Effectiveness of ECP Therapy in Stable Angina Pectoris Patients

Angina Pectoris Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04873687
• Other study ID #: Card-202103.01
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2023
• Est. completion date: December 2026

Study information

• Verified date: September 2023
• Source: Universitas Padjadjaran
• Contact: Mohammad R Akbar, MD, FIHA.
• Phone: +6281221040265
• Email: m.r.akbar[@]unpad.ac.id
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: December 2026
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Angina Pectoris
• Angina, Stable
• Counterpulsation

Intervention

Device:
• External Counter Pulsation (ECP) therapy
ECP therapy consist of 36 session, each session @1 hour/day, five days a week with initial pressure of 300mmHg

Locations

Country	Name	City	State
Indonesia	Dr. Hasan Sadikin General Hospital	Bandung	West Java

Sponsors (1)

Lead Sponsor	Collaborator
Universitas Padjadjaran

Country where clinical trial is conducted

Indonesia, 

References & Publications (6)

Arora RR, Chou TM, Jain D, Fleishman B, Crawford L, McKiernan T, Nesto RW. The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes. J Am Coll Cardiol. 1999 Jun;33(7):1833-40. doi: 10.1016/s0735-1097(99)00140-0. — View Citation

Head SJ, da Costa BR, Beumer B, Stefanini GG, Alfonso F, Clemmensen PM, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Kappetein AP, Kastrati A, Knuuti J, Kolh P, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A, Windecker S, Juni P, Sousa-Uva M. Adverse events while awaiting myocardial revascularization: a systematic review and meta-analysis. Eur J Cardiothorac Surg. 2017 Aug 1;52(2):206-217. doi: 10.1093/ejcts/ezx115. — View Citation

Rampengan SH, Prihartono J, Siagian M, Immanuel S. The Effect of Enhanced External Counterpulsation Therapy and Improvement of Functional Capacity in Chronic Heart Failure patients: a Randomized Clinical Trial. Acta Med Indones. 2015 Oct;47(4):275-82. — View Citation

Subramanian R, Nayar S, Meyyappan C, Ganesh N, Chandrakasu A, Nayar PG. Effect of Enhanced External Counter Pulsation Treatment on Aortic Blood Pressure, Arterial Stiffness and Ejection Fraction in Patients with Coronary Artery Disease. J Clin Diagn Res. 2016 Oct;10(10):OC30-OC34. doi: 10.7860/JCDR/2016/23122.8743. Epub 2016 Oct 1. — View Citation

Wu E, Desta L, Brostrom A, Martensson J. Effectiveness of Enhanced External Counterpulsation Treatment on Symptom Burden, Medication Profile, Physical Capacity, Cardiac Anxiety, and Health-Related Quality of Life in Patients With Refractory Angina Pectoris. J Cardiovasc Nurs. 2020 Jul/Aug;35(4):375-385. doi: 10.1097/JCN.0000000000000638. — View Citation

Zhang C, Liu X, Wang X, Wang Q, Zhang Y, Ge Z. Efficacy of Enhanced External Counterpulsation in Patients With Chronic Refractory Angina on Canadian Cardiovascular Society (CCS) Angina Class: An Updated Meta-Analysis. Medicine (Baltimore). 2015 Nov;94(47):e2002. doi: 10.1097/MD.0000000000002002. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	Myocardial Micro-alternation Index (MMI)	Myocardial Micro-alternation Index is part of ECG dispersion mapping (ECG-DM)	At baseline and week 7 (post intervention)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Major Adverse Cardiac Event (MACE)	Number of incidence of Major adverse cardiac event	2 years
Secondary	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)

External Links

•   Indonesian Heart Association Guidelines for External Counterpulsation Therapy for Patients with Cardiovascular Disease