A Randomized Open Label Parallel Clinical Study to Evaluate the Safety and Efficacy of Clevira Syrup against Common Cold and Cough
Anoop Austin1*, Abiraamasundari2 and Esekia Raja Selvan1
1Apex laboratories private limited R&D, B/59, SIPCOT, Industrial Park, Irungattukottai, Kancheepuram District
2SpinoS Life Science and Research Private limited, Door No. 29 A, Krishna Madura Vanam, Coimbatore
*Corresponding author: Anoop Austin, Apex laboratories private limited R&D, B/59, SIPCOT, Industrial Park, Irungattukottai, Kancheepuram District- 602 117
Citation: Austin A, Abiraamasundari and Selvan RE. (2024) A Randomized Open Label Parallel Clinical Study to evaluate the Safety and Efficacy of Clevira Syrup against Common Cold and Cough. J Clin Pract Med Case Rep. 1(1):1-14.
Received: March 14, 2024 | Published: May 06, 2024.
Copyright© 2024 genesis pub by Austin A. CC BY-NC-ND 4.0 DEED. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives 4.0 International License. This allows others distribute, remix, tweak, and build upon the work, even commercially, as long as they credit the authors for the original creation.
Abstract
Objective: To compare the efficacy of Clevira Syrup in Human adult patients, with common cold and cough.
Methods: An Open Label, Balanced, Randomized, Multi-Dose, Two-Treatment, Parallel, Comparative Phase III Clinical trial to determine the safety and efficacy of Clevira syrup. 20 Patients were enrolled and received Clevira syrup along with Standard Treatment for common cold. Before enrolling in the Haematology, Biochemistry, Serology, RT-PCR and Chest X-Ray were done to the patients for Diagnostic purpose/Confirmation of infection.
Results: All the patients demonstrated safety measures with respect to Blood pressure and Pulse rate. Also, statistically significant (p<0.0001) improvement showed in temperature from baseline (101.74± 0.60) and at the end of the study treatment (97.71 ± 0.92).
Conclusion: The study demonstrated an expedited clinical cure with normal vital signs & hematological results, which validated that Clevira is safe and efficacious in patients with common cold and cough. The data further entrusted that Clevira syrup can be used in patients with common cold and cough and relieve the signs and symptoms, with a rapid recovery, without any adverse side effects.
Keywords
Bronchitis; Clevira Syrup; Common Cold; Cough; Emphysema; RT -PCR.
Introduction
Clevira is a Proprietary Ayurvedic Medicine. The individual herbal ingredients used are known to have variety of medicinal properties against fever of viral origin and proven to have effective antipyretic, analgesic, anti-viral and immune-modulatory properties [1].
Clevira Syrup, a polyherbal formulation from apex laboratories, is a combination of ten ingredients, used in traditional medicine for management of viral infection and other disease conditions. The formulation is made out of Papaya leaf (Carica papaya), Persian Neem leaf (Melia azedarach), King of bitters plant (Andrographis paniculata), Khus Khus root (Vetiveria zizanioides), Pointed Guard plant (Trichosanthes dioica), Nutgrass (Cyperus rotundus), Ginger (Zingiber officinale), Black Pepper (Piper nigrum), Carpet Weed (Mollugo cerviana) and Heart-leaved Moonseed stem (Tinospora cordifolia). These ingredients were found to have anti-inflammatory, anti-pyretic, antibacterial, anti-microbial, anti-cancer, antihelmintic, larvicidal, hepatoprotective, anti-diabetic, anti-obesity and hypolipidemic activity [2,3].
Respiratory infection pertaining to cold and cough are seasonal infections, predominant in winter season. Antibiotics are widely prescribed and drug resistance and allergy is a common clinical situation. To overcome this clinical challenge, Clevira Syrup was evaluated based upon the activity pertaining to its safety and efficacy in Viral infections [2]. With this rationale the study was conducted in Human Patients diagnosed with the above signs and symptoms. Further the outcome of the study could help in developing a new additional benefit in treating the patients, which is a common clinical situation.
