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Trial registered on ANZCTR


Registration number
ACTRN12613000905763
Ethics application status
Approved
Date submitted
6/08/2013
Date registered
14/08/2013
Date last updated
14/08/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomized, double-blind, placebo-controlled clinical trial of Shen Mi Tang in Treating subacute cough
Scientific title
In patients with post infectious cough of 3-8 weeks, does Shen Mi Tang compared to placebo, improve cough?
Secondary ID [1] 282987 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
post infectious cough 289814 0
Condition category
Condition code
Respiratory 290163 290163 0 0
Other respiratory disorders / diseases
Alternative and Complementary Medicine 290164 290164 0 0
Herbal remedies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be a randomized, placebo-controlled, double-blind clinical trial with medication for 7 days followed by observation for 7 days also.
There were two groups in the study. The subjects of Treatment group will take Shen Mi Tang (400mg), 5 capsules three times a day(6g per day) per oral for a 7 days course of treatment.
Components of Shen Mi Tang
Ephedrae Herba 6g
Armeniacae Semen 4.8g
Magnoliae Cortex 3.6g
Auranti Nobilis Pericarpium 3g
Glycyrrhizae Radix 2.4g
Bupleuri Radix 2.4g
Perilla Herba 1.8g
These raw herbs were refined to 4g extract and mixed with 2g starch to 6g powder by Sheng Chang Pharmaceutical Co., Ltd.
dextromethorphan 15mg/TAB per oral one to three times a day will be given as rescue drug when cough is intolerable
To get cough symptom score , a phone call at day 3,5 of treatment was given to the patients by study coordinator. a card was also given to patient to record their daily drug taking and Visual Analogue Scale(VAS) of cough.
The Visual Analogue Scale(VAS) will be adopted for measuring the severity of patient reported cough.The patient will be asked to mark the severity of his/her cough condition on a visual analogous scale of 0 to 100 mm at the time points (Day 1,3,5,8,15).
Intervention code [1] 287699 0
Treatment: Drugs
Comparator / control treatment
The subjects of Control group will take placebo capsules of Shen Mi Tang, 5 capsules three times a day(6g starch per day) per oral for a 7 days course of treatment.
Control group
Placebo

Outcomes
Primary outcome [1] 290192 0
Percentage of patients with "Significant Improvement" in daytime Cough Symptom Score(CSS) will be the primary efficacy endpoint of this study.
Timepoint [1] 290192 0
"Significant Improvement" is defined as that patient's CSS score on day 8 is reduced by two or more score levels comparing with the baseline CSS on day 1.
Secondary outcome [1] 304083 0
Percentage of patients with ’’Improvement” in daytime or night-time Cough Symptom Score(CSS)
Timepoint [1] 304083 0
“Improvement” is defined as that patient’s CSS score on day 8 is reduced by one score level comparing with the baseline CSS on day 1.
Secondary outcome [2] 304119 0
Change from baseline in visual analogous scale(VAS) score on cough severity
Timepoint [2] 304119 0
a visual analogous scale of 0 to 100 mm at the time points (Day 1,3,5,8,15).

Eligibility
Key inclusion criteria
1.age from 20 to 65 y/o
2.persist cough for 3-8 weeks without present illness as asthma, Gastroesophageal reflux disease,postnasal drip)
3.Cough pattern is dry cough or cough with little sputum. presentations of cough are throat itching, paroxysmal cough or cough irritated by smoke,dust or temperature.
4.Day time or night-time Cough Symptom Score (CSS) >= 2
5.sign informed consent form
Minimum age
20 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.chronic respiratory disease as asthma, bronchiectasis
,chronic bronchitis etc.
2.severe disorders which may induce persistent cough (as:cystic fibrosis,congestive heart failure etc.)
3.Gastroesophageal reflux disease or postnasal drip detected by patient or diagnosed by doctor in recent 3 months
4.neoplasm or other significant abnormality suspected under chest X ray examination
5.recent smoker (smoking abstinence shorter than 6 months )
6.pregnant or breast feeding women
7.taking Angiotension-converting enzyme inhibitors in 1 month
8.body temperature over 37.5 degrees Celsius
9.blood WBC >10000 per microliter or < 4000 per microliter
10.difficult to fit in with study process
11.other clinical trial participants in recent 1 month

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Promotional posters about the study, referral criteria and contact number of primary investigator and study coordinator were pasted on bulletin board outside clinic rooms of investigators, including two internal medical physician of traditional Chinese medicine, one chest specialist and one ENT specialist.
Patients with cough as chief complaint will be candidates and be diagnosed on the basis of detailed history and clinical examination and be referred to study coordinator by investigator if they match inclusion criteria. Trained study coordinator is responsible for enrolment of patients, study explanation, data collection. These patients will be enrolled if they fulfill the study’s eligibility criteria. The enrolled patients will be administered with study drug by the investigator and be given patient daily diary by study coordinator. Patients not fulfilling the criteria will accept other treatment administered by investigator.
Allocation concealment procedure was performed by Sheng Chang Pharmaceutical Co.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random allocation was made in blocks to keep the sizes of treatment groups similar. It was performed by Sheng Chang Pharmaceutical Co. which was entrusted with production of study drugs. However, the real content of allocation was concealed in envelope and kept by study pharmacist
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Sample size determination
According to reports of Shen Mi Tang ‘s clinical trials and our clinical observation, the response rate (p1) is about 0.6. We also suppose the placebo effect (p2) is 0.1.
Using test for Superiority, a two sided test, 5% significance level test (alpha=0.05) with power 80% power (beta =0.2), p1=0.6, p2=0.1, drop-out rate = 0.05.
Number obtained is 16 for each group under calculation by formula.
All analysis will be done on intention to treat basis.
Efficacy endpoints will be listed and summarized as appropriate: mean/median,standard deviation, minimum, maximum and total numbers for normally distributed data; median and range for non-normally distributed data; frequencies, total numbers and percentages for categorical data.
The baseline demographic characteristics in both treatment and control groups will be compared using Chi-square test or Fisher's exact test for categorical variables and t-test or Wilcoxon Rank-Sum test for continuous variables.
The percentage of patients with "Significant Improvement" and "Improvement" in daytime Cough Symptom Score will be tested using Fisher's exact test or Chi-square test. Logistic regression will be adopted to test the efficacy endpoint, if significant difference is observed in demographic variables.
Paired t-test will be used to evaluate the change from baseline in VAS score within each treatment group and un-paired t-test will be used to compare the change from baseline in VAS score between the two treatment groups. Wilcoxon signed-rank test and Wilcoxon rank-sum test will be used instead if the normal assumption is violated. The analysis of covariance (ANCOVA) may be used to account for any potential covariate such as baseline and demographic variables when comparing the difference in efficacy endpoints between the treatment group and the control group.
All efficacy tests will be conducted at an alpha level of 0.05 (2-tailed) and 95% confidence interval will be reported.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 5283 0
Taiwan, Province Of China
State/province [1] 5283 0
Taoyuan

Funding & Sponsors
Funding source category [1] 287757 0
Government body
Name [1] 287757 0
Ministry of Health and Welfare Department of Chinese Medicine and Pharmacy
Address [1] 287757 0
No.36, Tacheng St., Datong District, Taipei City 10341, Taiwan (R.O.C.)
Country [1] 287757 0
Taiwan, Province Of China
Primary sponsor type
Individual
Name
Jong-Jen Kuo (Principal investigator)
Address
Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, No. 123,Dinghu Road, Guei-shan, Taoyuan 33378, Taiwan
Country
Taiwan, Province Of China
Secondary sponsor category [1] 286479 0
Hospital
Name [1] 286479 0
Clinical Trial Center for Traditional Chinese Medicine in Chang Gung Medical Foundation
Address [1] 286479 0
No.123, Dinghu Rd., Guishan Town Ownship, Taoyuan County 333,Taiwan, R.O.C
Country [1] 286479 0
Taiwan, Province Of China

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289702 0
Chang Gung Medical Foundation Institutional Review Board
Ethics committee address [1] 289702 0
IRB, B2, No. 123,Dinghu Road, Guei-shan, Taoyuan 33378, Taiwan
Ethics committee country [1] 289702 0
Taiwan, Province Of China
Date submitted for ethics approval [1] 289702 0
26/11/2012
Approval date [1] 289702 0
18/04/2013
Ethics approval number [1] 289702 0
101-4441A3

Summary
Brief summary
Cough is one of the most common causes for medical consultation. Post infectious cough is one of main causes of Subacute cough. The effectiveness of Over the counter(OTC) drugs for cough are controversial. OTC drugs leading to sedation and other side effects also.
The Shen Mi Tang is commercially available herbal concentrates preparation, the indications for asthma, bronchitis. We found its good effects in the treatment of persistent dry cough post colds. So, it deserves evaluation by clinical trial.
The clinical trial will be undertaken at Chang Gung Memorial Hospital, 32 Subacute cough patients will be enrolled, 16 patients in Control group and 16 patients in Treatment group. The study will be a randomized, placebo-controlled, double-blind clinical trial with medication for 7 days followed by observation for 7 days also.The focus of the study is on the evaluation of efficacy of this formula for Subacute cough by Cough Symptom Score(CSS) and Visual Analogous Scale(VAS) and the safety of this formula will also be evaluated.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42054 0
Dr Jong-Jen Kuo
Address 42054 0
Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, No. 123,Dinghu Road, Guei-shan, Taoyuan 33378, Taiwan
Country 42054 0
Taiwan, Province Of China
Phone 42054 0
+886 3 3196200#2676 or +886 975360234
Fax 42054 0
+886 3 3294841
Email 42054 0
kjj308@gmail.com
Contact person for public queries
Name 42055 0
Dr Jong-Jen Kuo
Address 42055 0
Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, No. 123,Dinghu Road, Guei-shan, Taoyuan 33378, Taiwan
Country 42055 0
Taiwan, Province Of China
Phone 42055 0
+886 3 3196200#2676 or +886 975360234
Fax 42055 0
+886 3 3294841
Email 42055 0
kjj308@gmail.com
Contact person for scientific queries
Name 42056 0
Dr Jong-Jen Kuo
Address 42056 0
Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, No. 123,Dinghu Road, Guei-shan, Taoyuan 33378, Taiwan
Country 42056 0
Taiwan, Province Of China
Phone 42056 0
+886 3 3196200#2676 or +886 975360234
Fax 42056 0
+886 3 3294841
Email 42056 0
kjj308@gmail.com

No information has been provided regarding IPD availability
Summary results
No Results