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A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis.

Summary

A double blind, placebo-controlled, parallel-group clinical study was carried out to evaluate the effect of an Andrographis paniculata (N.) extract SHA-10 fixed combination, Kan Jang, in the treatment of acute upper respiratory tract infections, including sinusitis. Ninety-five individuals in the treatment group and 90 individuals in the placebo group completed the study according to the protocol. The medication was taken for 5 days. Temperature, headache, muscle aches, throat symptoms, cough, nasal symptoms, general malaise and eye symptoms were taken as outcome measures with given scores. The total score analysis showed a highly significant improvement in the verum group versus the placebo. This result applied to the group as a whole and to the sinusitis subgroups. The individual symptoms of headache and nasal and throat symptoms together with general malaise showed the most significant improvement while cough and eye symptoms did not differ significantly between the groups. Temperature was moderately reduc ed in the verum group. It can be concluded that Kan Jang has a positive effect in the treatment of acute upper respiratory tract infections and also relieves the inflammatory symptoms of sinusitis. The study drug was well tolerated.

Key words: Andrographis paniculata (N.) SHA-10, Kan Jang, sinusitis, upper respiratory tract infections, double-blind study.

Introduction

A fixed combination, Kan Jang, containing a standardized extract from Andrographis paniculata SHA-10 and Eleutherococcus senticosus (R. et M.) has been used for more than 20 years in Scandinavia as a herbal medicinal product in uncomplicated upper respiratory tract infections. A number of clinical studies have been carried out, demonstrating a significant effect in the treatment of common cold. A pharmacological study has verified the rationale of the dose level used in previous studies (Caceres et al., 1997; Caceres et al., 1999; Hancke et al., 1995; Melchior et al., 1996/1997; Melchior et al., 2000). A recently performed study indicated a clear effect of the fixed combination during two influenza epidemics (Kulichenko et al., 2001).

Andrographis fixed combination and Andrographis paniculata extract have shown an immunostimulatory and anti-inflammatory action in pharmacological studies (Amroyan et al., 1999; Madav et al., 1996; Pun et al., 1993).

This clinical study was performed to investigate the effect of the Kan Jang fixed combination in a situation with less-restrictive inclusion parameters than the common cold, while excluding influenza, including more general acute upper respiratory tract infections such as sinusitis. It was decided to conduct the study at two medical centres in Yerevan, at the Department of Otolaryngology and at the Emergency Ward Department of the Erebuni Hospital. The study was performed as a double blind, placebo-controlled, non-randomized study.

The general aim of the study was to evaluate the Kan Jang fixed combination in upper respiratory tract infections, where the use of antibiotics was not immediately called for. Two special subgroups of patients with a diagnosis of sinusitis underwent a separate statistical analysis: one group with a previous history of sinusitis-like symptoms, and the other with no or few previous episodes.

Material and Methods

Study drug

The Swedish Herbal Institute, Goteborg, Sweden, in accordance with GMP, manufactured the test medication. The tablets were stored at room temperature under safe conditions. The verum and placebo were administered as 4 tablets, three times daily.

Verum: Composition containing 85 mg standardized extract of Andrographis paniculata SHA-10 equivalent to 5 mg andrographolide and 10 mg of Eleutherococcus senticosus extract equivalent to 120 mg of the crude drug.

All tablets were coated and had a similar appearance and packaging so that the placebo and drug could not be distinguished from each other. They were kept under safe conditions (in a special room) at room temperature with instructions not to be used for any other purposes than the study.

The study was performed in accordance with the revised Declaration of Helsinki (Hong Kong 1989). The protocols of the study were reviewed and approved by the Ethics Committee of Armenian Drug and Medical Technology Agency of the Ministry of Health of the Republic of Armenia.