Methodology
Study design
This study was an Open Label, Balanced, Randomized, Multi-Dose, Two-Treatment, Parallel, Comparative Phase III Clinical Trial to Determine the Safety and Efficacy of Clevira Syrup [2].
Ethical conduct of the study
The study was conducted as per the Ethical guidelines for biomedical research on human participants, ICMR (2017), ICH (Step 5) 'Guidance on Good Clinical Practice. The study was initiated after obtaining proper ethical committee approvals and registered in Clinical trial registry of India (CTRI/2023/02/050004).
Patient information and consent
Patients were asked to read the informed consent document which was followed by a presentation by the trained study personnel. All the queries of the patients were resolved before obtaining their consent. Copy of the informed consent documents (English and vernacular language versions) used for obtaining consent for participation in the study. Patients were under medical supervision throughout their stay in the clinical facility to ensure safety and wellbeing of the patients.
Diagnosis and main criteria for inclusion and exclusion
Patients who met all of the following criteria were considered for enrollment in the study:
Before enrolling in the study Hematology, Biochemistry, Serology, RT-PCR will be done to the patients for Diagnostic purpose/Confirmation of infection.
Inclusion criteria
Patients meeting all of the following criteria were considered for enrollment in the study:
Patients from either sex, at an age between 18-75 years, with an oral temperature of more than 38.0°C (100.4° F) without associated rash, body pain, Malaise, Lassitude, Bronchitis, Productive Cough, Cold, Running nose, Nasal Catarrh and Sneezing. Female patients, who tested negative for pregnancy (up to two weeks prior to the study).
Exclusion criteria
- Patients with Dengue hemorrhagic fever grade III and IV
- Patients with platelet count less than 80,000/micro litre.
- Pregnant or lactating women
- Patients who have received blood or blood products transfusion, during the current illness
- Patients with Thrombocytopenia purpura (ITP), Leukemia, Hemophilia
- Patients with serum ALT level 3 times higher than the upper limit of the normal range (>165 U/L) and Impaired renal function with serum creatinine> 1.5 mg/dl (males) and > 1.4 mg/dl (females).
- Patients who were hypersensitive, to any of the components of the formulation.
Primary selection of patients
The primary selection was to assess the efficacy of Clevira from day one of enrollment/treatment initiation, soon after the confirmation of illness, which is defined as time taken for clinical recovery. Patients enrolled based on chest X-ray report. Due to common cold and cough, patient pulmonary imaging interference was evaluated by radiologist and physician. Hence 20 patients were enrolled in for treatment with Clevira syrup.
Common pulmonary report finding for patients:
- Hyperinflation of the lungs
- Air trapping
- Increased lung markings
- Flattening of the diaphragm
Sample size and treatment
Totally 22 patients were screened and 20 Patients were enrolled and received Clevira Syrup along with Standard Treatment for common cold and cough, 20 patients were received the daily dose of Clevira Syrup 10 ml twice or thrice daily for 7 to 10 days based on the severity of infection.
Data Analysis
Analysis sets
The statistical evaluation was performed using Chi-square test or Fisher exact test between the treatment groups. The proportion of patients with cold and cough on Day 10 and the percentage of patients receiving rescue therapy during the treatment period were analysis by using Pearson correlation coefficient or Spearman rank correlation. Statistical analysis was performed using XLSTAT/SAS softwares.
Safety analysis
A total of 20 patients involved in this study were successfully recovered from the infections. There were no adverse events and serious adverse events reported during course of the study. The planned safety analyses consisted of descriptive summaries of the data as relevant to the scale of data, e.g., frequency and percent for recovered days, and mean changes from baseline as appropriate. The details are provided in Table 6 and 7, respectively.
