Effectiveness of ECP Therapy in Stable Angina Pectoris Patients

Study Overview
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Brief Summary
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External Counterpulsation (ECP) is a non-invasive therapy using pressured cuff that is performed on patients with refractory stable angina pectoris to relieve symptoms and increase quality of life. In Indonesia, waiting time for getting coronary artery bypass grafting (CABG) procedure for revascularization treatment in stable angina pectoris patients is way longer than international recommendation which correlates with increase morbidity and mortality during the waiting time. Utilization of ECP for such patients who wait for CABG procedure is still unclear. The investigator aim to evaluate efficacy of addition of ECP compared with medical therapy alone for this population. The efficacy is evaluated using measurement from echocardiography result, treadmill test result, and clinical outcome. if applicable, examination of myocardial perfusion using nuclear examination will also be performed.

Detailed Description
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Waiting time for elective CABG procedure in Indonesia is usually longer than six weeks, way longer than the European society of cardiology recommendation. During the waiting time, patients still complain of having troubling chest pain and at risk from 1.7% mortality even after optimal medical therapy. ECP is a non-invasive therapy using a pressured cuff performed on patients that have been utilized in refractory angina pectoris patients to relieve symptoms, increase the quality of life, and decrease future major adverse cardiac events (MACE). This study is proof of principal clinical trial to evaluate the efficacy of addition ECP therapy after optimal medical therapy for stable angina pectoris patients waiting for CABG in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. Eligible patients will be informed about the study and randomized to the intervention arm. Patients in the experimental arm will undergo ECP therapy consisting of 36 sessions, each session @1 hour/day, five days a week with an initial pressure of 300mmHg. No intervention will be given to patients in the control arm. The primary and secondary endpoint is the change in variables measured before and after the intervention is fully implemented. The primary endpoint variables are global longitudinal strain (GLS), Left ventricular ejection fraction (LVEF), Time to ST-Segment depression, duration of treadmill test, the Canadian cardiovascular society (CCS) score, and the Seattle angina questionnaire (SAQ) score. The secondary endpoint variable will be myocardial perfusion score measured as Summed Rest Score, Summed Stress Score, Summed Difference Score, Myocardial Micro-alternation Index (MMI), the level of Vascular Endothelial Growth Factor (VEGF), microRNA-92a (miR-92a), NT pro BNP, Troponin, incidence of MACE, general quality of life based on questionnaire The Indonesian EQ-5D-5L, and effectiveness of ECP for stable angina pectoris patients with pharmaco-economy studies. This change will then be compared between the intervention experimental arm and control arm. Safety oversight by a Data and Safety Monitoring Board (DSMB) will be conducted by independent parties. Internal Data Monitoring Committee (DMC) will be established to oversee the study, focused on data quality. Quality control (QC) procedures will be implemented beginning with the data entry system. Data QC checks that will be run on the database will be automatically generated weekly, and any quality issues identified will be reviewed by the DMC a plan put in place for resolution.

Official Title
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Effectiveness of External Counter Pulsation (ECP) Therapy in Stable Angina Pectoris Patients; a Proof of Principal Clinical Trial

Conditions
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Counterpulsation, Angina Pectoris

