This study was designed to determine the therapeutic efficacy and safety of the Shi-cha capsule, a Chinese herbal formula, in the treatment of patients with wind-cold type common cold. In our multi-center, prospective, double-blind, randomized, placebo-controlled, dose-escalation trial, patients with wind-cold type common cold received 0.6 g of Shi-cha capsule plus 0.6 g placebo (group A), 1.2 g of Shi-cha capsule (group B), or 1.2 g placebo (group C), three times daily for 3 days and followed up to 10 days. The primary end point was all symptom duration. The secondary end points were main symptom duration, minor symptom duration, the changes in cumulative symptom score, main symptom score, and minor symptom score 4 days after the treatment, as well as adverse events. A total of 377 patients were recruited and 360 met the inclusive criteria; 120 patients constituted each treatment group. Compared with patients in group C, patients in groups A and B had significant improvement in the all symptom duration, main symptom duration, minor symptom duration, as well as change from baseline of cumulative symptom score, main symptom score, and minor symptom score at day 4. The symptom durations and scores showed slight superiority of group B over group A, although these differences were not statistically significant. There were no differences in adverse events. The Shi-cha capsule is efficacious and safe for the treatment of patients with wind-cold type common cold. Larger trials are required to fully assess the benefits and safety of this treatment for common cold.
The common cold is frequent both in the developed and developing countries with the symptom of nasal congestion and discharge, sneezing, mild fever, cough, headache, and malaise, and it is caused by over 200 viruses or bacteria [
Traditional Chinese medicine (TCM) is a 3000-year-old holistic system of medicine that combines medical herbs, acupuncture, food therapy, massage, and therapeutic exercise for both extensive treatment and prevention of diseases, including common cold. Dissatisfaction with treatments offered by Western medicine has led many patients to turn to for treating common cold in China and other parts of the world, but the quality of reported studies is of great concern [
Shi-Cha capsule (SCC) is a new traditional Chinese prescription and manufactured by the Yunnan Institute of Materia Medica, Yunnan, China. It composes of Shi Jiaocao (
A multicenter, prospective, randomized, double-blind, placebo-controlled, dose-escalation phase II clinical trial was designed to determine the therapeutic efficacy and safety of 0.6 g and 1.2 g of SCC given three times daily for 3 days to patients with wind-cold type common cold. The protocol was reviewed and approved by the independent ethics committees at West China Hospital of Sichuan University (no. TCM-2010-03). In addition, the trial was registered with the Chinese Clinical Trial Registry (no. ChiCTR-TRC-12002296) and was conducted in accordance with the Good Clinical Practice Guidelines and the Declaration of Helsinki [
A total of 377 eligible patients were recruited from five centers in China between November 2010 and March 2011. All patients were examined by one of the clinical study respiratory experts and were enrolled into the study according to the inclusion and exclusion criteria described in Table
Inclusion and exclusion criteria.
Inclusion criteria | |
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(1) 18 to 65 years of age | |
(2) Diagnosis of common cold by a respiratory expert according to relevant criteria and the syndrome criteria of wind-cold type in TCM† | |
(3) Patient within 48 hours of onset of common cold-like illness | |
(4) Patient must be able to understand and give written informed consent and report adverse events and concomitant medication for the duration of the study | |
| |
Exclusion criteria | |
| |
(1) Patient has suffered from acute viral pharyngitis or laryngitis, acute herpetic pharyngitis or laryngitis, acute conjunctivitis, as well as acute tonsillitis, and so forth | |
(2) Patient has taken any medication for relief of symptoms prior to study initiation | |
(3) Patient who has fever (>38.5°C) | |
(4) Patient who is on analgesic or anti-inflammatory regimen requiring treatment with analgesics, nonsteroidal anti-inflammatory drugs, or steroids | |
(5) Patient is pregnant, nursing, or a woman of childbearing potential not practicing adequate contraception. Women, who are uncertain if they are pregnant, may participate in the study, if they undergo a pregnancy test, which shows a negative result | |
(6) Patient has comorbid condition, uncontrolled metabolic condition or psychiatric condition that might make tolerance or evaluation of the symptoms difficult |
†TCM: traditional Chinese medicine.
A total of 360 of eligible patients met the inclusive criteria and were randomized into group A (0.6 g × 2 capsules of SCC plus 0.6 g × 2 capsule of placebo), group B (1.2 g × 4 capsules of SCC), or group C (1.2 g × 4 capsules of placebo). 120 patients were required placed into each treatment group. Randomization was conducted in blocks of five in a 1 : 1 : 1 ratio using the PRCO PLAN function of the analysis system of SAS (version 6.12 for Windows) by an independent provider not involved in this study. The randomization lists were placed in two sealed envelopes, and the details were unknown to the study investigators and the patients throughout the course of the study. One envelope was kept by Yunnan Institute of Materia Medica (Yunan Province, China), and the other was kept at the study centers to be opened in case of medical emergency.
