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SARS: Clinical Trials on Treatment Using a Combination of Traditional Chinese Medicine and Western Medicine
(2004; 194 pages) View the PDF document
Table of Contents
View the documentAcknowledgements
View the documentIntroduction
View the documentReport of the International Expert Meeting to review and analyse clinical reports on combination treatment for SARS
View the documentReport 1: Clinical research on treatment of SARS with integrated Traditional Chinese medicine and Western Medicine
View the documentReport 2: Clinical efficacy of the treatment of SARS with integrated Traditional Chinese medicine and Western medicine: an analysis of 524 cases
View the documentReport 3: Manifestation of symptoms in patients with SARS and analysis of the curative effect of treatment with integrated Traditional Chinese medicine and Western medicine
View the documentReport 4: Clinical study on 103 inpatients undergoing therapy with integrated Traditional Chinese medicine and Western medicine
View the documentReport 5: Clinical observations of 11 patients with SARS treated with Traditional Chinese medicine
View the documentReport 6: Effects of applying integrated therapy with Traditional Chinese medicine and Western medicine on liver and kidney functions in patients with SARS
View the documentReport 7: Clinical research on 63 patients with SARS treated with integrated Traditional Chinese medicine and Western medicine
View the documentReport 8: Influence of integrated therapy with Traditional Chinese medicine and Western medicine on lymphocytes and T-lymphocyte subpopulations of patients with SARS
View the documentReport 9: Analysis of the clinical curative effects on patients with SARS of treatment with Traditional Chinese medicine and Western medicine
View the documentReport 10: Evaluation of clinical curative effects of Traditional Chinese medicine in treatment of patients convalescing from SARS
View the documentReport A: A herbal formula for the prevention of transmission of SARS during the SARS epidemic in Hong Kong Special Administrative Region - a prospective cohort study
View the documentReport B: Effects of Chinese medicine on patients convalescing from SARS in Hong Kong special administrative region - a prospective non-randomized controlled trial
View the documentReport C: Traditional Chinese medicine in the management of patients with SARS in Hong Kong Special Administrative Region - a case-control study of 24 patients
View the documentAnnex
 

Report 7: Clinical research on 63 patients with SARS treated with integrated Traditional Chinese medicine and Western medicine

Zhang Yunling25, Zhang Xiaomei25, Jin Yaowen26, Yang Zhufu27, Tan Xiangheng28, Zhang Ying29, Wang Meiying29, Yang Yukun30, Zhang Yang31, Liu Xiaosu31, Wang Yulai25, Jin Zhang’an25, Lin Qian25, Liu Wenna25, Guo Xiaoqiang32, Xiong Fuhua32, Zhang Changzeng26, Pan Shuli26, Ma Yunming26, Feng Guilan26, He Liping32, He Yuehui29, Li Hongyan29 and Guo Quan32

25 Oriental Hospital of Beijing University of Traditional Chinese Medicine
26 Beijing Fengtai District Nanyuan Hospital
27 Bo’ai Hospital of China Association for Disabled
28 Beijing Fengtai District Tieyin Hospital
29 Beijing Fengtai District Changxindian Hospital
30 Beijing Fengtai District Puhuangyu Hospital
31 Beijing Fengtai District Bureau of Health
32 Beijing Fengtai Hospital


Abstract The objective was to evaluate the clinical curative effects of Traditional Chinese medicine (TCM) regimens 1, 2 and 3 integrated with basic Western medicine in treatment of severe acute respiratory syndrome (SARS). In line with the diagnostic criteria for SARS issued by the Chinese Centre for Disease Control and Prevention, criteria for inclusion and exclusion of cases were decided upon. Sixty-three patients with clinically confirmed SARS were selected and divided into normal cases and serious cases according to the severity of their illness, and were randomly assigned either to the integrated treatment group (31 cases) or the group treated with Western medicine (32 cases). The course of the illness was divided into three stages in accordance with the natural progression and clinical manifestations of SARS (namely, the high fever stage, the dyspnoea and cough stage, and the absorption stage). In the integrated treatment group, in addition to standard treatment, patients were instructed to take oral preparations of SARS regimens 1, 2 or 3, for the high fever stage, the dyspnoea and cough stage, and the absorption stage, respectively. Patients in the group treated with Western medicine received standard treatment. Monitoring of general symptoms and signs caused by fever, chest X-ray films, the results of routine blood examinations and blood biochemical tests, hormone doses and other indicators was carried out for 21 days. Therapy with the integrated treatment can obviously alleviate general toxic symptoms and promote absorption of pulmonary inflammation; when compared with the effects in the group treated with Western medicine alone the differences were significant. Clinical curative effects were achieved through the administration of integrated TCM and Western medicine and no obvious side-effects were observed.

