Effect of Cardiotonic Pills on Chest Pain and Discomfort: A Multi-center Double-blind Randomized Controlled Trial.

Transcription

1 26 2 ( ) J Korean Oriental Med 2005;26(2): Effect of Cardiotonic Pills on Chest Pain and Discomfort: A Multi-center Double-blind Randomized Controlled Trial. Jang Insoo, 1) Ko Changnam, 2) Lee In, 3) Park Jung-mi, 3) Kim Sehyun, 3) Kim Sangwoo Dept. of Internal Medicine, College of Korean Medicine, Woosuk University Dept. of Internal Medicine, College of Oriental Medicine, Kyunghee University 1) Dept. of Internal Medicine, College of Oriental Medicine, Wonkwang University 2) Bundang CHA Oriental Medical Hospital, College of Medicine, Pochon-CHA University 3) Dept. of Health Science, College of Medicine, Pochon CHA University 4) Objectives : This was a double blinded, randomized, placebo-controlled clinical study for evaluation of safety and effective dose finding of Cardiotonic Pills in patients with chest pain and discomfort. Cardiotonic Pills are composed of Salviae Miltiorrhizae Radix ( ), Notoginseng Radix ( ) and Borneolum ( ). Major effects of Salviae Miltiorrhizae Radix and Notoginseng Radix are vasodilatation, sedation and analgesic action. Borneolum has an antibacterial effect, and can stimulate the central nervous system. All of these substances are oriental herbs that have been used for a long time in east Asia. Cardiotonic Pillsfi received Investigational New Drug (IND) approval from the Food and Drug Administration (FDA) in the USA and 40 million people in the world take this pill. We performed a phase IV clinical study to confirm its efficacy and safety in patients who have probable cardiogenic or psychogenic chest pain or chest stifling. Methods : This study was planned for a multi-center clinical trial including four university hospitals of oriental medicine in Korea. This was the first time to evaluate the planning treatment according to diagnosis ( ) of chest pain or chest discomfort according to oriental medical guidelines. The patients who were included in this trial were adult volunteers from 20 to 70 years old who had chest pain or chest discomfort more than twice during a recent month, and we received written consent to participate in this study from all of them. After administration of Cardiotonic Pills for 8 weeks, number of occurrences, duration, appearance and degree of chest pain or chest discomfort was observed and degree of symptoms (severity of illness, global improvement) were measured using a patient s global assessment composite scale. Results : In the patient s global assessment scale, the severity of illness of the Cardiotonic Pills group (n=25) was 14/25=0.56 but of the placebo group (n=25) was 7/25=0.28 (p-value=0.0449). This result indicates Cardiotonic Pills have a positive effect on the symptoms of chest pain and discomfort. However, the global improvement of the Cardiotonic Pills group was 23/25=0.92, and of the placebo group was 22/25=0.88 (p-value=0.6374). The total symptom score of the Cardiotonic Pills group was , and of the placebo group was (p-value=0.2285). The number of symptom events of the Cardiotonic Pills group was , and of the placebo group (n=25) was (pvalue=0.3660). We could not find any effects on the other factors examined besides the severity of illness, beyond the difference of standard deviations. Conclusions : Cardiotonic Pills significantly reduced chest pain and chest discomfort in patients. Therefore, we expect that Cardiotonic Pills will be helpful for patients with chest pain and chest discomfort not only caused by heart disease but also by other diseases. Key Words: Cardiotonic Pills, chest pain, chest discomfort, randomized controlled trial, clinical trials, herb medicine. 95

2 (302) 26 2 ( ) 1,2) (Cardiotonic Pills ) (Institutional Review Board for Clinical Research : IRB) : : : : 351 ( , omd@korea.com) Table 1. The Iinclusion and Exclusion Criteria [inclusion criteria] [exclusion criteria] (KGCP) IRB 1) (Table 1) 96

3 (303) (2) (1) (Cardiotonic Pills ) FDA (Investigational New Drug : IND) (Salvia Miltiorrhiza BGE.) 4-12) Table 2. The Contents of Cardiotonic Pills Contents Weight(mg) Salviae Miltiorrhizae Radix ( ) 17.5 Notoginseng Radix ( ) 3.4 Borneolum Syntheticum ( ) 0.2 Table 3. The Contents of Placebo Contents Weight (mg) Caramel ( ) 0.6 Polyethylene Glycol 6000 ( ) 22.5 Polyethylene Glycol 400 ( ) 0.5 Bornel ( ) 0.1 (Panax Notoginseng (BURK.) F.H. CHEN) (Dryobalanops aromatoca GAERTN. f.) Table 2 (2) (56 ) (3) Table 3 (4) 4 97