Study design

The study was conducted as a double blind, parallel-group, placebo-controlled study with a verum group and a placebo group to investigate the efficacy and tolerability of Kan Jang in individuals with upper respiratory tract infection according to the inclusion/exclusion criteria below. The assignment of verum and placebo to the patients was done as follows: two doctors independently of each other, working at two different clinics, and with no knowledge of or contacts with each other were carrying one group each in two clinics. Thus, they did not have a possibility to exchange the information and compare results with each other. The study was carried out at the Department of Otolaryngology of Yerevan Medical State University and at the Emergency Ward Department of the Erebuni Hospital in Armenia during the period November 1997 to April 1999. The first examination was performed when the patient first visited the doctor. The second examination was performed 5 days later. Special forms were completed about case h istory and objective data. The data obtained by each doctor was analysed by the principal investigator only at the end of the study after statistical treatment of the primary information by a statistician, who did not have an information about which group took placebo or verum. In fact, it was a triple blind placebo controlled study.

Patient population

Two hundred men and women aged 15 to 64 years with a diagnosis of upper respiratory tract infection that did not require treatment with antibiotics were recruited after they had given their consent following written and verbal information about the study.

Clinical observations included an evaluation of the following signs: rhinitis, sinusitis, pharyngitis, fever, abnormal pulmonary findings and lymphadenopathy. The symptoms included nasal discharge, nasal stuffiness, sore throat, earache, cough, feverishness and headache. Signs of sinusitis (according to the classification of B.S Preibrajevski -- in practice identical to the international classification) were particularly looked for, for example unilateral pain. Patients with suspected sinusitis were distinguished from patients with, for instance rhinitis, by means of X-ray examination, ear, nose and throat (ENT) examination and fibroscopic examination.

Patients with a diagnosis of sinusitis were further divided into two groups according to data from their history:

1) patients with a history of frequent episodes of sinusitis

2) patients with no or few episodes with similar symptoms

Patient exclusion criteria

-- Temperature >39 [degrees]C

-- Patients with abnormal pulmonary findings; pleuritis, pneumonia, bronchitis

-- Patients using antibiotics and/or anti-inflammatory drugs

-- Patients with alcoholism or patients who were heavy smokers (>20 cigarettes a day)

Efficacy parameters

All efficacy parameters except the temperature were based on the patient's self-evaluation and recorded by the physician interviewing the patients. The symptoms ranged from 0 to 5 points (Figure 1).

Safety parameters

The investigating physician recorded adverse effects in the CRF. Rating of drug safety was based on physical examination, measurement of blood pressure, heart rate, laboratory examination of hematology (leukocytes, erythrocytes, hemoglobin, hematocrit, MCV, MCH), biochemistry (glucose, creatinine, gammaGT , sodium, potassium) and documentation of adverse effects. Participants were asked about any adverse effects and the answers were recorded by the clinical staff every day, after drug intake. The classification of the AEs was in accordance with EC guideline 111/3445/91-EN: mild, moderate and severe; the causality of the study medication was determined as definite, probable, possible, unlikely, not related and not possible to judge. No adverse effects were recorded during the study.

Statistical analysis

As the study was not randomized, special attention was given to the question of different initial values between the placebo group and the treatment group. On the basis of this, two different methods were used: a two-sample t test and a regression model based on expected values for visit 2 (McCall, 1990).

Two-sample t test

When applying the two-sample t test, special attention had to be paid to important differences between the groups at visit 1, namely the difference in onset of infection and the difference in mean score value.

To investigate the influence on the result, resulting from the difference in day of onset of infection, the sample was divided into three subgroups as follows.

1. group: 0 - day 1

2. group: day 2

3. group: day 3 to day 4

To investigate the influence of the difference in mean score at the start, the sample was divided similarly into three subgroups, according to the value of the mean score:

1. mean score [less than or equal to] 0.5

2. 0.5 < mean score [less than or equal to] 1.0

3. mean score > 1.0

An important question was how the difference of the individual mean score at visit 1 would influence the result. It was possible that people with a high mean score at the start would consistently improve more (or less), from visit 1 to visit 2, than those with a low mean score. To analyse the dependence of the result, both on different individual initial values, and on time of onset, as well as the interdependence between these two factors, an analysis of covariance (ANCOVA) was performed. The model is able to answer the question as to what extent the difference in improvement between the treatment group and placebo group could be attributed to the differences in the initial value and time of onset, as well as their interdependence.