Introduction

Beijing was one of the areas hardest hit by the epidemic of SARS accounting for over 50% of the total morbidity recorded for the whole country. After the end of April 2003, the rapid spread of SARS had led to about 100 new cases in Beijing every day.

After full consultation and advice from a number of experts in TCM and according to the clinical features and the different pathological stages of SARS, a preliminary explanation of the pathogenesis and etiology of SARS from the point of view of TCM was put forward, and SARS regimens 1, 2 and 3 were developed. In accordance with the principles for clinical research design, prospective clinical observation proposals were made and 63 eligible confirmed cases were studied.

Methods

Study subjects

Case sources

All participants were patients with clinically confirmed SARS from Beijing Changxindian Hospital, a specially designated hospital for SARS patients, and all the patients had been reported to the China Centre for Disease Prevention and Control as required by the relevant regulations. The observation period was from 21 April to 20 May 2003. Of the 63 cases, 29 were female and 34 were male, with an average age of 41 ± 8.3 years; 16 of the patients had normal SARS and 47 serious SARS.

Criteria for diagnosis

The criteria given in the Guide to clinical work in respect of infectious SARS were adopted. They were developed by the China Centre for Disease Prevention and Control and published by Beijing SARS Treatment and Command Centre on 27 April 2003.

Criteria for inclusion

Patients were included in the study if:

• they met the diagnostic criteria;
• were aged between 18 and 65 years old;
• the onset of disease was no more than 5 days before the start of the study; and
• they could be categorized as being normal or serious cases.


Criteria for exclusion

Patients were not eligible to participate in the study if they:

• had extremely severe disease, were suffering from shock, acute respiratory distress syndrome (ARDS) or multiple organ dysfunction (MODS);

• had severe cardiovascular diseases with serious complications, cerebrovascular diseases, liver diseases, kidney diseases, blood system diseases, endocrine system diseases, nervous system diseases or neuropsychosis;

• were aged less than 18 years or more than 65 years;

• were pregnant or lactating; or

• had a history of food or drug allergy.


Allocation to the treatment groups

The patients included in the study were grouped by means of a hierarchical random grouping method. The serious cases and normal cases were grouped separately, and then lots were drawn. Twenty-four pairs of patients were divided into lot 1 and lot 2 for the serious cases and eight pairs of patients divided into lot 1 and lot 2 for the normal cases, giving a total of 32 pairs. Cases drawn with serious case lot 1 or normal case lot 1 formed the integrated treatment group, whereas those with serious case lot 2 or common case lot 2 comprised the group treated with Western medicine. The integrated treatment group consisted of 31 patients of whom 24 had serious and seven had normal SARS. The group treated with Western medicine consisted of 32 cases of whom 23 had severe illness and nine normal disease. There were 63 patients in total. No obvious differences between the two groups in terms of distribution of sex, age or severity of their conditions were found.

Therapeutic regimens

The integrated treatment group received standard treatment with Western medicine plus treatment with TCM (either regimen 1, 2 or 3 according to the different syndromes and pathological stages of the illness; appropriate changes were made as the illness progressed.

The group treated with Western medicine received standard treatment alone.

Standard treatment

The standard treatment included the following components: hormone, antiviral agents, antibiotics and immunopotentiators.

Hormone: dosages were prescribed according to the severity of syndromes (80 mg, 160 mg, 320 mg or 640 mg per day in an intravenous drip).

Antivirals: 5% glucose 250 ml + canciclovir 250 mg in intravenous drip, twice per day.

Antibiotics: one treatment regime was selected from the following:

• levofloxacin 0.2 iv drip, twice per day + azithromycin 0.5 iv drip once per day (Qd)
• rocephin 2.0 iv drip per day + azithromycin 0.5 iv drip per day
• sulperazon 2.0 iv drip twice daily + azithromycin 0.5 iv drip per day


Immunopotentiator: thymopolypeptides 20 mg intravenously (in small bottle) per day

Other medications: appropriate doses of medicines to relieve fever, ease pain and repel sputum, soothe cough and asthma and suppress acid.