Efficacy and safety assessment
Evaluation Schedule
The first visit (Visit 01) is the screening Visit, followed by the second visit (Visit 02) which is a randomization visit/Study enrollment visit (Day 00). The third visit (Visit 03) is evaluation visit on Day 01 to 10. (Visit 04) is follow up visit after One month, if required. The visit is based upon the patient’s signs and symptoms, which are reduced between the treatment days and based on the Investigator’s decision.
Results
Out of 22 patients, 2 were found to be Negative for RT- PCR, hence 20 patients were enrolled for the study. Based on RT PCR results infections with the patients has been identified. Some common symptoms were observed from the patients like cough, cold, running nose, head ache, body ache and stuffy nose etc. (Figure 1).
Figure 1: Identification of the infection by RT-PCR results.
X-Ray Findings and Observation
Emphysema was observed radiologically in 3 patients, where the inner walls of the alveolar sacs were found weaken and rupture, which resulted in larger air spaces, instead of many small ones. This reduces the surface area of the lungs and, in turn, the amount of oxygen that reaches your bloodstream. Postnasal drip is the annoying sensation of mucus dripping down your throat, making you cough and clear your throat frequently. In 9 patients had post nasal drip findings. Bronchitis, was observed in 7 patients, where cough was also associated symptom. One patient had inflammation in airways and respiratory tract infection (Table 1).
|
S.No |
Patient Enrolment Number |
Gender |
Race |
Age (years) |
Chest X-Ray |
|
|
|
1 |
S002-02-001 |
F |
Asian |
37 |
post nasal drip was found |
||
|
2 |
S002-02-002 |
M |
Asian |
35 |
post nasal drip was found |
||
|
3 |
S002-02-003 |
M |
Asian |
29 |
emphysema was found |
||
|
4 |
S002-02-004 |
F |
Asian |
20 |
post nasal drip was found |
||
|
5 |
S002-02-005 |
M |
Asian |
53 |
Bronchitis |
||
|
6 |
S002-02-006 |
F |
Asian |
32 |
post nasal drip was found |
||
|
7 |
S002-02-007 |
F |
Asian |
58 |
emphysema was found |
||
|
8 |
S002-02-008 |
F |
Asian |
45 |
Bronchitis |
||
|
9 |
S002-02-009 |
M |
Asian |
68 |
emphysema was found |
||
|
10 |
S002-02-010 |
F |
Asian |
70 |
post nasal drip was found |
||
|
11 |
S002-02-011 |
M |
Asian |
65 |
post nasal drip was found |
||
|
12 |
S002-02-012 |
F |
Asian |
41 |
Inflammation in airways |
||
|
was found |
|||||||
|
13 |
S002-02-013 |
F |
Asian |
58 |
Bronchitis |
||
|
14 |
S002-02-014 |
F |
Asian |
33 |
Bronchitis |
||
|
15 |
S002-02-015 |
F |
Asian |
61 |
Bronchitis |
||
|
16 |
S002-02-016 |
M |
Asian |
23 |
Bronchitis |
||
|
17 |
S002-02-017 |
M |
Asian |
30 |
Bronchitis |
||
|
18 |
S002-02-018 |
F |
Asian |
24 |
post nasal drip was found |
||
|
19 |
S002-02-019 |
F |
Asian |
29 |
post nasal drip was found |
||
|
20 |
S002-02-020 |
F |
Asian |
36 |
post nasal drip was found |
Table 1: Chest X-ray reports for patients.