Intervention / Treatment
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* Device: External Counter Pulsation (ECP) therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years old Diagnosed with stable angina pectoris Anatomic vessel disease (VD) lesion with 2VD/3VD Indicated for CABG and in waiting list of CABG procedure; or refuse for CABG and choose medical therapy only; or patients who are decided by the responsible doctor for medical treatment alone because of the high risks of CABG surgery. Not planned to urgent CABG Minimum optimal medical therapy within 2 weeks Able and willing to sign informed consent and comply with study procedures The patient lives in Bandung City and its neighborhood Retired patient; or not actively working during working hours; or willing to take the time to participate in research. Exclusion Criteria: Congestive Heart Failure Chronic heart failure with Functional Class NYHA III - IV LVEF <35% Unprotected left main stenosis >50% Blood pressure >180/110mmHg Acute coronary syndrome Acute Heart Failure Severe aorta regurgitation Malignant arrhythmia Atrial fibrillation Premature ventricular complex Peripheral occlusive artery disease Phlebitis Deep vein thrombosis Hemorrhagic diathesis Severe chronic kidney disease Aortic aneurysm Abdominal aneurysm Osteoarthritis Low back pain Pregnancy Registered as other clinical study participant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The intervention will be administered to eligible stable angina pectoris patients Dr. Hasan Sadikin General Hospital in a randomized manner neither of experiment or control group.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>The intervention arm will comprise study participants who receive intervention therapy (i.e eligible stable angina pectoris patients in intervention arm who agree to participate) | Device: External Counter Pulsation (ECP) therapy<br>* ECP therapy consist of 36 session, each session @1 hour/day, five days a week with initial pressure of 300mmHg<br>|
| No Intervention: Control<br>Eligible stable angina pectoris patients in the control arm will receive no intervention therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Global Longitudinal Strain (GLS) | GLS is a parameter captured through transthoracic echocardiography. GLS was calculated as the mean peak longitudinal systolic strain of all the LV segments, consistent with American Society of Echocardiography (ASE) guidelines. | At baseline and week 7 (post intervention) | 
| Change in Left Ventricular Ejection Fraction (LVEF) | LVEF is a parameter captured through transthoracic echocardiography. LVEF was calculated by Simpson biplane method | At baseline and week 7 (post intervention) | 
| Change in Time to mm ST-segment Depression | Time to induce significant ST-segment Depression using treadmill exercise test | At baseline and week 7 (post intervention) | 
| Change in Duration of Treadmill Test | Maximally tolerated time of treadmill exercise test using Bruce protocol or Modified Bruce protocol | At baseline and week 7 (post intervention) | 
| Change in CCS score | Degree of presenting chest pain symptoms using the Canadian cardiovascular society (CCS) class score. CCS class score ranging from 1 (mild) to 4 (severe) | At baseline and week 7 (post intervention) | 
| Change in Seattle Angina Questionnaire (SAQ) Score | Quality of life based on The Seattle Angina Questionnaire measurement. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life. A change of 10 points in any of the subscales is considered to be clinically important. | At baseline and week 7 (post intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Summed Rest Score (SRS) | Summed Rest Score is part of myocardial perfusion parameters of SPECT myocardial perfusion defects examination. The score are accumulated from 17 polar map segment. each segment scored. the extent and severity of perfusion deficits while rest ranging from 0 to 4 with higher score mean worse clinical apperance. | At baseline and week 7 (post intervention) | 
| Change in Summed Stress Score (SSS) | Summed Stress Score is part of myocardial perfusion parameters of SPECT myocardial perfusion defects examination. The score are accumulated from 17 polar map segment. each segment scored. the extent and severity of perfusion deficits while stress ranging from 0 to 4 with higher score mean worse clinical apperance. | At baseline and week 7 (post intervention) | 
| Change in Summed Difference Score (SDS) | Summed Difference Score is part of myocardial perfusion parameters of SPECT myocardial perfusion defects examination. SDS can be calculated by subtracting the SRS from the SSS (SDS = SSS - SRS). This measure is used to describe the degree to which the deficit/ischemia is reversible. An SDS score of 0-1 indicates no ischemia; 2-4 points indicate mild ischemia; 5-6 points indicate moderate ischemia; while 7 or more points indicate severe ischemia. | At baseline and week 7 (post intervention) | 
| Myocardial Micro-alternation Index (MMI) | Myocardial Micro-alternation Index is part of ECG dispersion mapping (ECG-DM) | At baseline and week 7 (post intervention) | 
| The level of Vascular Endothelial Growth Factor (VEGF) | Blood tests were carried out to determine levels of VEGF using ELISA and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The measurement unit is pg/ml. | At baseline and week 7 (post intervention) | 
| The level of microRNA-92a (miR-92a) | Blood tests were carried out to determine levels of miR-92a using ELISA and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). | At baseline and week 7 (post intervention) | 
| The level of NT pro BNP and Troponin | Blood tests were carried out to determine levels of NT pro BNP (measurement unit pg/ml). | At baseline and week 7 (post intervention) | 
| The level of Troponin | Blood tests were carried out to determine levels of Troponin (measurement unit ng/ml). | At baseline and week 7 (post intervention) | 
| Change in Quality of Life | Quality of life based on Questionnaire The Indonesian EQ-5D-5L, is a questionnaire used to assess the quality of life of angina pectoris patients undergoing ECP treatment, allowing us to determine how much money can be saved in extending a patient's life for one year. It consists of five assessment domains, which are walking ability, self-care, usual activities, pain/discomfort, and anxiety/depression. The normal range is 0-1, with a score of 1 indicating the best quality of life. | At baseline and week 7 (post intervention) | 
| Major Adverse Cardiac Event (MACE) | Number of incidence of Major adverse cardiac event | 2 years | 
| Effectiveness of ECP for stable angina pectoris patients | Effectiveness of ECP for stable angina pectoris patients is based on pharmacoeconomics. The assessment will use the ICER formula, comparing optimal medication therapy from both healthcare and national insurance perspectives, taking into account about nominal outcomes, clinical outcomes, and patient quality of life outcomes. The results from the formula will then be input into a diagram to determine whether they fall into quadrant 1, 2, 3, or 4 (the best outcome is if it falls into quadrant 2). | At baseline and week 7 (post intervention) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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External Counterpulsation, Stable Angina Pectoris, Indicated CABG, Global longitudinal strain, Ischemic response