Therapy with traditional Chinese medicine

High-fever stage: 1 to 7 days after onset of the disease with high fever as the first and the most prominent symptom.

Treatment focused on removing heat, repelling toxin and dispelling dampness and turbidity.

Regimen 1: Fossilia Chitonis (45 g) (put in first), Rhizoma Anemarrhenae (15 g), Fructus Scutellariae (15 g), Rhizoma Atractylodis (10 g), Herba Artemisiae Annuae (15 g), Radix Paeoniae Rubra (15 g), Radix Bupleuri (10 g).

Dyspnoea and cough stage: 8 to 14 days after onset, characterized by severe dyspnoea and cough, fever and increasing shadows on lungs.

Treatment focused on relieving dampness and fever and ventilating the lungs to relieve symptoms.

Regimen 2: Fructus Scutellariae (20 g), Diosoreae gracillimae (10 g), Rhizoma Coptidis (15 g), Faeces Bombycis (10 g), Trichosanthes Kirilowii (30 g), Herba Artemisiae Annuae (15 g), Semen Coicis (30 g), Flos Inulae (10 g, wrapped), Radix Curcumae (15 g), Radix Salviae Miltiorrhizae (30 g).

Absorption stage: 15 days after onset of the disease, temperature returning to normal level, dyspnoea and cough occurring occasionally (worse after physical exertion), and the shadows in the lungs being absorbed.

Treatment focused on tonifying qi and replenishing yin, repelling phlegm, promoting blood circulation and removing dampness and turbidity.

Regimen 3: Radix Panacis Quinquefolii (45 g), Fructus Corni (30 g), Radix Astragali (30 g), Trichosanthes Kirilowii (30 g), Herba Coelogynes Punctulatae (15 g), Rhizoma Coptidis (15 g), Herba Patriniae cum Radice (30 g), umbellate pore/Poris Cocos (15 g each) and Radix Salviae Miltiorrhizae (30 g).

The above regimens were decocted regularly, 300 ml each time, taken orally in three 100 ml doses.

Evaluation indices

Traditional Chinese medicine symptoms

Semiquantitative evaluation criteria centrally developed by the researchers were adopted. The scoring system was as follows:

• none = 0 points
• slight = 1 point
• medium = 2 points
• serious = 3 points


During the course of treatment, scores were assigned once a day; statistical analyses were carried out on days 7, 14 and 21.

Routine examination of chest X-rays was done on days 1, 3, 5, 7 and 21 (additional examinations were made when there was a change in the patient’s condition). A statistical analysis was made at the end of the treatment to compare the percentage of patients whose radiographs showed absorption of shadow and those with shadow residues between the two groups. The routine blood examination included counts of leukocytes, neutrophilic granulocytes, lymphocytes and blood platelets to allow comparisons of the counts before and after treatment and between the treatment groups. The blood biochemical indices measured included creatinine kinase (CK), creatinine kinase-isoenzyme (CK-MB), lactate dehydrogenase (LDH), hydroxybutyric acid-dehydrocortisone (HBDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to allow comparisons of the values before and after treatment and between treatment groups.

Observations

Observations were recorded on the following: TCM symptoms, fever stages (temperature, time of fever abatement), lung X-ray, routine blood examination and blood biochemical indices, use of hormone, and the administration of regimens 1, 2 and 3. The observation period lasted 21 days.

Quality control

The investigators were qualified physicians who were given the necessary training. A report was made on every case participating in the study every day, the relevant case report form was filled out every day by the physician in-charge and submitted to the head of subject for examination and inspection of original data, and signature after it had been verified. The herbal pieces used conformed to the standards of the Chinese Pharmacopoeia (2000 Edition, Volume I).

Data management and statistical treatment

The data on each participant were faxed to the clean area every day. Upon completion of observations on all the 63 cases, the Department of Science and Education in the Oriental Hospital established the database. After the test for normality and the homogeneity test for variance had been carried out the t-test was applied to the interblock mean and a X2 test to rate comparison.

Results

Changes of general concomitant syndromes (total value of symptoms) over three weeks

The results of the analysis of general changes in symptoms are shown in Table 1.

