
pro-
visions
of
the
protocol
and
were
included
in
efficacy
analyses.
Of
the
695
patients
included
in
the
safety
evalua-
tion,
2%
discontinued
treatment
because
of
side
ef-
fects.
Complaints
included
vaginal
itching
and
burn-
ing,
vulvar
swelling,
burning
on
urination
and
fre-
quency
of
urination.
Only
1
%
reported
side
effects
that
were
regarded
by
the
investigators
as
probably
related
to
the
study
drugs.
At
each
follow-up
visit,
clinical
and
microbiologic
effects
of
the
study
drug
were
evaluated
according
to
several
criteria
of
efficacy.
Clinical
cure
was
defined
as
the
absence
of
clinical
signs
and
symptoms
of
vulvovaginal
candidiasis
at
both
follow-up
examina-
tions.
Microbiologic
cure
was
defined
as
a
negative
potassium
hydroxide
preparation
and
the
absence
of
Candida
growth
on
fungal
culture
at
both
follow-up
examinations.
Therapeutic
cure
was
defined
as
both
clinical
and
microbiologic
cure
at
both
follow-up
662
Volume
31,
Number
7
(Supplement)/July
1986
663
Table
I
Cure
Rates
Treatment
group
Drug
effect
(P
value)
Placebo
1%
butoconazole
(3
days)
1%
butoconazole
(6
days)
2%
butoconazole
(3
days)
2%
butoconazole
(6
days)
2%
micanozole
(6
days)
First
follow-up
examination
Microbiologic
(536
patients)
43
85
87
85
94
84
.0001
Clinical
(545
patients)
48
76
71
81
77
75
.0004
Second
follow-up
examination
Therapeutic
(552
patients)
23
55
43
52
58
54
.0001
Microbiologic
(518
patients)
37
71
65
63
79
72
.0001
Clinical
(546
patients)
36
64
56
67
67
63
.0003
visits.
Patients
who
discontinued
therapy
at
any
time
due
to
lack
of
drug
efficacy
were
considered
treat-
ment
failures
whether
or
not
all
the
examinations
had
been
completed.
The
results
of
the
study
are
shown
in
Table
I.
Although
the
differences
between
the
butoconazole
and
miconazole
drug
groups
did
not
reach
the
level
of
statistical
significance,
the
highest
rate
of
therapeutic
cure
was
obtained
with
2%
butoconazole
for
six
days.
The
highest
microbiologic
cure
rates,
at
both
the
first
and
second
follow-up
examinations-
94%
and
79%,
respectively—were
obtained
with
2%
butoconazole
applied
for
six
days.
The
highest
clini-
cal
cure
rate
after
the
first
follow-up
examination-
81
%
—was
in
the
three-day
2%
butoconazole
group,
and
after
the
second
follow-up
examination,
both
the
three-
and
six-day
treatments
with
2%
butoconazole
showed
the
same
rate
of
clinical
cure-67%.
We
conclude
that
butoconazole
nitrate,
formulated
in
a
cream,
tested
in
1%
and
2%
concentrations
and
given
for
three
and
six
days,
is
at
least
as
active
as
six-day
treatment
with
2%
miconazole.
It
was
partic-
ularly
notable
that
in
a
subgroup
of
180
oral
contra-
ceptive
users,
the
highest
therapeutic
cure
rates
were
achieved
with
2%
butoconazole
after
three
and
six
days
(63%
and
61
%,
respectively).
Thus,
the
use
of
oral
contraceptives
did
not
negatively
affect
the
treatment
results
with
this
agent.