Demographic and other baseline characteristics
A total of 20 patients were enrolled into the study and their mean age, height, weight and BMI were recorded (Table 2).
|
S.No |
Patient Enrolment Number |
Gender |
Race |
Age (years) |
Height (cm) |
Weight (Kg) |
BMI (Kg/m2) |
|---|---|---|---|---|---|---|---|
|
1 |
S002-02-001 |
F |
Asian |
37 |
159.0 |
60.0 |
23.7 |
|
2 |
S002-02-002 |
M |
Asian |
35 |
166.0 |
63.0 |
22.8 |
|
3 |
S002-02-003 |
M |
Asian |
29 |
162.0 |
58.0 |
22.1 |
|
4 |
S002-02-004 |
F |
Asian |
20 |
153.9 |
52.1 |
21.9 |
|
5 |
S002-02-005 |
M |
Asian |
53 |
159.0 |
61.0 |
24.1 |
|
6 |
S002-02-006 |
F |
Asian |
32 |
156.0 |
55.0 |
22.6 |
|
7 |
S002-02-007 |
F |
Asian |
58 |
153.0 |
55.0 |
23.4 |
|
8 |
S002-02-008 |
F |
Asian |
45 |
150.0 |
53.0 |
23.5 |
|
9 |
S002-02-009 |
M |
Asian |
68 |
160.0 |
63.0 |
24.6 |
|
10 |
S002-02-010 |
F |
Asian |
70 |
159.0 |
60.0 |
23.7 |
|
11 |
S002-02-011 |
M |
Asian |
65 |
159.0 |
58.0 |
22.9 |
|
12 |
S002-02-012 |
F |
Asian |
41 |
154.0 |
56.0 |
23.6 |
|
13 |
S002-02-013 |
F |
Asian |
58 |
158.0 |
60.0 |
24.0 |
|
14 |
S002-02-014 |
F |
Asian |
33 |
155.0 |
57.0 |
23.7 |
|
15 |
S002-02-015 |
F |
Asian |
61 |
151.0 |
54.0 |
23.6 |
|
16 |
S002-02-016 |
M |
Asian |
23 |
161.0 |
62.0 |
23.9 |
|
17 |
S002-02-017 |
M |
Asian |
30 |
165.0 |
64.0 |
23.5 |
|
18 |
S002-02-018 |
F |
Asian |
24 |
156.0 |
59.0 |
24.2 |
|
19 |
S002-02-019 |
F |
Asian |
29 |
159.0 |
62.0 |
24.5 |
|
20 |
S002-02-020 |
F |
Asian |
36 |
157.0 |
59.0 |
23.9 |
All patients included in the study were Asians. Table 3 explains the summarized demographic details of patients who were enrolled in the study.
|
Parameter |
Mean |
SD |
Min |
Max |
CV% |
|
Age (years) |
42.35 |
16.11 |
20.00 |
70.00 |
38.05 |
|
Height (cm) |
157.65 |
4.19 |
150.00 |
166.00 |
2.66 |
|
Weight (kg) |
58.56 |
3.51 |
52.10 |
64.00 |
5.99 |
|
BMI (kg/m2) |
23.51 |
0.72 |
21.90 |
24.60 |
3.08 |
Table 3: Summarized Demographic details.
Efficacy Evaluation
Statistical analysis of Phase III Clinical trial of Clevira syrup
Primary and secondary end point efficacy evaluations were performed for Clevira Syrup. Primary and secondary end point of recovery analysis data from Day 1 to Day10 and safety measure analysis data for the all the patients (Demographic data, Haematology and vital signs) were performed by SAS software.
Demographic data
There is no statistically significant (p = 0.2424) difference was observed between Clevira Syrup (42.35 ± 16.11) of age and BMI (23.51 ± 16.11) (Table 4,5).
Table 4: Mean Age and BMI Average.
|
Source |
DF |
Anova SS |
Mean Square |
F Value |
Pr> F |
|
Treatment (Clevira Syrup) |
1 |
1.60000000 |
1.60000000 |
1.41 |
0.2424 |
Hematology parameters
All hematology parameters were found to be normal and within limits, and at the end of the study period of day 10 (Table 6,7).