Table 1. Comparison of the changes of general concomitant syndromes (general value of symptoms) over 3 weeks (mean ± standard deviation)

Treatment group

Days 1-7

Days 8-14

Days 15-21

 

mean ± SD

mean ± SD

mean ± SD

Integrated treatment (TCM plus Western medicine) (31 cases)

22.32 ± 6.09

9.79 ± 4.83*

2.08 ± 1.70*

Treatment with Western medicine (32 cases)

24.30 ± 7.60

15.74 ± 5.83

7.51 ± 4.72

 

SD, Standard deviation; TCM, Traditional Chinese medicine.
*p < 0.001.


Relative to the control group, the integrated treatment group showed a significant decline in the general value of toxicosis symptoms, especially in the second and third weeks of treatment (p < 0.001).

The integrated treatment group also showed radical improvement in alleviation of headaches, arthralgia, pantalgia, cough, expectoration and haemoptysis, chest pain, poor appetite, nausea, sweating and cardio palmus in comparison with the group treated with Western medicine.

Comparison of the absorption of pulmonary inflammation on chest radiographs

As shown in Fig. 1, after the 21-day period of treatment, 27 patients in the integrated treatment group (87.1%) and 18 patients in the group treated with Western medicine (56.3%) showed absorption of shadow. Four patients in the integrated treatment group (12.9%) and 14 (43.8%) in the group treated with Western medicine had residual inflammation. The integrated treatment resulted in better alleviation of lung inflammation than treatment with Western medicine alone at the end of the treatment period (p < 0.05).


Fig. 1. Comparison of the absorption of pulmonary inflammation on chest radiographs

Routine blood examination

Table 2 shows the changes in the results of routine blood examinations in the two treatment groups before and after treatment.

Table 2. Changes in results of routine blood examinations before and after treatment in the two treatment groups (mean ± standard deviation)

Blood parameter

Integrated treatment group

Western medicine-treated group

 

Pre-treatment

Post-treatment

Pre-treatment

Post-treatment

White blood cells (x109/l)

6.46 ± 3.58

9.82 ± 3.29**

7.29 ± 2.87

10.51 ± 3.85 • •

Neutrophils (%)

78.16 ± 14.31

80.19 ± 17.80*

79.71 ± 11.57

83.84 ± 7.33 •

Lymphocytes (%)

15.41 ± 11.73

15.42 ± 16.33

15.68 ± 10.34

12.21 ± 8.39

Platelet count (x109/l)

161.44 ± 61.76

186.00 ± 75.36

187.46 ± 101.85

174.33 ± 70.07

 

The difference in the white blood cell count of the integrated treatment group before and after treatment was ** p < 0.001, neutrophil (%) *p < 0.05.

The difference in the white blood cell count of the control group before and after treatment was • • p < 0.001, neutrophil (%) • p < 0.05.


There was no statistically significant difference between the two groups either before or after the treatment.

Changes in blood biochemistry

The changes in the blood biochemistry in the two treatment groups before and after treatment are summarized in Table 3.

Table 3. Changes in blood biochemistry before and after treatment

Item measured

Integrated treatment group

Western medicine-treated group

 

Pre-treatment

Post-treatment

Pre-treatment

Post-treatment

CK (U/l)

163.7 ± 140.33

64.00 ± 66.92

152.17 ± 187.32

96.33 ± 121.81

CK-MB

39.64 ± 33.97

26.71 ± 7.97

35.11 ± 23.22

28.56 ± 9.91

LDH (U/l)

274.29 ± 119.85

174.45 ± 38.34*

248.33 ± 185.93

203.6 ± 97.46

HBDH

148.75 ± 50.55

137.25 ± 35.14

283.60 ± 154.67

227.6 ± 105.95

ALT (IU/l)

100.79 ± 85.68

91.38 ± 55.38

69.36 ± 94.16

71.16 ± 54.80

AST (IU/l)

53.85 ± 39.95

24.23 ± 7.76**

58.37 ±41.72

29.25 ± 17.73 •

 

CK, Creatinine kinase; CK-MB; LDH, lactate dehydrogenase; HBDH; ALT, alanine aminotransferase; AST, aspartate aminotransferase.

The difference in LDH of the integrated treatment group before and after the treatment was *p < 0.05, AST **p < 0.05.

The difference of AST of the control group before and after treatment was •p < 0.05.