Regression analysis

Since two groups A and B differ significantly with respect to initial parameter's value, the basic assumption do not validate the most commonly used statistical analysis, t-test. Nonparametric Mann Whitney test, etc. This leaves us with the choice of a statistical models based on so called regression analysis (McCall, 1990).

An explanation why the groups were not equal at the beginning of the study is that the one group of more severe patients was in emergency department and the other was in outpatient clinic.

A model based on a linear regression was used. The main assumption is based on: given the initial data, x, these changes over time (second visit) to the observed values yin a linear way. Each group A and B is represented by a straight line. The slope of a line represent the change of recovery. Different slopes mean different rate of recovery. The model answers the question: if the slopes were over all equal, what is the chance of randomly selected data, ending up with slopes as different as actually observed.

Thus, the analysis referred to above is based on a regression model giving two regression lines:

placebo y = [b.sub.1]. x

verum y = ([b.sub.1] + b) x

where

y = difference (visit 1 - visit 2) in mean score

x = Values at visit 1, mean score

This model will give expected values at visit 2 to be compared between the different groups for different initial values as independent variables.

The sinusitis subgroups were analysed by means of a two-sample t test. (The result should be seen more as descriptive due to the small size of the subgroups.)
[] Results

Patient data

 Male Female Mean age SD

Verum 49 51 32.25 11.50
Placebo 55 45 32.80 9.87


One hundred and eight-five patients of the 200 enrolled completed the study. Of the 15 patients who did not complete the study, 10 patients in the placebo and 2 in the treatment group dropped out. In addition, one person in the treatment group had an increase in nasal discharge and epigastric pain, one person complained of a blocked nose, and one of severe headache. These three patients were withdrawn from the study. All of the side effects were judged to be minor and disappeared on the termination of treatment.

Outcome measures: individual mean score (according to protocol improvement)

The results of the individual mean scores, as shown in Table 1 clearly demonstrate two things: (1) a significant difference between the two groups at visit 1, and (2) an extremely low P value for the difference between treatment groups and placebo group, i.e. with respect to the improvement between visit 1 and visit 2 (P < [10.sup.-6]). The differences in mean score between visit 1 and visit 2 for the two groups are shown in Figure 2, where it can be clearly seen that the difference in individual mean symptoms between visit 1 and visit 2 was markedly greater for the treatment group (0.55) than for the placebo group (0.20).

In order to examine to what extent the difference between the initial values influenced the difference in improvement between the treatment group and placebo group, two further analyses were undertaken.

Dependence of result on time of onset of infection

As described above (see Statistical methods), all individuals were divided into three different groups with respect to the onset of infection. The results are shown in Table 2. The table shows that the improvement in the treatment group is significantly greater than the improvement in the placebo group. The P values are also extremely low in this case.

Dependence of result on individual mean scores at visit 1

The ANCOVA analysis shows that the interrelation between 'time of onset' and 'value of initial symptom' did not influence the improvement in health. It further appears that the mean score at visit 1 influenced the improvement at visit 2. But most important is the finding that the analysis also shows that the mean score at visit 1 affected the mean score at visit 2 and did not interfere (i.e. no so-called confounding effects) with the observed difference in improvement between the two groups.

This can also be seen from Figure 3, where the treatment group is clearly more improved than the placebo group for almost the whole range of mean symptoms at visit 1.

Model-based analysis

The reason for a model-based analysis is to test the basic assumption, i.e. whether the treatment implies a difference from the placebo. From the previous analysis it can be concluded that the remaining independent variables (those which could contribute significantly to the result) were:

1. treatment (as opposed to no treatment) and

2. initial value (mean score at visit 1).