|
Patient Enrolment Number |
Time of evaluation |
Haematology |
||||||||
|
RBC count (x1012/ µL) |
Packed Cell Volume (%) |
Total WB C count (/ µl) |
Lymphocytes (%) |
Neutrophils (%) |
Eosinophils (%) |
Monocyte (%) |
Basophils (%) |
Platelet count (× 10^9 / L) |
||
|
S002-02-001 |
Day 00 |
4.1 |
37.2 |
7412 |
46 |
49 |
2 |
2 |
1 |
181.2 |
|
Day 10 |
4.3 |
38.1 |
5330 |
38 |
59 |
0 |
2 |
1 |
190 |
|
|
S002-02-002 |
Day 00 |
4.3 |
41.4 |
7520 |
46 |
48 |
1 |
4 |
1 |
184 |
|
Day 10 |
4.4 |
42.9 |
5743 |
34 |
61 |
0 |
4 |
1 |
185 |
|
|
S002-02-003 |
Day 00 |
4 |
42.3 |
7864 |
45 |
50 |
2 |
3 |
0 |
175 |
|
Day 10 |
4.35 |
43.4 |
5672 |
31 |
65 |
0 |
3 |
1 |
182 |
|
|
S002-02-004 |
Day 00 |
4.6 |
39.6 |
7120 |
43 |
48 |
3 |
5 |
1 |
188.9 |
|
Day 10 |
4.6 |
41.5 |
6120 |
32 |
63 |
0 |
4 |
1 |
191 |
|
|
S002-02-005 |
Day 00 |
4.2 |
42.5 |
8045 |
41 |
54 |
1 |
4 |
0 |
207 |
|
Day 10 |
4.5 |
43.3 |
6258 |
29 |
66 |
1 |
4 |
0 |
210.3 |
|
|
S002-02-006 |
Day 00 |
3.9 |
38.1 |
7680 |
40 |
52 |
2 |
6 |
0 |
182.3 |
|
Day 10 |
4.6 |
40.2 |
5632 |
33 |
61 |
1 |
5 |
0 |
180 |
|
|
S002-02-007 |
Day 00 |
4.05 |
40.9 |
8140 |
49 |
47 |
0 |
3 |
1 |
211 |
|
Day 10 |
4.45 |
41.7 |
6020 |
40 |
56 |
0 |
3 |
1 |
215.1 |
|
|
S002-02-008 |
Day 00 |
4.7 |
39.7 |
8365 |
48 |
44 |
2 |
5 |
1 |
190.2 |
|
Day 10 |
4.6 |
41.4 |
6100 |
37 |
57 |
1 |
4 |
1 |
191 |
|
|
S002-02-009 |
Day 00 |
5.1 |
42.8 |
8452 |
51 |
43 |
3 |
3 |
0 |
194.3 |
|
Day 10 |
5 |
44.7 |
6146 |
33 |
63 |
1 |
3 |
0 |
194.7 |
|
|
S002-02-010 |
Day 00 |
4.4 |
38.3 |
7968 |
53 |
42 |
0 |
3 |
2 |
213.6 |
|
Day 10 |
4.7 |
40.6 |
5972 |
32 |
64 |
0 |
3 |
1 |
215 |
|
|
S002-02-011 |
Day 00 |
4.1 |
42.5 |
7840 |
48 |
43 |
2 |
6 |
1 |
224 |
|
Day 10 |
4.3 |
42.7 |
5869 |
39 |
56 |
0 |
4 |
1 |
230.6 |
|
|
S002-02-012 |
Day 00 |
4 |
40.4 |
7600 |
52 |
41 |
3 |
4 |
0 |
196 |
|
Day 10 |
4.2 |
42 |
5460 |
33 |
62 |
1 |
4 |
0 |
201 |
|
|
S002-02-013 |
Day 00 |
4.9 |
39.7 |
8000 |
50 |
48 |
0 |
2 |
0 |
184.6 |
|
Day 10 |
4.8 |
41.3 |
6220 |
31 |
67 |
0 |
2 |
0 |
200 |
|
|
S002-02-014 |
Day 00 |
4.2 |
41.2 |
7561 |
52 |
40 |
1 |
5 |
2 |
218 |
|
Day 10 |
4.4 |
43.6 |
5766 |
36 |
58 |
1 |
3 |
2 |
223 |
|
|
S002-02-015 |
Day 00 |
3.8 |
38.8 |
6946 |
49 |
44 |
2 |
4 |
1 |
210 |
|
Day 10 |
4.7 |
40.7 |
5210 |
32 |
63 |
0 |
4 |
1 |
206.7 |
|
|
S002-02-016 |
Day 00 |
4.6 |
42.3 |
7455 |
47 |
46 |
4 |
3 |
0 |
207 |
|
Day 10 |
5.1 |
44.6 |
5478 |
33 |
63 |
0 |
3 |
1 |
210 |
|
|
S002-02-017 |
Day 00 |
4.4 |
42 |
7800 |
48 |
47 |
2 |
2 |
1 |
193.4 |
|
Day 10 |
4.8 |
43.8 |
5590 |
39 |
58 |
0 |
2 |
1 |
195 |
|
|
S002-02-018 |
Day 00 |
4.5 |
40.6 |
7645 |
51 |
42 |
3 |
4 |
0 |
198.4 |
|
Day 10 |
4.9 |
42.1 |
5020 |
37 |
59 |
0 |
3 |
1 |
203.7 |
|
|
S002-02-019 |
Day 00 |
4.8 |
39.4 |
7459 |
55 |
37 |
4 |
4 |
0 |
196 |
|
Day 10 |
5.3 |
41.9 |
5349 |
35 |
60 |
1 |
4 |
0 |
194.2 |
|
|
S002-02-020 |
Day 00 |
4.2 |
38.7 |
7400 |
54 |
42 |
1 |
3 |
0 |
209 |
|
Day 10 |
4.6 |
40.5 |
5275 |
30 |
66 |
0 |
3 |
1 |
207 |
|
Table 6: Comparison of Hematology parameter between baseline and end line (Day 0 Vs Day 10).
Vital signs
During the course of study at Day 01 and Day 10, blood pressure, radial pulse rate, temperature and wellbeing status was enquired and recorded (Table 7). Paired sample t-test example baseline vs end of treatment comparison are dealt in (Table 8).
|
|
Patient Enrollment Number |
Treatment Group No.02 |
Day 0 |
Day 10 |
||||
|
Blood pressure (mm Hg) |
Radial pulse rate (Per min) |
Body temperature (°F) |
Blood pressure (mm Hg) |
Radial pulse rate (Per min) |
Body temperature (°F) |
|||
|
01. |
S002-02-001 |
Common cold & cough |
118/82 |
80 |
101.48 |
112/78 |
77 |
96.98 |
|
02. |
S002-02-002 |
Common cold & cough |
120/77 |
76 |
101.66 |
123/82 |
81 |
98.96 |
|
03. |
S002-02-003 |
Common cold & cough |
124/78 |
73 |
102.38 |
121/82 |
70 |
96.98 |
|
04. |
S002-02-004 |
Common cold & cough |
116/83 |
70 |
101.3 |
118/80 |
74 |
96.62 |
|
05. |
S002-02-005 |
Common cold & cough |
121/84 |
79 |
102.2 |
125/81 |
83 |
97.52 |
|
06. |
S002-02-006 |
Common cold & cough |
125/81 |
77 |
100.76 |
119/78 |
81 |
98.96 |
|
07. |
S002-02-007 |
Common cold & cough |
127/79 |
82 |
101.12 |
125/80 |
80 |
98.24 |
|
08. |
S002-02-008 |
Common cold & cough |
122/86 |
85 |
101.66 |
124/81 |
81 |
97.7 |
|
09. |
S002-02-009 |
Common cold & cough |
130/78 |
77 |
102.56 |
127/83 |
79 |
98.42 |
|
10. |
S002-02-010 |
Common cold & cough |
116/84 |
84 |
102.38 |
123/82 |
80 |
96.26 |
|
11. |
S002-02-011 |
Common cold & cough |
124/85 |
87 |
101.84 |
119/77 |
83 |
98.96 |
|
12. |
S002-02-012 |
Common cold & cough |
131/78 |
82 |
102.2 |
127/76 |
79 |
96.8 |
|
13. |
S002-02-013 |
Common cold & cough |
126/85 |
78 |
101.3 |
128/80 |
81 |
97.7 |
|
14. |
S002-02-014 |
Common cold & cough |
130/80 |
76 |
102.92 |
125/76 |
78 |
97.52 |
|
15. |
S002-02-015 |
Common cold & cough |
124/87 |
80 |
101.3 |
123/86 |
84 |
98.06 |
|
16. |
S002-02-016 |
Common cold & cough |
128/79 |
71 |
100.94 |
125/82 |
76 |
98.78 |
|
17. |
S002-02-017 |
Common cold & cough |
131/76 |
73 |
101.48 |
128/79 |
78 |
97.34 |
|
18. |
S002-02-018 |
Common cold & cough |
124/75 |
81 |
101.84 |
126/81 |
84 |
96.26 |
|
19. |
S002-02-019 |
Common cold & cough |
119/86 |
77 |
102.38 |
122/83 |
80 |
97.16 |
|
20. |
S002-02-020 |
Common cold & cough |
127/76 |
82 |
101.12 |
130/80 |
76 |
98.96 |