There was no statistically significant difference between the two groups either before or after the treatment.

Of the 63 study participants, seven died (11.1%). Of the 31 patients in the integrated treatment group, three died (9.67%); average age 53.33 years. One of these patients had hypertension with complications and one had coronary heart disease. Of the 32 patients in the group treated with Western medicine, four patients died (12.5%); average age was 55.5 years. One patient had hypertension with complications and one had type-2 diabetes.

Conclusion and discussion

SARS can be categorized as an epidemic febrile disease on the basis of TCM theory. It is caused by exogenous pathogens that trigger the inner pathogens. There is characteristically a sudden and fierce outbreak and rapid spread. With the aggravating toxicosis and inner dampness, high fever is usually the first and most prominent symptom, rapidly followed by lung or visceral damage resulting in cough and breathing difficulties. In some patients the condition worsened further giving rise to fever in yin and blood and over-consumption of the yin of liver and kidney, which was manifested by cyanosis, purple tongue and decreased oxygen saturation. In serious cases, patients died from sudden failure of the heart-yang. Death was caused by direct damage to visceral organs in some severe cases. Taking a comprehensive view of the onset, development process and main clinical features of SARS, it can be concluded that the treatment should be administered in a timely manner; most importantly in the early stage. The therapeutic approach should be focused on relieving fever and toxin, dispelling inner dampness and turbidity, reinvigorating qi and improving yin. The therapeutic regimen comprises several different phases appropriate to the stage of development of the disease and a series of regimens should be administered in large dosages.

Therefore, we propose that the treatment should be divided into three stages.

High-fever stage: 1-7 days after onset of the disease, when high fever and a thick yellow tongue coating are prominent features. The treatment at this stage should focus on eliminating the fever and toxin and removing the inner dampness and turbid pathogens through administration of SARS regimen 1.

Dyspnoea and cough stage: 8-14 days after onset of the disease, when the affliction develops rather fast and patients suffer from breathing difficulty and fever which should be controlled. The shadow over the lung is expanding during this stage. The treatment should focus on removing the internal dampness and ventilating lung to relieve symptoms through administration of SARS regimen 2.

Absorption stage: 15 days after onset of the disease, when the fever can be sensed by the patient, difficulty in breathing occurs occasionally, especially after physical exertion, the tongue has a red or reddish colour, and the shadows over the lungs begin to shrink gradually. The therapeutics should focus on tonifying qi and replenishing yin, reducing phlegm, promoting blood circulation, and removing internal dampness and turbidity through administration of SARS regimen 3.


The results of this study indicate that prescriptions 1, 2 and 3 can effectively alleviate symptoms of general toxicosis caused by fever, especially in the second and third weeks after the onset of disease. Radical alleviation of headaches, arthralgia, myalgia, cough, and hemoptysis, chest pain, poor appetite, nausea, sweating, and cardio palmus were observed. The alleviation of lung inflammation was clearly better in the integrated treatment group than in the group treated with Western medicine alone. At the end of the treatment, there were more patients whose lung shadows had shrunk in the group treated with integrated TCM and Western medicine than in the group treated with Western medicine alone.

In conclusion, the integrated therapy with TCM and Western medicine can be effective in treatment of SARS and has no obvious side-effects. Further research on TCM is planned in the areas of recovery therapy and recuperation nutrition.

Acknowledgements

The research was supported by a special fund from the State Administration of Traditional Chinese medicine. We are indebted to Mr Wang Yongyan, of the Chinese Academy of Sciences, Professor Zhang Boli, Professor Sun Sulun, Professor Jiang Liangduo and Professor Zhou Ping’an for their help and instruction starting from the establishment of the project through to its implementation. We are also grateful to the leaders of the State Administration of Traditional Chinese Medicine, Beijing Traditional Chinese Medicine University, Fengtai District Bureau of Health, and the Oriental Hospital for their support.

Bibliography

1. Beijing SARS Treatment and Command Centre. Clinical guide to SARS treatment. Beijing, China Centre for Disease Prevention and Control, 2003.

2. Traditional Chinese medicine regimen for SARS prevention and treatment (trial version). Beijing, State Administration of Traditional Chinese Medicine, 2003.

3. Traditional Chinese medicine regimen for SARS prevention and treatment. Beijing, Beijing Administration of Traditional Chinese Medicine, 2003.

 

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