4 (304) 26 2 ( ) (stratum) (stratified randomized block design) (1) 1 1 X HCG (CBC), CPK, LDH, CK-MB, troponin T (2) patient s global assessment scale ( ) (severity of illness) (global improvement) Patient s global assessment scale 7 Table 4. patient s global assessment scale 7 Table 5 98

5 (305) 2 1 (very much improved), (much improved), (minimally improved) (improved), (no change), (minimally worse), (much worse), (very much worse) (not improved) (improvement rate). Visual Analog Scale(VAS) Wong-Baker faces pain rating scale 0-5 (vital sign) (1) 1 (D-14 : ) ID X- (2) 2 (D0 ; ) (3) 3 (D28 7 )

6 (306) 26 2 ( ) 2 (4) 4 (D ) Table (n=33) (n=34) 67 (Table 7) 8 9 (drop-out) , , (pvalue=0.2113, t- ) (n=25) (n=25) 50 Patient's global assessment scale patient's global assessment scale severity of illness 14/25=0.56 7/25=0.28 p-value=0.0449, patient's global assessment scale global improvement 23/25= /25= 0.88 p-value= (2) (p-value=0.2285, t- ) (pvalue=0.3660, t- ) 100

7 (307) (Cardiotonic Pills ) FDA IND Table ) Assessed for eligibility (n=81) Enrollment Excluded (n=14) Not meeting inclusion criteria (n=12) Refused to participate (n=2) Randomized (n=67) Allocation Allocated to intervention (n=33) Received allocated intervention (n=33) Did not receive allocated intervention; give reasons (n=0) Allocated to intervention (n=34) Received allocated intervention (n=34) Did not receive allocated intervention; give reasons (n=0) Follow-up Lost to follow-up; give reasons (n=0) Discontinued intervention; adverse event (n=3) poor medication compliance (n=2) protocol violation (n=1) consent withdrawal (n=2) Lost to follow-up; give reasons (n=0) Discontinued intervention; adverse event (n=3) poor medication compliance (n=3) protocol violation (n=0) consent withdrawal (n=3) Analysis Analysed (n=25) Excluded from analysis; give reasons (n=0) Cardiotonic Pills group Analysed (n=25) Excluded from analysis; give reasons (n=0) Placebogroup Fig. 2. Flow diagram of the progress through the phases of a randomized trial (based on CONSORT statement) 101

8 (308) 26 2 ( ) Table 4. Global Assessment Scale (Severity of illness) Table 5. Global Assessment Scale (Global improvement) IRB (KGCP) IRB 13 (n=33) (n=34) 68 (Figure 2) (n=25) (n=25) 50 Patient s global assessment scale 7 (Table 4). patient s global assessment scale (Table 5). patient s global assessment scale 14/25=0.56 7/25=0.28 (p-value =0.0449, ) 2 23/25= /25=0.88 (p-value=0.6374, ) (p-value=0.2285, t- ) 102

9 (309) Table 7. Personal Characteristics Cardiotonic Pills Placebo groups (n=33) (n=34) Age Sex (F : M) 11 : : 23 Droup-out 8 9 Per-Protocol Set Table 8. Results of Patient's Global Assessment Scale Cardiotonic Pills Placebo groups p-value Severity of illness Global improvement ( p-value=0.3660, t- ). A A B A B A A (n=33) (n=34) (n=25) (n=25)

10 (310) 26 2 ( ) patient's global assessment scale 14/25=0.56 7/25= Reference :67-81,85-99, Braunwald E. Fauci A, Kasper D, Hauser S, Longo D, Jameson J. Harrison (15th edition). USA : McGraw-Hill (2) : :400-1,419-20, :50-2,92-5, ;35(2): ;37(9): ; 33(2): ;37(10): ;20(6): ;21(8): ;22(5): ;23(7): Moher D, Schulz KF, Altman D, CONSORT Group. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. JAMA. 2001;285(15):