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Clinical insight
P R O B E
• V o l . L I I I • N o . 3 • A p r – J u n 2 0 1 4
Karamakar D, et al.
Meta-analysis of Efficacy and Safety Studies of Cystone
population outcome and intervention.
1
Meta-analysis (quantitative synthesis
or overview analysis) is a term used
to describe quantitative methods
for combining information across
different studies.
2
A meta-analysis is a 2-stage process;
the first stage is the extraction of data
from each study and the calculation of
the result for each study. The second
stage involves deciding whether it
is appropriate to calculate a pooled
average result across studies. This
process gives greater weightage to the
results from the studies that give more
information because these are likely to
be closer to the truth we are trying to
estimate.
1
Urolithiasis or renal calculi are
crystal aggregations of dissolved
materials in the urine and hence the
process is called urolithiasis. The
sequence of formation of urinary
stone involves urinary saturation,
urinary supersaturation, nucleation,
crystal growth, crystal aggregation,
and urinary stone formation. Urinary
stones are formed because of metabolic
disturbances like hypercalciuria,
hyperoxaluria, cystinuria, etc.
Sometimes, urinary stones are formed
because of chronic urinary tract
infections (UTIs). Urinary stones
can be calcium stones, cystine stones,
uric acid stones, or struvite stones.
They typically form inside the kidney
(nephrolithiasis), ureter (urolithiasis),
or urinary bladder. These calculi can
vary in size and shape and when they
grow up to 2.3 mm, they can cause
obstruction of the ureter. This may
lead to obstruction with dilation or
stretching of the upper ureter and
renal pelvis as well as spasm leading
to severe episodic abdominal pain,
which may be associated with nausea
and vomiting. At present, no medical
therapy is available for dissolution or
displacement of renal stones.
A number of herbs and their
combinations have been claimed to
have beneficial effects in urolithiasis.
Cystone is a herbomineral formulation
specifically developed for the
management of urolithiasis or renal
calculi.
This product was introduced in
Indian Medical Practice in the year
1943. Since then, more than 3200
million tablets have been sold. This
formulation is being used extensively
in the management of urolithiasis.
Till date, 80 clinical trials have been
carried out to evaluate the safety and
efficacy of Cystone in the management
of urolithiasis. The present study was
carried out to review the meta-analysis
of 50 of these clinical trials, so as to
arrive at the status of Cystone in the
management of urolithiasis.
Aim
The aim of the study was to carry out
the meta-analysis of 50 clinical trials
for identifying the efficacy and safety
of Cystone in urolithiasis.
Material andMethods
Study design
This is a cumulative meta-analysis of
50 published clinical trials of Cystone
in urolithiasis
.
Study period
This study evaluated the clinical trials
of Cystone conducted between 1954
and 2004.
Inclusion criteria
All published studies, which evaluated
the role of Cystone in urolithiasis
were included in the meta-analysis
irrespective of the study design, as
most of these researches were carried
out in India when randomized clinical
trials were not being commonly
carried out.
3-52
The meta-analysis
includes clinical trials, which were
either controlled studies or open
clinical studies. There were no
restrictions regarding sex, age, or
duration of disease. The outcome
variables included measurement data
on changes in clinical symptoms
and signs, laboratory results, and
incidence of adverse events during/
after treatment.
Exclusion criteria
Experimental phase 1 and phase 2
studies were excluded from the study
population.
Study procedure
In all, 50 clinical studies done at
various centers between 1954 and
2004 were taken into account (Table
1). From each study, the demographic
data of patients at entry was tabulated.
The duration of treatment varied from
2 weeks to 2 years and in most of the
studies, except in pediatric patients,
Cystone was used at a dosage of 2
tablets thrice daily (Table 2). Changes
in the clinical and biochemical
parameters were taken into account in
addition to the calculi size, location
of the calculi, urine volume and
urinary excretion of oxalate, uric acid,
and calcium. Studies that considered
parameters like burning micturition,
bacteriuria, and the presence or
absence of pus cells in the urine of
urolithiasis patients, were also taken
into account.
Adverse events
The incidence and type of adverse
events reported by various studies were
also tabulated separately. All adverse
events, either reported or observed
by patients, were recorded with
information about severity, duration,
and action taken regarding the study
drug. Relation of adverse events to
study medication was predefined as
“unrelated,” a reaction that does not