A regression model was used to investigate whether and to what extent the placebo group and the treatment group follow the two lines describing the improvement from visit 1 to visit 2. The result gives two different lines, described by:

Placebo: y = 0.267 .x, standard error: 0.023, P value: <<0.001

Treatment: y = 0.840 . x, standard error: 0.061, P value: <<0.001

[R.sup.2] = 0.83

In less technical language, this means that:

- the improvement in the placebo group is, on average, 0.267 per unit of the initial value

- the improvement in the treatment group is, on average, 0.840 units of the initial value.

[R.sup.2] reflects the explanatory power of the model, and [R.sup.2] = 0.83 means that y = (difference visit 1 - visit 2) is as high as 83% explained by the model used, which is a rather high value.

This analysis thus confirms a significant difference in the improvement between treatment group and placebo.

Individual symptoms

In order to achieve more detailed information on the study, the mean values and standard deviations of the individual symptoms were examined (Table 3).

A two-sample t test was used to calculate the P values of the mean differences (visit 1 to visit 2) between treatment and placebo. The result is shown in Table 4.

In this table, six symptoms differ considerably from the others: throat symptom (2), headache (1), nasal symptom (2) and general malaise. Even a cursory look at these mean values indicates that they are responsible for the earlier observed difference in the mean score value between the groups.

However, the mean values in this table are calculated on the basis of so-called ordinal scale variables. A more reliable method is to test the proportional improvement between treatment group and placebo group. Such a calculation is shown in Table 5.

This calculation confirms the result shown in Table 4, demonstrating a pronounced difference in improvement for the same six symptoms: throat symptoms, headache, nasal symptoms and general malaise.

Sinusitis subgroups

Two sinusitis subgroups were selected for a separate analysis. As mentioned above, it was considered meaningful to differentiate between those individuals with a history of episodes of sinusitis ("chronic") and those without, or with very few, previous episodes ("acute"). Eye symptoms and general malaise were not taken into account as they were regarded as less relevant to the symptoms of sinusitis. Table 6 and Figure 4 show the results for the patients with "chronic" sinusitis and Table 7 and Figure 5 the results for the "acute" sinusitis group.

Discussion

The results of the present trials additionally confirms those of previous studies that the Andrographis fixed combination, Kan Jang, is effective against acute upper respiratory tract infections. In contrast to previous clinical studies on the fixed combination, patients with diagnosed sinusitis were included in the study. Due to the lack of background information on a possible effect in sinusitis, it was considered meaningful to divide the patients diagnosed as having sinusitis into two groups, one with a history of sinusitis episodes and the other without. The general thinking was based on the hypothesis that any effect would be more likely in-patients without previous episodes than in those with frequent episodes. Somewhat surprisingly, in this study the efficacy of Kan Jang did not indicate a difference between these two subgroups. However, due to the small number of patients included in the two-sinusitis subgroups, no definite conclusion can be drawn. The results from the study strongly indicate that the Kan Jang fixed combination has a positive effect on sinusitis, but more data are needed for a final conclusion to be made.

In the study as a whole, the main symptoms improved with Kan Jang treatment, i.e. headache and nose and throat symptoms. Also the general malaise was significantly improved in the treatment group. These improvements were also found in the two-sinusitis subgroups.

As the study was double-blind but not randomised, it was important to pay special attention to, and undertake a special analysis of, whether and to what extent the difference in initial values affected the results. Even though the mean score at visit 1 did influence the improvement at visit 2, this score did not interfere with the observed difference in improvement between the two groups. The difference in the individual mean symptom score between visit 1 and visit 2 was 0.55 for the group treated with Kan Jang, and only 0.20 for the placebo group (P < [10.sup.-3]).

The fact that one clinic specialised in otolaryngology and the other was a general acute clinic probably accounts for the difference in the mean initial values, where group B, recruited from the otolaryngology clinic, had a higher mean symptom score.

In conclusion, Kan Jang has a positive effect in the treatment of acute upper respiratory tract infections and also relieves the inflammatory symptoms of sinusitis. The study drug was well tolerated.

[FIGURE 2 OMITTED]

[FIGURE 3 OMITTED]
Table 1. Means and standard deviations of individual mean symptoms.