All randomized patients in group A were required to take 0.6 g of SCC plus 0.6 g placebo three times daily for 3 days; those in group B took 1.2 g of SCC three times daily for 3 days; and those in group C took 1.2 g of placebo three times daily for 3 days. Patients with common cold were diagnosed with “wind-cold type” (which was an inclusion criteria), the corresponding management was designed to disperse wind-evil and dispel cold as well as supplement
Standard formula of SCC.
Chinese name | Pharmaceutical name | The principle of prescription | Source | Pharmacological actions in TCM |
---|---|---|---|---|
Shi Jiaocao |
|
Primary ingredients in a prescription | The dried whole plant of |
To dispel wind and dry dampness, to regulate |
Xiao Shancha |
|
Minister herb | The dried whole plant of |
To relieve exterior by diaphoresis, to clear away heat-dampness and promote diuresis, to regulate |
Huang Qi |
|
Minister herb | The dried root of |
To tonify |
Yu Xingcao |
|
Adjuvant and messenger herb | The dried whole plant of |
To clear away heat-toxin caused by common cold |
Qian Liguang |
|
Adjuvant and messenger herb | The dried whole plant of |
To clear away heat-toxin caused by common cold |
Qiang Huo |
|
Adjuvant and messenger herb | The dried rhizome and root of |
To remove dampness to relieve pain caused by common cold |
SCC: Shi-Cha capsule; TCM: traditional Chinese medicine;
Patients completed the symptom questionnaire from baseline to day 10 after treatment. These data provided an assessment of all symptom duration, main symptom duration, minor symptom duration, main symptom score, minor symptom score, and cumulative symptom score. The questionnaire consisted of eight symptoms: avertion to cold, clear nasal discharge, arthralgia of extremities, fever, headache, stuffy nose, sneezing, and spiritlessness and weakness. The first two symptoms were main symptom for which the patients provided a graded score (not at all = 0, mild = 3, moderate = 6, severe = 9). The last six symptoms were minor symptom for which the patients provided a graded score (not at all = 0, mild = 1, moderate = 2, severe = 3). The cumulative symptom score was the main symptom score plus the minor symptom score. In addition, tongue proper, tongue fur, and pulse were also assessed (see Supplementary Material 2).
The primary end point was defined as duration of all symptom. The secondary end points were main symptom duration, minor symptom duration, the changes in main symptom score, minor symptom score, and cumulative symptom score 4 days after the treatment, as well as adverse events. Duration was defined as the number of hours from study enrollment to the last day before the patient answered “No” to the question “Do you think that you are still sick today?”
In light of the study procedure, patients were seen by a respiratory expert at baseline, day 4, and day 10. During each visit, patients were interviewed by the respiratory expert to ascertain symptoms, compliance, and occurrence of adverse events. In addition, they were in contract with the enrolling research assistant and respiratory expert by telephone throughout the study except for interview. Adherence was assessed by capsule counts and by the daily questionnaire (which asked the patients whether they had taken their capsules and how many capsules they had taken). Adverse events and compliance were monitored. Clinical laboratory evaluation, including routine blood, urine, and stool tests along with hepatic and renal functions, and electrocardiogram, were examined at baseline and at day 4 after treatment to assess the safety of the treatment used for each group.
Based on our experience with TCM in treating common cold and on other similar studies in the literature [
All data were documented with Epidata 3.0 by two independent individuals, and the files were locked. The intent-to-treat (ITT) population included all randomized patients who received study medication and attended at least one study visit after the start of treatment. Per-protocol (PP) analysis included all randomized patients who completed study medication and followedup after the start of treatment. The analysis of efficacy was performed in the ITT and PP populations. All quantitative data were expressed as mean ± standard deviation (SD), and one-way analysis of variance (ANOVA) was used to compare the data. A Chi-square test or Fisher’s exact test was performed to calculate differences in qualitative data between the three groups. A Kruskal-Wallis
A total of 377 patients were recruited during a period of five months from November 2010 to March 2011, 360 of these patients met the inclusive criteria, and 120 patients were placed into each treatment group. A total of 26 patients (7.22%) withdrew during the course of the trial: 7 (5.83%) in group A, 7 (5.83%) in group B, and 12 (10%) in group C, respectively (
Demographic data and baseline characteristics: intent-to-treat analysis.