Table 7: Vital signs (Blood pressure, Radial pulse rate, Temperature Day 0 vs Day 10).
|
Difference |
DF |
t Value |
Pr> |t| |
|
Systolic Blood pressure |
19 |
0.76 |
0.4571 |
|
Diastolic Blood pressure |
19 |
0.65 |
0.5216 |
|
Pulse Rate |
19 |
-0.88 |
0.3913 |
|
Temperature |
19 |
13.87 |
<.0001 |
Table 8: Paired t-test (Baseline vs End of treatment comparison).
Patients in treatment with Clevira Syrup clearly illustrated the safety aspects with respect to Blood pressure and Pulse rate. Also, statistically significant (p<0.0001) improvement showed in temperature from baseline (101.74 ± 0.60) to end of the study treatment (97.71 ± 0.92) (Figure 2).
Figure 2: Comparison of fever scale between baseline and end line (Day 1 vs Day 10).
Recovery Analysis
Mean recovery day (Mean ± SD) of Treatment (Clevira Syrup were found to be 7.90 ± 1.21) (Table - 9). The Overall Clinical efficacy shows healthy recovery rate found from 20 patients.
| Treatment | N | Mean | Std Dev | Minimum | Maximum | Coeff of |
| Obs | Variation | |||||
| Clevira Syrup- Day 10 | 20 | 7.9 | 1.21 | 6 | 10 | 15.31 |
Table 9: Analysis Variable: Recovery Day.
Discussion
The main objectives of this study was to compare the efficacy of Clevira Syrup with Standard Supportive Care Treatment in Human Adult Patients with common cold and cough that affects nose, throat, and sometimes the lungs and monitor the safety and tolerability of Clevira in patient. There was a significant improvement in the quality of life of subjects in Clevira syrup related to the signs and symptoms of fever, sneezing, cough, headache, sore throat, runny nose, trouble in swallowing, compared to that of baseline.
From the study results of treatment with Clevira syrup, it is evident that the normalization of body temperature, cold symptoms, decrease in cough and infectious symptoms were down to significant levels in the treated Clevira syrup group from Day 1 to Day 10. This effect is probably due to the presence of antiviral property of A. paniculata, C. papaya, T. cordifolia and T. dioica which are the active ingredients of Clevira and it is proactive process of inhibit the viral growth [4,5]. It is clear that rapid recovery observed on Day 7 onwards in Clevira syrup group patients and herbal ingredients can boost to block [6,7] the spread of virus and prevent initial replication cycles [8] due to presence of M. azedarach [9] in Clevira. Thus, our present studies demonstrated that, Clevira is having a good anti-allergic activity [10]. It is also evident that Clevira is having a significant improvement from common cold and cough from Day 7 to Day 10 and it elucidated best recovered at end of the study Day 10 for 20 patients.