 Visit 1 Visit 2

Group mean SD mean SD

Treatment (A) n = 95 0.65 0.38 0.09 0.23
Placebo (B) n = 90 0.82 0.50 0.63 0.40

Tests Diff P value Diff P value
A - B -0.17 0.006 -0.54 <0.001


 Difference visit 1-2

Group mean SD

Treatment (A) n = 95 0.55 0.37
Placebo (B) n = 90 0.20 0.27

Tests Duff P value
A - B 0.35 <0.001
 (<[10.sup.-6])

Table 2. Means and standard deviations of individual mean symptoms with
different time (in days) between onset and visit 1.

Onset of infection (in days) Vist 1 Visit 2 Difference
 visit 1

 Time Group Mean SD Mean SD Mean SD n

 0-1 A 0.58 0.35 0.07 0.14 0.50 0.31 53
 0-1 B 0.69 0.49 0.54 0.41 0.13 0.29 46

 2 A 0.70 0.37 0.09 0.23 0.62 0.44 23
 2 B 0.97 0.46 0.66 0.34 0.34 0.22 32

 3-4 A 0.79 0.44 0.18 0.39 0.61 0.45 19
 3-4 B 0.98 0.53 0.91 0.42 0.11 0.17 12

Onset of inf tion (in days) Difference
 visit 1-2

 Time Group P

 0-1 A P < [10.sup.-6]
 0-1 B

 2 A P = 0.009
 2 B

 3-4 A P = 0.0002
 3-4 B

A - verum; B - placebo

Table 3. Single mean symptoms.

 Visit 1 Visit 2

Symptoms Group mean SD mean SD

High temperature A 0.28 0.47 0.08 0.32
 B 0.68 0.73 0.40 0.52
Muscle aches A 0.70 0.92 0.12 0.51
 B 1.13 1.04 0.65 0.80
Cough, frequency A 0.15 0.48 0.01 0.10
 B 0.44 0.74 0.40 0.69
Cough, dry A 0.13 0.34 0.02 0.15
 B 0.22 0.42 0.19 0.40
Cough, productive A 0.08 0.27 0.03 0.18
 B 0.08 0.27 0.09 0.29
Sore throat A 1.00 1.05 0.17 0.65
 B 1.10 1.06 0.91 0.91
Dryness in throat A 0.98 1.06 0.18 0.59
 B 1.26 0.96 1.14 0.87
Headache A 2.01 1.32 0.29 0.77
 B 2.00 1.17 1.42 0.99
Malaise A 2.45 1.50 0.20 0.53
 B 2.49 0.82 2.13 0.98
Catarrh, sneezing A 1.73 1.20 0.20 0.54
 B 1.67 1.20 1.27 1.01
Catarrh, running A 0.77 1.02 0.12 0.51
 B 1.09 1.11 0.83 0.99
Catarrh, purulent A 0.59 1.09 0.04 0.33
 B 0.47 0.79 0.45 0.75
Eyes, dry A 0.02 0.14 0.00 0.00
 B 0.13 0.50 0.10 0.48
Eyes, running A 0.14 0.41 0.00 0.00
 B 0.28 0.57 0.12 0.33
Eyes, purulent A 0.00 0.00 0.00 0.00
 B 0.00 0.00 0.01 0.11

Table 4. Test of mean differences visit 1 to visit 2 between treatment
and placebo.

Symptoms mean Standard error P value

High temperature -0.09 0.09 0.273
Muscle aches 0.04 0.11 0.74
Cough, frequency 0.06 0.07 0.40
Cough, dry 0.10 0.05 0.052
Cough, productive 0.08 0.03 0.014
Sore throat 0.61 0.12 <0.001
Dryness in throat 0.71 0.14 <0.001
Headache 1.15 0.18 <0.001
Malaise 1.76 0.23 <0.001
Catarrh, sneezing 1.04 0.14 <0.001
Catarrh, running 0.38 0.15 0.010
Catarrh, purulent 0.59 0.12 <0.001
Eyes, dry -0.01 0.003 0.64
Eyes, running -0.05 0.07 0.47
Eyes, purulent 0.01 0.01 0.32

Table 5. Proportions for improvement and worsening visit 1 to visit 2
and test for differences between treatment and placebo.

 Worsening

Symptoms [P.sup.-.sub.A] [P.sup.-.sub.B] P Value

High temperature 0.02 0.06 0.19
Muscle aches 0.02 0.01 0.60
Cough, frequency 0.00 0.04 0.06
Cough, dry 0.01 0.05 0.13
Cough, productive 0.00 0.04 0.09
Sore throat 0.01 0.04 0.20
Dryness in throat 0.03 0.12 0.02
Headache 0.03 0.10 0.053
Malaise 0.00 0.10 0.01
Catarrh, sneezing 0.01 0.03 0.34
Catarrh, running 0.01 0.12 0.003
Catarrh, purulent 0.00 0.07 0.011
Eyes, dry 0.00 0.01 0.37
Eyes, running 0.00 0.01 0.34
Eyes, purulent 0.00 0.01 0.35

 Improvement

Symptoms [P.sup.+.sub.A] [P.sup.+.sub.B] P Value

High temperature 0.22 0.38 0.021
Muscle aches 0.39 0.44 0.50
Cough, frequency 0.11 0.10 0.80
Cough, dry 0.13 0.06 0.12
Cough, productive 0.04 0.00 0.09
Sore throat 0.52 0.27 0.0004
Dryness in throat 0.48 0.22 0.0002
Headache 0.78 0.49 0.0001
Malaise 0.75 0.39 0.0001
Catarrh, sneezing 0.72 0.48 0.0006
Catarrh, running 0.45 0.42 0.69
Catarrh, purulent 0.28 0.06 0.0001
Eyes, dry 0.02 0.04 0.45
Eyes, running 0.12 0.18 0.25
Eyes, purulent 0.00 0.00 -

Table 6. "Chronic" sinusitis-group (Two-sample t test).

Symptoms Group A, n = 26 Group A, n = 26
 before treatment after treatment

 A1 A2

Temperature 1.2310 [+ or -] 0.1009 1.0000 [+ or -] 0.0000
Muscle aches 0.3846 [+ or -] 0.1476 0.0000 [+ or -] 0.0000
Cough 0.1538 [+ or -] 0.0721 0.0000 [+ or -] 0.0000
Sore throat 0.5769 [+ or -] 0.1769 0.0000 [+ or -] 0.0000
Dryness in throat 0.6154 [+ or -] 0.2224 0.0000 [+ or -] 0.0000
Headache 2.3850 [+ or -] 0.2778 0.3077 [+ or -] 0.1332
Sneezing 1.5770 [+ or -] 0.2670 0.0769 [+ or -] 0.0533
Running 0.5000 [+ or -] 0.1776 0.1923 [+ or -] 0.1571
Purulent 1.0380 [+ or -] 0.2510 0.1538 [+ or -] 0.1202

Compared columns A1-B1 A1-A2
P value 0.1315 0.0084

Are means
significantly No, ns Yes **
different? (P < 0.05) t = 1.680 t = 3.470

Mean of differences -0.2078 0.7479
R squared 0.6008 0.2607

Symptoms Group B, n = 18 Group B, n = 18
 before treatment after treatment

 B1 B2

Temperature 1.2222 [+ or -] 0.1292 1.3889 [+ or -] 0.1432
Muscle aches 0.7222 [+ or -] 0.1948 0.4444 [+ or -] 0.1661
Cough 0.2778 [+ or -] 0.1086 0.2778 [+ or -] 0.1086
Sore throat 0.8889 [+ or -] 0.2271 0.6667 [+ or -] 0.1617
Dryness in throat 1.1110 [+ or -] 0.1962 1.2220 [+ or -] 0.2222
Headache 2.0000 [+ or -] 0.2557 1.5560 [+ or -] 0.2826
Sneezing 1.9440 [+ or -] 0.2057 1.6110 [+ or -] 0.1645
Running 1.3330 [+ or -] 0.3333 1.1110 [+ or -] 0.2410
Purulent 0.8333 [+ or -] 0.2459 0.8889 [+ or -] 0.2788

Compared columns B1-B2 A2-B2
P value 0.1100 0.0005

Are means
significantly No, ns Yes ***
different? (P < 0.05) t = 1.791 t = 5.694

Mean of differences 0.1295 -0.8262
R squared 0.2863 0.8021

A - verum; B - placebo

Table 7. Acute sinusitis (Two-sample t test).