Group A ( |
Group B ( |
Group C ( |
|
| |
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Sex ratio (male/female) | 71/43 | 76/41 | 75/40 | 0.263 | 0.877† |
Age (years) (mean ± SD) | 35.98 ± 12.453 | 36.12 ± 12.465 | 35.64 ± 12.135 | 0.046 | 0.955‡ |
Body weight (kg) (mean ± SD) | 61.12 ± 10.514 | 60.23 ± 8.855 | 58.98 ± 9.827 | 1.387 | 0.251‡ |
Height (cm) (mean ± SD) | 164.63 ± 8.223 | 164.36 ± 7.750 | 164.11 ± 8.266 | 0.118 | 0.889‡ |
Body temperature (°C) (mean ± SD) | 36.95 ± 0.451 | 36.90 ± 0.481 | 36.98 ± 0.507 | 0.855 | 0.426‡ |
Course (hours) (mean ± SD) | 22.75 ± 11.096 | 24.21 ± 12.104 | 23.42 ± 11.477 | 0.516 | 0.772¶ |
Main symptoms score (mean ± SD) | |||||
Avertion to cold | 4.68 ± 1.741 | 4.59 ± 1.698 | 4.85 ± 1.713 | 1.477 | 0.478¶ |
Nasal discharge | 5.58 ± 1.991 | 5.26 ± 1.844 | 5.69 ± 2.002 | 2.836 | 0.242¶ |
Minor symptoms score (mean ± SD) | 0.478¶ | ||||
Arthralgia of extremities | 1.33 ± 0.816 | 1.26 ± 0.770 | 1.28 ± 0.779 | 0.298 | 0.861¶ |
Fever | 0.45 ± 0.705 | 0.40 ± 0.732 | 0.49 ± 0.788 | 1.080 | 0.583¶ |
Headache | 1.01 ± 0.735 | 1.04 ± 0.781 | 0.97 ± 0.725 | 0.492 | 0.782¶ |
Stuffy nose | 1.66 ± 0.762 | 1.47 ± 0.677 | 1.64 ± 0.752 | 4.082 | 0.130¶ |
Sneezing | 1.38 ± 0.803 | 1.52 ± 0.690 | 1.42 ± 0.827 | 2.338 | 0.311¶ |
Spiritlessness and weakness | 1.18 ± 0.771 | 1.25 ± 0.684 | 1.29 ± 0.758 | 1.102 | 0.576¶ |
Cumulative symptoms score (mean ± SD) | 17.27 ± 4.700 | 16.79 ± 4.333 | 17.63 ± 4.979 | 0.962 | 0.383‡ |
†Chi-square test.
‡One-way analysis of variance.
¶Kruskal-Wallis
Flow chart of patient disposition. ITT: intent-to-treat; PP: per-protocol analysis.
For cohort patients, there was a significant difference in all symptom duration and main symptom duration among three Groups both the ITT and PP analyses (Figures
The duration of symptom for patients with wind-cold type common cold receiving 0.6 g SCC (group A), 1.2 g SCC (group B), or 1.2 g placebo (group C). (a) All symptom duration; (b) and (c) the duration of avertion to cold; (d) and (e) the nasal discharge.
In addition, the main symptom duration and minor symptom duration were determined between patients with SCC treatment and without. There was a significant difference in main symptom duration (Figures
In addition to evaluate the duration of symptom, the symptom score was also compared among three Groups. An improvement in cumulative and individual symptom score was observed from baseline to day 10 in all three groups. The changes from baseline of symptom score at day 4 were compared because the most significant changes in cumulative symptom score and individual symptom score occurred at day 4 after treatment among three groups (Figure
The symptom score for patients with wind-cold type common cold receiving 0.6 g SCC (group A), 1.2 g SCC (group B), or 1.2 g placebo (group C). (a) The cumulative symptom score; (b) the avertion to cold score; (c) the clear nasal discharge score; (d) the arthralgia of extremities score; (e) the fever score; (f) the headache score; (g) the stuffy nose score; (h) the sneezing score; and (i) the spiritlessness and weakness score.
Compared with patients in group C, the ITT and PP analyses showed that patients in groups A and B had significant improvement in change from baseline of cumulative symptom score, main symptom score, and minor symptom score at day 4 (
Intent-to-treat and per-protocol analyses of main symptom score, minor symptom score, and cumulative symptom score.
