CoROnary SinuS Reducer implantatiOn for ischemiA reDuction

Refractory Angina Pectoris Clinical Trial

— CrossRoad  

Official title:

The Influence of Coronary Sinus Reducer Implantation on Exertional Capacity, Extent of Myocardial Ischemia and hrECG Markers of Arrhythmogenicity in Patients With Refractory Angina Pectoris

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04121845
• Other study ID #: CrossRoad
• Status: Completed
• Phase: N/A
• Start date: January 1, 2019
• Est. completion date: June 30, 2022

Study information

• Verified date: July 2022
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with refractory angina pectoris have low quality of life and reduced exertional capacity. Studies have shown that the coronary sinus reducer (CSR) implantation improves the quality of life. However, to date there are no firm objective data on improvement of exertional capacity. Studies have shown a large influence of placebo effect after interventional procedures, which is even more pronounced than in medically treated patients. As angina pectoris presents entirely subjective perception of chest discomfort, its improvement may be influenced by this effect in up to 30 %. The investigators will study weather the CSR implantation improves aerobic exertional capacity in comparison to optimal medical therapy alone. Further, the investigators will explore the extent of myocardial reversible ischemia reduction and possible influence on hrECG markers of left ventricular arrhythmogenicity. 40 patients with refractory angina CCS class (Canadian cardiovascular society) II-IV and confirmed reversible ischemia will be included. Patients will be randomized into two groups. The first group will undergo CSR implantation procedure. The second group will present a sham control group with placebo procedure. At inclusion and after 6 months the investigators will perform cardiopulmonary exercise test (CPET), single photon emission tomography for detection of reversible ischemia (SPECT), high resolution ECG (hrECG), echocardiography and asses the subjective burden of angina according to CCS score and the quality of life according to the Seattle angina Questionnaire (SAQ).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 30, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• angina pectoris CCS class II-IV

• receiving optimal medical therapy for at least one month

• confirmed reversible myocardial ischemia in left anterior descending coronary artery (LAD) and/or left circumflex coronary artery (LCX) territory by SPECT

• not candidate for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)

Exclusion Criteria:

• recent non stable angina pectoris (within 1 months)

• recent acute coronary syndrome (within 3 months)

• recent successful PCI and/or CABG (within 6 months)

• decompensated heart failure and/or recent (within 3 months) hospitalization due to heart failure

• severe heart valve(s) disease

• advanced chronic obstructive pulmonary disease (COPD) or poorly managed asthma

• peripheral arterial disease, musculoskeletal disorder or central nervous system disease which preclude exercise testing

Related Conditions & MeSH terms

• Angina Pectoris
• Ischemia
• Refractory Angina Pectoris

Intervention

Device:
• Coronary Sinus Reducer device
Coronary sinus reducer device (Neovasc, Richomnd, Canada) implantation in the coronary sinus. The procedure is performed in the cardiac catheterization laboratory through right internal jugular vein.

Other:
• Sham procedure
Puncture of the right internal jugular vein and simulation of the CSR implantation procedure.

Locations

Country	Name	City	State
Slovenia	University Medical Centre Ljubljana	Ljubljana

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana

Country where clinical trial is conducted

Slovenia, 

References & Publications (13)

Abawi M, Nijhoff F, Stella PR, Voskuil M, Benedetto D, Doevendans PA, Agostoni P. Safety and efficacy of a device to narrow the coronary sinus for the treatment of refractory angina: A single-centre real-world experience. Neth Heart J. 2016 Sep;24(9):544-51. doi: 10.1007/s12471-016-0862-2. — View Citation

Baldetti L, Colombo A, Banai S, Latib A, Esposito A, Palmisano A, Giannini F. Coronary sinus Reducer non-responders: insights and perspectives. EuroIntervention. 2018 Feb 20;13(14):1667-1669. doi: 10.4244/EIJ-D-17-00626. — View Citation

Banai S, Ben Muvhar S, Parikh KH, Medina A, Sievert H, Seth A, Tsehori J, Paz Y, Sheinfeld A, Keren G. Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris: a prospective, open-label, multicenter, safety feasibility first-in-man study. J Am Coll Cardiol. 2007 May 1;49(17):1783-9. — View Citation

De Maria GL, Kassimis G, Raina T, Banning AP. Reconsidering the back door approach by targeting the coronary sinus in ischaemic heart disease. Heart. 2016 Aug 15;102(16):1263-9. doi: 10.1136/heartjnl-2016-309642. Epub 2016 Jun 10. Review. — View Citation

Giannini F, Aurelio A, Jabbour RJ, Ferri L, Colombo A, Latib A. The coronary sinus reducer: clinical evidence and technical aspects. Expert Rev Cardiovasc Ther. 2017 Jan;15(1):47-58. Review. — View Citation

