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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
Kshirsagar M, et al.
Meta-analysis of Efficacy and Safety Studies of Septilin Tablets
Adverse effects
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 follow a
reasonable temporal sequence from
the administration of the drug;
“possible,” follows a known response
pattern to the suspected drug, but
could have been produced by the
patient’s clinical state or other modes
of therapy administered to the patient;
“probable,” follows a known response
pattern to the suspected drug that
could not be reasonably explained
by the known characteristics of the
patient’s clinical state; and “certain,”
the adverse events must have definitive
relationship to the study drug, which
cannot be explained by concurrent
disease or any other agent.
Statistical analysis
Statistical analysis was done according
to the intention-to-treat principles.
Changes in various parameters from
baseline values and values at the end
of the study were pooled and analyzed
cumulatively using Chi square test
or paired
t
test. Values are expressed
as mean ± SD or as incidences of
patients with or without symptoms.
The minimum level of significance
was fixed at 95% confidence limit and
a two-sided
P
≤ .05 was considered
significant. Statistical analysis was
performed using GraphPad Prism
version 4.03 for Windows (San Diego,
CA, USA).
Results
The break-ups for upper and lower
RTIs are given in Table 1. Statistically
significant improvement was seen in
trials conducted in patients with RTI.
Table 1. Break-up of Patients With RTI
(n = 2765)
Indication No. of
Patients
Indication No. of
Patients
Upper RTI
Lower RTI
Tonsillitis
565 Persistent
cough
(COPD)
155
Pharyngitis 599 Bronchitis 683
Laryngitis
25
Sinusitis
424
Rhinitis
278
COPD, chronic obstructive pulmonary
disease; RTI, respiratory tract infection.
Table 2. Meta-analysis of Efficacy Studies on
Septilin in RTI (32 open trials + 1 placebo
controlled trial + 5 comparative controlled
trial = 38 clinical trials)
Indication
No. of
Patients
Improvement
%
Pro-
tection
RTIs
2765 2178
a
78.77
Upper RTI
1613
1211
a
75.08
Tonsillitis
565
460
a
81.42
Pharyngitis 599
411
a
68.61
Laryngitis
25
24
a
96.00
Sinusitis
424
326
a
76.89
Rhinitis
278
253
a
91.01
Lower RTI
838
720
a
85.92
Persistent
Cough
(COPD)
155
131
a
84.52
Bronchitis
683
589
a
86.24
COPD, chronic obstructive pulmonary
disease; RTI, respiratory tract infection.
a
P
< .0001 compared to the total number
of patients with RTI before treatment.
Of the 1613 patients with URTI, 1211
patients responded to the treatment,
with a statistical significance of
P
< .0001 and percent protection of
75.08% and among the 838 patients
with lower RTI (LRTI), 720 patients
responded to the treatment, with a
statistical significance of
P
< .0001
and percent protection of 85.92%
(Table 3). Among the patients with
URTI, in 565 patients of tonsillitis,
460 patients responded with 81.42%
protection; in 599 pharyngitis
patients, 411 responded showing
68.61% protection; in 25 patients with
laryngitis, 24 showed 96% protection
in patients with sinusitis and rhinitis,
76.89% and 91.01% protection was
observed, respectively (Table 2).
Similarly in LRTI out of 683 patients
with bronchitis, 589 responded with
86.24% and persistent cough due to
varied etiology there was 84.52% relief
(Table 2). In the comparative control
trial, 74.42% of patients treated with
Septilin improved as compared to the
control group (52.86%) treated with
anti-allergics and antibiotics. The
statistical significance was
P
< .0001
(Table 3) in both Septilin and control
groups, but improvement was found
to be better with Septilin treatment.
The comparative drugs were anti-
allergics (chlorpheniramine maleate)
and antibiotics (cotrimoxazole and
penicillin). The immunoglobulin levels
showed significant improvement, IgG
from 1456.00 ± 342.80 mg/dL at
baseline to 1715.00 ± 287.10 mg/ dL
after the treatment (
P
< .009), IgA
from 200.80 ± 46.73 mg/dL before the
treatment to 241.40 ± 43.26 mg/ dL
after the treatment (
P
< .01), and IgM
levels from 167.80 ± 68.38 mg/ dL
before the treatment to 195.70 ± 63.21
mg/dL after the treatment (
P
< .01),
in 2 open-label clinical trials (Table
4). These observations support the
immunomodulatory effect of Septilin.
Out of the 2765 patients with RTI,
in patients treated with Septilin,
gastrointestinal disturbances in 11
cases (0.39%), dry mouth in 9 cases
(0.32%), and skin rashes in 3 patients
(0.11%) were observed. In patients
treated with comparative controlled
drugs (antibiotics and anti-allergics)
patients presented with adverse effects
such as drowsiness and sedation in 21
cases (18%), dry mouth in 7 patients
(7.78%), and dizziness and improper
coordination of movements in 3 cases
(3.33%).
All adverse effects were mild in nature
and did not necessitate withdrawal of
study medication (Table 5). Majority
of the adverse effects were seen in
patients treated with comparative