Intent-to-treat analysis | Change from baseline to day 4 (mean ± SD) | ||
---|---|---|---|
Group A ( |
Group B ( |
Group C ( | |
Main symptom score | 8.842 ± 3.453 | 8.513 ± 3.050 | 7.330 ± 4.209 |
|
<0.0001 | <0.0001 | |
Minor symptom score | 5.851 ± 2.839 | 6.120 ± 2.443 | 5.157 ± 2.648 |
|
<0.0001 | <0.0001 | |
Cumulative symptom score | 14.320 ± 5.577 | 13.890 ± 4.949 | 11.920 ± 6.090 |
|
<0.0001 | <0.0001 | |
| |||
Per-protocol analysis | Group A ( |
Group B ( |
Group C ( |
| |||
Main symptom score | 8.920 ± 3.365 | 8.522 ± 3.094 | 7.417 ± 4.212 |
|
<0.0001 | <0.0001 | |
Minor symptom score | 5.876 ± 2.838 | 6.053 ± 2.394 | 5.241 ± 2.696 |
|
<0.0001 | <0.0001 | |
Cumulative symptom score | 14.420 ± 5.498 | 13.850 ± 5.016 | 12.060 ± 6.143 |
|
<0.0001 | <0.0001 |
There were no deaths during the study. There were one, one, and two patients with adverse effects in group A, group B, and group C, respectively (
To our knowledge, this is the first large randomized, prospective, double-blind, placebo-controlled, dose-escalation trial designated to evaluate the efficacy and safety of TCM in an adult population from China. Our study demonstrated that SCC was efficacious and safe for the management of wind-cold type common cold. Patients receiving 0.6 g and 1.2 g of SCC treatment three times daily demonstrated significant improvement in the symptom duration and change from baseline of symptom score compared to patients receiving the placebo at day 4. Patients receiving 1.2 g of SCC three times daily showed a slight benefit in their symptom duration and change from baseline of symptom score over patients receiving 0.6 g of SCC three times daily during treatment, although this difference was not statistically significant.
To date, there are no validated strategies for the treatment of common cold, and current therapy focuses on symptom relief. This has led to high patient dissatisfaction and frustration with current treatments for common cold. Thus, there is a need for simple, safe, and effective first-line therapies to treat the multiple symptoms of patients with this disorder. TCM stresses differentiation of symptoms and signs; it considers the human being to be an organic entirety and treatment should be emphasized on the entirety. Besides, TCM counts on the synergetic effects of the herbs, which have a general spectra of action. Therefore, TCM practitioners usually use a substantial number of herbs to treat various conditions including common cold, and this will overcome the shortcomings of Western medicine.
TCM theory holds that lung is in charge of skin and hair and keeps the dispersing function, skin and hair damage will result in dysfunction of lung with defensive
The SCC formula contains six herbs including
Popular opinion confirms that the general public believes TCM to be safe, to cause fewer side effects, and to be less likely to cause dependency. In our study, only two patients who were receiving 0.6 g and 1.2 g of SCC three time daily reported light upper abdominal pain, respectively. Therefore, we concluded that there was no significant correlation between the use of the SCC and adverse events. Nevertheless, many herbs can be toxic, especially in high quantities and with frequent use. Furthermore, herb-synthetic drug interactions can be problematic. Hence, the analysis of adverse effects of TCM for treating common cold is indeed very important.
This study had some potential weaknesses. Only SCC formula for the treatment of common cold with wind-cold type was determined in this study, the outcomes could not be generalized to other herbal formula for the treatment of common cold or other types. The formulation and dosage of SCC standardized, which might not fully reflect the normal practice of TCM which often alters the formula by removing or adding specific herbs according to the patient’s body constitution. However, this finding supports the premise that it was of sufficient study to assess the benefit and safety of TCM for the treatment of common cold.
In conclusion, during a treatment period of 3 days, the SCC significantly improved the symptom duration and the changes in symptom score in patients with wind-cold type common cold. Patients receiving 1.2 g of SCC three times daily showed a slight benefit of these end points over patients receiving 0.6 g of SCC three times daily during treatment, although this difference was not statistically significant. Larger trials are required to fully assess the benefits and safety of the use of the two dosages of the SCC for treating wind-cold type common cold.
No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this paper.
The authors particularly thanked Chen Yan and Feng Min, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, West China School of Medicine, Sichuan University, for their care of these patients. They thanked Dr. Lei Deng and Professor. Guan-Jian Liu at the West China Hospital, West China School of Medicine, Sichuan University, for his suggestion and statistical assistance as well as Yunnan Institute of Materia Medica (Yunan Province, China) for providing the Yun-chang capsule. This work was supported by the Science and Technology Program Foundation of Yunnan Province (no. 2009BC011) and the Natural Science Foundation of West China Hospital, West China School of Medicine, Sichuan University (no. 141080262). No benefits in any form have been or will be received from a commercial party directly or indirectly related to the subject of this article. The trial was registered with the Chinese Clinical Trial Registry: