The methodology of the Study is as follows: Topic of the Study: Clinical Efficacy of Vyghriharitaki in the Management of Chronic bronchitis. Clinical Trial Protocol ID: ACT-BTS-2010. Null hypothesis Vyaghriharitaki is not effective in the management of Chronic bronchitis. Alternate hypothesis Vyaghriharitaki is effective in the management of Chronic bronchitis. Plan of Study The present study was divided in two sections: 1. Conceptual study: This section consists of critical review of relevant literature available in Ayurveda, previous research works done, various modern medical textbooks and journals. 2. Clinical study: The clinical study was designed in the following pattern- Study design: Study Type : Interventional Purpose : Treatment Masking : Open label Control : Not controlled Timing : Prospective End Point : Efficacy and Safety No. of Groups : One Settings: Clinically diagnosed patients of Chronic bronchitis were selected from the Out-patient and In-patient department of Kayachikitsa, Institute for Postgraduate Teaching and Research in Ayurveda, Gujarat ayurveda University, Jamnagar, Gujarat. Source/s of monetary and material support: 1. Institute for Postgraduate Teaching and Research in Ayurveda, Gujarat Ayurveda University, Jamnagar, Gujarat. Efficacy of Vyaghriharitaki Avaleha on Chronic Bronchitis Page 40
2. The formulation, Vyaghriharitaki Leha was supplied by CCRAS, New Delhi, manufactured at Arya Vaidya Sala Factory, Kanjikode, Palakkad, Kerala, by using the ingredients and method preparation given in AFI. The clinical trial protocol and the Case Record Forms were also supplied by CCRAS. Name and Address of the Sponsor Central Council for Research in Ayurveda and Siddha (C.C.R.A.S.), Jawahar Lal Nehru Bhartiya Chikitsa Evam Homoeopathy Anusandhan Bhawan, 61-65, Institutional Area, Opposite D-Block, Janakpuri, New Delhi-110058 Under Department of AYUSH, Ministry of Health & Family Welfare, Government of India, New Delhi 110001. Eligibility/ Inclusion Criteria 1. Patients of either sex aged between 16 to 70 years. 2. Patient with history of uncomplicated Chronic Bronchitis. (Chronic Bronchitis is defined as a cough that occurs every day with sputum production that lasts for at least three months, two years in a row). 3. Patient willing and able to participate in the study for 16 weeks. Criteria for Exclusion 1. Patients suffering from Acute Bronchitis. 2. Patients having PEFR < 50% of the predicted value. 3. Other pulmonary diseases like Emphysema, Cor pulmonale, Cyanosis, Pneumonia, Asthma, Cystic fibrosis, Tuberculosis, Lung cancer etc. 4. Patients with poorly controlled Diabetes Mellitus (HbA1c > 10%) 5. Patients with poorly controlled Hypertension. (>160/100mm of hg) 6. Patients on prolonged (> 6 weeks) medication with corticosteroids, bronchodilators, mast cell stabilizers, antidepressants, anticholinergics, etc. or any other drugs that may have an influence on the outcome of the study. 7. Patients suffering from major systemic illness necessitating long term drug treatment (Rheumatoid arthritis, Tuberculosis, Psycho-Neuro-Endocrinal disorders, etc.) Efficacy of Vyaghriharitaki Avaleha on Chronic Bronchitis Page 41
8. Patients who have a past history of Atrial Fibrillation, Acute Coronary Syndrome, Myocardial Infarction, Stroke or Severe Arrhythmia in the last 6 months. 9. Symptomatic patient with clinical evidence of Heart failure. 10. Patients with concurrent serious hepatic disorder. 11. Alcoholics and/or drug abusers. 12. H/o hypersensitivity to the trial drug or any of its ingredients 13. Patients who have completed participation in any other clinical trial during the past six (06) months 14. Pregnant or lactating women 15. Any other condition which the Principal Investigator thinks may jeopardize the study. Laboratory Investigations: Haematology Haemoglobin/ T.L.C. / D.L.C./ E.S.R. Absolute Eosinophil Count Bio-chemistry Blood Sugar :Fasting Blood Urea / Serum Creatinine Serum Uric Acid S.G.O.T.(A.S.T.)/ S.G.P.T. (A.L.T.) Total protein/ S.Albumin/ S.Globulin/ A/G ratio Serum Bilirubin: Conjugated bilirubin/ Unconjugated bilirubin Serum Alkaline Phosphatase Serum IgE Sputum for AFB X-ray chest (PA View) ECG (when ever required) PEFR (Peak Expiratory Flow Rate) FEV 1 (Forced Expiratory Volume in 01 second) (Peak Flow meter Tests were done by Electronic Lung Health Meter, Brand name: PIKO-1; manufactured by nspire Health, USA) Efficacy of Vyaghriharitaki Avaleha on Chronic Bronchitis Page 42
Interventions Drug Vyaghriharitaki Leha Dose 10 gm twice daily Dosage form Avaleha Route of Administration Oral Time of Administration Twice a day before food Anupana Lukewarm Water Packing form 300 gm jar Duration of therapy 12 weeks Follow up 04 weeks Note: Patients were guided regarding Pathya/Apathya regimen by the Investigator / Principal Investigator. Ethical clearance: Ethical clearance was obtained from the Institutional Ethics Committee of the Institute for Post Graduate Teaching and Research in Ayurved, Gujarat Ayurved University, Jamnagar; vide Ref. PGT/7-A/Ethics/2010-2011/3381 dated 10/01/2011. Registration: This study is registered in Clinical Trial Registry of India (CTRI) vide CTRI/2011/11/002142. Informed Consent: An Informed written consent was obtained from all the subjects included in the clinical trial. This Informed Consent Form has two parts: i) Patient Information Sheet and ii) Certificate of Consent (Annexure 1). OUTCOMES Primary Outcome Measure Change in the clinical symptoms of chronic bronchitis. Secondary Outcome Measures Change in St. George s Respiratory Questionnaire (SGRQ) scores. Time Points The outcomes were measured after screening at baseline (BT) and at the end of 12 weeks (AT). Efficacy of Vyaghriharitaki Avaleha on Chronic Bronchitis Page 43