Symptoms Group A, n = 9 Group A, n = 9
 before treatment after treatment

 A1 A2

Temperature 1.5560 [+ or -] 0.1757 1.0000 [+ or -] 0.1260
Muscle aches 1.2220 [+ or -] 0.3643 0.0000 [+ or -] 0.0000
Cough 0.3333 [+ or -] 0.1667 0.0000 [+ or -] 0.0000
Sore throat 0.7778 [+ or -] 0.2778 0.0000 [+ or -] 0.0000
Dryness in throat 1.2220 [+ or -] 0.3643 0.0000 [+ or -] 0.0000
Headache 2.7780 [+ or -] 0.2778 0.3333 [+ or -] 0.2357
Sneezing 2.2222 [+ or -] 0.4339 0.0000 [+ or -] 0.0000
Running 0.7778 [+ or -] 0.3643 0.3333 [+ or -] 0.2357
Purulent 0.2222 [+ or -] 0.1470 0.0000 [+ or -] 0.0000

Compared columns A1-B1 A1-A2
P value 0.0001 0.0047

Are means
significantly Yes, *** Yes **
different? (P < 0.05) t = 7.015 t = 3.882

Mean of differences 0.6839 1.049
R squared 0.8602 0.6532

Symptoms Group B, n = 15 Group B, n = 15
 before treatment after treatment

 B1 B2

Temperature 2.3330 [+ or -] 0.1594 1.6670 [+ or -] 0.1260
Muscle aches 2.0670 [+ or -] 0.2667 1.1330 [+ or -] 0.2153
Cough 0.8667 [+ or -] 0.1919 0.9333 [+ or -] 0.2482
Sore throat 1.9330 [+ or -] 0.3003 1.4000 [+ or -] 0.2350
Dryness in throat 1.9330 [+ or -] 0.2840 1.4670 [+ or -] 0.2364
Headache 3.1330 [+ or -] 0.2557 2.2670 [+ or -] 0.1817
Sneezing 2.4670 [+ or -] 0.2364 1.8670 [+ or -] 0.2557
Running 1.3330 [+ or -] 0.3737 0.8667 [+ or -] 0.2737
Purulent 1.2000 [+ or -] 0.2619 1.2000 [+ or -] 0.2225

Compared columns B1-B2 A2-B2
P value 0.0024 <0.0001

Are means
significantly Yes ** Yes ***
different? (P < 0.05) t = 4.355 t = 7.644

Mean of differences 0.4961 -1.237
R squared 0.7034 0.8796

** P [less than or equal to] 0.01; *** P [less than or equal to]0.001

Fig. 1. Patient evaluation form.

Temperature 1 <37
 2 37-38
 3 38-39
 4 <39 (exclusion)

Headache 0 No
 1 Mild
 2 Moderate
 3 Severe
 4 Very severe

Muscle aches 0 No
 1 Mild
 2 Moderate
 3 Pronounced
 4 Very pronounced

Sore throat 0 No
 1 Mild
 2 Moderate
 3 pronounced
 4 Very pronounced
 5 Unbearable

Dry throat 0 No
 1 Mild
 2 Moderate
 3 Pronounced
 4 Very pronounced

Cough, frequency 0
 1

Cough, dryness 0
 1

Cough, productive 0
 1

Malaise 0 None
("catarrh") 1 Slight
 2 Moderate
 3 Pronounced
 4 Very pronounced
 5 Exceptionally severe

Sneezing 0 None
 1 Infrequent, mild
 2 More frequent, mild
 3 Moderate
 4 Pronounced, quite frequent
 5 Very pronounced and frequent

Running nose 0 No
 1 Not so much
 2 Moderate
 3 Pronounced
 4 Very pronounced

Purulent 0 No
 1 Mild
 2 Moderate
 3 Pronounced
 4 Very pronounced

Dry eyes 0
 1

Runnings eyes 0
 1

Purulent eyes 0
 1

Fig. 4. Two-sample test.