Henry TD, Satran D, Hodges JS, Johnson RK, Poulose AK, Campbell AR, Garberich RF, Bart BA, Olson RE, Boisjolie CR, Harvey KL, Arndt TL, Traverse JH. Long-term survival in patients with refractory angina. Eur Heart J. 2013 Sep;34(34):2683-8. doi: 10.1093/eurheartj/eht165. Epub 2013 May 12. — View Citation

Konigstein M, Meyten N, Verheye S, Schwartz M, Banai S. Transcatheter treatment for refractory angina with the Coronary Sinus Reducer. EuroIntervention. 2014 Feb;9(10):1158-64. doi: 10.4244/EIJV9I10A196. — View Citation

Konigstein M, Verheye S, Jolicœur EM, Banai S. Narrowing of the Coronary Sinus: A Device-Based Therapy for Persistent Angina Pectoris. Cardiol Rev. 2016 Sep-Oct;24(5):238-43. doi: 10.1097/CRD.0000000000000101. Review. — View Citation

Kralios AC, Anderson FL, Kralios FA. Protective effect of coronary sinus obstruction from primary ischemia-induced ventricular fibrillation in the dog. Am Heart J. 1993 Apr;125(4):987-95. — View Citation

Kralios AC, Nappi JM, Tsagaris TJ, Kralios FA, Kuida H. Paradoxical increase of ventricular fibrillation threshold in response to coronary sinus obstruction. Am Heart J. 1988 Feb;115(2):334-40. — View Citation

Mannheimer C, Camici P, Chester MR, Collins A, DeJongste M, Eliasson T, Follath F, Hellemans I, Herlitz J, Lüscher T, Pasic M, Thelle D. The problem of chronic refractory angina; report from the ESC Joint Study Group on the Treatment of Refractory Angina. Eur Heart J. 2002 Mar;23(5):355-70. Review. — View Citation

Myers J, Froelicher VF. Optimizing the exercise test for pharmacological investigations. Circulation. 1990 Nov;82(5):1839-46. Review. — View Citation

Verheye S, Jolicœur EM, Behan MW, Pettersson T, Sainsbury P, Hill J, Vrolix M, Agostoni P, Engstrom T, Labinaz M, de Silva R, Schwartz M, Meyten N, Uren NG, Doucet S, Tanguay JF, Lindsay S, Henry TD, White CJ, Edelman ER, Banai S. Efficacy of a device to narrow the coronary sinus in refractory angina. N Engl J Med. 2015 Feb 5;372(6):519-27. doi: 10.1056/NEJMoa1402556. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Influence of CSR implantation on echocardiographically assessed left ventricular elastance.		6 months
Other	Influence of CSR implantation on diastolic strain.		6 months
Primary	Impact of CSR versus placebo procedure on exertional capacity measured by maximal oxygen consumption (VO2) during cardio-pulmonary exercise testing.	Maximal oxygen consumption on cycle spiroergometry using the same ramp exercise protocol during the same part of the day.	6 months
Secondary	Impact of CSR versus placebo procedure on exercise duration time during cardio-pulmonary exercise testing.	Exercise duration time on cycle spiroergometry using the same continuous exercise protocol during the same part of the day.	6 months
Secondary	Change in the extent of myocardial reversible ischemia calculated by single-photon emission computed tomography (dynamic scintigraphy).	Dynamic myocardial scintigraphy with the use of a 4 segment model of the left ventricle for calculation of absolute regional perfusion (ml/g/min) during rest and during pharmacologic stress. Change in the extent of myocardial reversible ischemia calculated by single-photon emission computed tomography.	6 months
Secondary	Change in the extent of myocardial reversible ischemia calculated by single-photon emission computed tomography (static scintigraphy).	Static myocardial scintigraphy with the use of a 17 segment model for the relative calculation of regional perfusion during rest and pharmacologic stress.	6 months
Secondary	Change in RR interval variability as assessed by hrECG.	5 min recording of hrECG (1000 Hz) for the calculation of RR interval variability.	6 months
Secondary	Change in late potentials as assessed by hrECG.	5 min recording of hrECG (1000 Hz) for the calculation of late potentials.	6 months
Secondary	Change in QT variability as assessed by hrECG.	5 min recording of hrECG (1000 Hz) for determination of QT variability.	6 months
Secondary	Change in Canadian Cardiovascular Society angina pectoris class (CCS).	Change in CCS class I-IV. Acco	3 months, 6 months
Secondary	Impact of CSR versus placebo procedure on quality of life according to Seattle angina questionnaire (SAQ).	Change in each of the five categories: Physical Limitation Scale (range 1-100), Anginal Stability Scale (range 1-100), Anginal Frequency Scale (range 1-100), Treatment Satisfaction Scale (range 1-100), Disease Perception Scale (range 1-100). Higher values in scale represent better outcome. Subscales are not combined.	3 months, 6 months