There was a significant improvement in the quality of life of subjects in Clevira group related to the fatigue, sense of feeling week, dizziness and sense of feeling depressed, compared to that of baseline and control group [11]. The overall response of Clevira group showed remarkable improvement [12] and were completely free from viral symptoms and very good subject compliance was also observed. There were no clinically significant adverse events during the entire study period [1].
Clevira, with its polyherbal ingredients showed a significant antiviral action against coronavirus, when given in addition to the standard of care medications suggested by Indian Council of Medical Research (ICMR), which is also an recommended formulation for mild to moderate COVID-19 patients [1].
The antiviral property is also elucidated by the presence of 52 major phyto-constituents [2], which was identified by in silico studies, further substantiating its antiviral properties. From the Clinical study, it is clearly evaluated that all the hematological parameters were found to be normal and within normal limits at the end of the study period (Day 10) and all patients in treatment with Clevira Syrup (N = 20) showed no side effects and safety issues with respect to the parameters tested in this study.
Hence, this Phase III clinical study clearly demonstrates its clinical cure and normal vital signs & hematological results, to understand that Clevira Syrup is safe and efficacious in patients with Common cold signs and symptoms of the viral infection and for a rapid recovery without any adverse effects.
Conclusion
The Overall Clinical efficacy clearly demonstrates it good recovery percentage, which was observed among the infected patients for treatment with Clevira Syrup. Moreover, Clevira Syrup demonstrated, expedited cure, clinically on Day 7 to 10, showing the marked improvement of cure status, from the clinical signs and symptoms.
This randomized, Phase III clinical study has shown that Clevira is as clinically effective and safe as Contagious Respiratory Illness by Viruses causing cold and cough that infect the nose, throat, and respiratory track.
Conflict of Interest
There is no conflict of Interest.
Acknowledgements
The authors are thankful to the management of apex laboratories private limited and Mr. S.S. Vanagamudi, Chairman & Managing Director, Mr. Vishagan Sulur Vanagamudi, Director & President and Ms. Subashini Vanagamudi,Executive Director, for their continuous encouragement and support in carrying out the study.
References
- Narayanababu R, Ramesh Kannan S, Lenin R, Sakthibalan M, Sudha KM, et al. (2022) Evaluation of Efficacy and Safety of Clevira as an Add on Drug in Mild to Moderate COVID-19 Positive Patients: A Randomized Control Trial. J Clin Diag Res. 16(2):1-7.
- Kannan SR, Sivraman V, Muralikumar VR, Sakthibalan M, Jayashree S, et al. (2019) A Randomized Open Label Parallel Group Clinical Study to Evaluate the Efficacy and Safety of Clevira in Fever of Viral Origin, Int J Innovative Res Med Sci. 4(9):556-66.
- Uma Narayanamurthy, Mirunalini R, Subha V, Manimekalai K, Sakthibalan K, et al. (2021) Acute and Repeated Dose Toxicity Study of Clevira Syrup – A Polyherbal Formulation, Biomed Pharmacol J. 14(3):1459-67.
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- Ansari MR. (2016) Extract of Carica papaya L. leaves: Standardizing its use in dengue fever, Indian J Pharmacol. 48(3):338-39.
- Ali-Seyed Mohamed and Kavitha Vijayaraghavan, (2020). Dengue virus infections and anti-dengue virus activities of Andrographis paniculata, Review Article, Asian Pacific J Trop Med. 13(2):49-55.
- Alché LE, Ferek GA, Meo M, Coto CE and Marta S Maier. (2003) An Antiviral Meliacarpin from leaves of Melia azedarach L. Z Naturforsch C J Biosci. 58(3-4):215-19.
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