Total level of inflammatory symptoms in scores

 A1 A2 B1 B2

Mean 0.9402 0.1923 1.148 1.019
Coefficient 74.69% 167.34% 48.75% 47.16%
of variation


[GRAPH OMITTED]
Fig. 5. Two-sample t test.

Total level of inflammatory symptoms in points

 A1 A2 B1 B2

Mean 1.235 0.1852 1.918 1.422
Coefficient 68.46% 182.49% 36.56% 31.97%
of variation


[GRAPH OMITTED]

References

Amroyan E, Gabrielian E, Panossian A, Wikman G, Wagner H (1999) Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation. Phytomedicine 6(1): 27-31

Caceres D, Hancke J, Burgos R, Sandberg F, Wikman G (1999) Use of visual analogue scale measurements (VAS) to assess the efficacy of standardized Andrographis paniculata extract SHI-10 in reducing the symptoms of common cold. A randomized double-blind placebo-controlled study. Phytomedicine 6(4):1-6

Caceres D, Hancke J, Burgos RA, Sandberg F, Wikman G (1997) Prevention of common colds with Andrographis paniculata dried extract: A pilot double blind study. Phytomedicine 4(2):101-104

Hancke J, Burgos R, Caceres D (1995) Double-blind study with a new monodrug Kan Jang: Decrease of symptoms and Improvement in the recovery from common colds. Phytotherapy Research 9:559-562

Kulichenko LL, Kireyeva LV, Malyshkina EN, Wikman G (2001) Two randomized parallel group studies with control group of Kan Jang phytopreparation in patients with influenza during influenza epidemics in the city of Volgograd in February, 1999 and January - February, 2000. (Submitted for publication, 2001)

Madav S, Tandan J, Tripahti H (1996) Anti-inflammatory activity of andrographolide. Phytotherapy Research 67(5):452-458

McCall RB (1990) Fundamental Statistics for the Behavioural Sciences, 5th ed. New York, Harcourt Brace Jovanovich

Melchior J, Palm S, Wikman G (1997) Controlled clinical study of standardized Andrographis paniculata extract in common cold - a pilot trial. Phytomedicine 3(4):315-318

Melchior J, Spasov AA, Ostrovskij OV, Bulanov AE, Wikman G (2000) Double blind placebo controlled pilot and Phase III study of a standardized Andrographis paniculata Herba Nees extract fixed combination (Kan Jang) in the treatment of uncomplicated upper respiratory tract infection. Phytomedicine 7(5): 341-350

Puri A, Saxena R, Saxena RP, Saxena KC (1993) Immunostimulant agents from Andrographis paniculata. J. Nat. Prod. 56(7):995-999

E.S. Gabrielian (2), A.K. Shukarian (1), G.I. Goukasova (1) G.L. Chandanian (1), A.G. Panossian (2), G. Wikman (3), and H. Wagner (4)

(1.) "Erebuni", Medical Centre, Yerevan Armenia

(2.) Drug and Medicinal Technology Agency of the Ministry of Health of Armenia

(3.) Swedish Herbal Institute, Vastra Frolunda, Sweden

(4.) Department of Pharmacy, Center of Pharmaresearch, University, Munich, Germany

Address

G. Wikman, Swedish Herbal Insitute, Gruvgatan 37, 421-30 Vastra Frolunda, Sweden Tel.: ++46-31-3396680; Fax: ++46-31-3396699; e-mail: christina.holm@shi.se
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Author:Gabrielian, E.S.; Shukarian, A.K.; Goukasova, G.I.; Chandanian, G.L.; Panossian, A.G.; Wikman, G.; W
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Date:Oct 1, 2002
Words:5434
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