Withdrawal criteria: Subjects who develop acute complications or any other serious disease or develop serious adverse events to the interventions in the study period were to be withdrawn from the study and referred to competent centre. Rescue Medications: Subjects developing any serious events interim to the study were to be advised suitable rescue medications. For minor complaints regular medicines from the institution hospital was to be advised. Follow-up study: The included subjects were followed up for four weeks after withdrawal of drugs to note any recurrence of signs/ symptoms. Protocol: The details of the data collected from the enrolled subjects are as per the Case Record Form. Scoring Pattern used to assess various parameters The changes in the disease state of Chronic bronchitis were recorded and analyzed. Improvement was assessed by adopting standard method and scoring. Functional efficiency of the respiratory system (PEFR and FEV 1 ) were assessed both before and after the intervention by using Electronic Lung Health Meter (Brand name: PIKO-1; manufactured by nspire Health, USA) and functional ability is assessed with the help of the St. George s Respiratory Questionnaire every fourteen day of intervention and at the end of the follow up period. The details of the assessment criteria are given as follow. Assessment Parameters Clinical assessment was done on the basis of six chief complaints related to Chronic bronchitis (Productive cough, Dyspnoea, Wheezing, Chest pain, Sore throat and Nasal congestion). Productive cough 0 - Absence of Productive cough. 1- Presence of Productive cough. Dyspnoea 0 - Absence of Dyspnoea 1- Presence of Dyspnoea Efficacy of Vyaghriharitaki Avaleha on Chronic Bronchitis Page 44
Wheezing 0 - Absence of Wheezing 1- Presence of Wheezing Chest Pain 0 - Absence of Chest Pain 1- Presence of Chest Pain Sore Throat 0 - Absence of Sore Throat 1- Presence of Sore Throat Nasal Congestion 0 - Absence of Nasal Congestion 1- Presence of Nasal Congestion St George s Respiratory Questionnaire (SGRQ) After recording the details as per questionnaire the scores were calculated a) Symptoms Score b) Activity Score c) Impacts Score d) Total Score The difference between the total scores before and after intervention was calculated statistically. About St George s Respiratory Questionnaire The SGRQ is designed to measure health impairment in patients with asthma and COPD. It is in two parts. Part-1 produce the Symptoms score, and Part-2 produces the Activity and Impacts scores. A Total score is also produced. The SGRQ has total 17 questions with multiple answers. Part 1(Questions 1 to 8) covers the patients recollection of their symptoms over a preceding period that may range 1 month to 1 year. It is not designed to be an accurate epidemiological tool; its purpose is to assess the patient s perception of their recent respiratory problems. The original version was validated using a 12-month recall period. More recently a 1 month recall version (appropriately worded) has been validated. This has slightly weaker psychometric properties than the 12-month version Efficacy of Vyaghriharitaki Avaleha on Chronic Bronchitis Page 45
and produces a marginally lower Symptoms score and Total score. A 3-month recall period has been used very satisfactorily. In summary, the 3-month and 1-year versions provide the best properties, with no specific advantages to either. The 1-month version should only be used when the time frame of the study dictates. Part 2 (Questions 9 to 16) addresses the patients current state (i.e. how they are these days). The Activity score just measures disturbances to patient s daily physical activity. The Impacts score covers a wide range of disturbances of psychosocial function. Validation studies showed that this component relates in part to respiratory symptoms, but it also correlates quite strongly with exercise performance (6-minute walking test), breathlessness in daily life (MRC breathlessness score) and disturbances of mood (anxiety and depression). The Impacts score is, therefore, the broadest component of the questionnaires, covering the whole range of disturbances that respiratory patients experience in their lives. Excel-based scoring calculator has been used to calculate the three component scores. A total score which summarises the impact of the disease on overall health status is generated. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status (Annexure 3). Three component scores are calculated for the SGRQ: Symptoms - this component is concerned with the effect of respirator symptoms, their frequency and severity. Activity - concerned with activities that cause or are limited by breathlessness Impacts - covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease Statistical Design The data generated in the clinical study was analyzed by applying student t test using Statistical software- Sigmastat 3.5. Efficacy of Vyaghriharitaki Avaleha on Chronic Bronchitis Page 46
Level of Significance: p value of 0.001 : Statistically Highly Significant 0.002 to 0.04: Statistically Significant 0.05 : Statistically Insignificant Interpretation of Results: 25% - Unchanged 26-50% - Mild Positive Response 51-75% - Moderate Positive Response >75% - Marked Positive Response Efficacy of Vyaghriharitaki Avaleha on Chronic Bronchitis Page 47