CoROnary SinuS Reducer implantatiOn for ischemiA reDuction (CrossRoad)

• ClinicalTrials.gov Identifier: NCT04121845
• Recruitment Status: Completed
• First Posted: October 10, 2019
• Last Update Posted: July 25, 2022
• Sponsor: University Medical Centre Ljubljana
• Information provided by (Responsible Party): Matjaž Bunc, University Medical Centre Ljubljana

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Refractory Angina Pectoris	Device: Coronary Sinus Reducer device; Other: Sham procedure	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Masking Description: Punction of the right internal jugular vein and CSR implantation procedure simulation.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 1, 2019
• Actual Primary Completion Date: December 31, 2021
• Actual Study Completion Date: June 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Treatment group; Coronary sinus reducer implantation through right internal jugular vein.	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.
Sham Comparator: Sham group; Puncture of the right internal jugular vein and simulation of the CSR implantation procedure.	Other: Sham procedure; Puncture of the right internal jugular vein and simulation of the CSR implantation procedure.

Outcome Measures

Primary Outcome Measures :

1. Impact of CSR versus placebo procedure on exertional capacity measured by maximal oxygen consumption (VO2) during cardio-pulmonary exercise testing. [ Time Frame: 6 months ]
   Maximal oxygen consumption on cycle spiroergometry using the same ramp exercise protocol during the same part of the day.

Secondary Outcome Measures :

1. Impact of CSR versus placebo procedure on exercise duration time during cardio-pulmonary exercise testing. [ Time Frame: 6 months ]
   Exercise duration time on cycle spiroergometry using the same continuous exercise protocol during the same part of the day.
2. Change in the extent of myocardial reversible ischemia calculated by single-photon emission computed tomography (dynamic scintigraphy). [ Time Frame: 6 months ]
   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.
3. Change in the extent of myocardial reversible ischemia calculated by single-photon emission computed tomography (static scintigraphy). [ Time Frame: 6 months ]
   Static myocardial scintigraphy with the use of a 17 segment model for the relative calculation of regional perfusion during rest and pharmacologic stress.
4. Change in RR interval variability as assessed by hrECG. [ Time Frame: 6 months ]
   5 min recording of hrECG (1000 Hz) for the calculation of RR interval variability.
5. Change in late potentials as assessed by hrECG. [ Time Frame: 6 months ]
   5 min recording of hrECG (1000 Hz) for the calculation of late potentials.
6. Change in QT variability as assessed by hrECG. [ Time Frame: 6 months ]
   5 min recording of hrECG (1000 Hz) for determination of QT variability.
7. Change in Canadian Cardiovascular Society angina pectoris class (CCS). [ Time Frame: 3 months, 6 months ]
   Change in CCS class I-IV. Acco
8. Impact of CSR versus placebo procedure on quality of life according to Seattle angina questionnaire (SAQ). [ Time Frame: 3 months, 6 months ]
   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.

Other Outcome Measures:

1. Influence of CSR implantation on echocardiographically assessed left ventricular elastance. [ Time Frame: 6 months ]
2. Influence of CSR implantation on diastolic strain. [ Time Frame: 6 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Slovenia

University Medical Centre Ljubljana

Ljubljana, Slovenia, 1000

Sponsors and Collaborators

University Medical Centre Ljubljana

Investigators

• Principal Investigator: Matjaž Bunc, Prof.; University Medical Centre Ljubljana, Slovenia
• Study Chair: David Žižek, Assoc. Prof.; University Medical Centre Ljubljana, Slovenia

More Information

Publications:

Mannheimer C, Camici P, Chester MR, Collins A, DeJongste M, Eliasson T, Follath F, Hellemans I, Herlitz J, Luscher 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. doi: 10.1053/euhj.2001.2706. No abstract available.

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.

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. doi: 10.1080/14779072.2017.1270755.

Konigstein M, Verheye S, Jolicoeur 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.

Verheye S, Jolicoeur 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.

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.

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.

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. doi: 10.1016/j.jacc.2007.01.061.

Myers J, Froelicher VF. Optimizing the exercise test for pharmacological investigations. Circulation. 1990 Nov;82(5):1839-46. doi: 10.1161/01.cir.82.5.1839.

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. doi: 10.1016/0002-8703(88)90479-6.

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. doi: 10.1016/0002-8703(93)90105-i.

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.

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.

• Responsible Party: Matjaž Bunc, Head of catheterization laboratory, University Medical Centre Ljubljana
• ClinicalTrials.gov Identifier: NCT04121845
• Other Study ID Numbers: CrossRoad
• First Posted: October 10, 2019
• Last Update Posted: July 25, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All IPD that underlie results in a publication All IPD on special request
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: After study completion and results publication. Not limited.
• Access Criteria: All IPD that underlie results in a publication on editor/researcher request. All IPD on special request.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Matjaž Bunc, University Medical Centre Ljubljana:

angina pectoris; coronary sinus reducer; quality of life; reversible ischemia; exercise testing; oxygen consumption

Additional relevant MeSH terms:

Angina Pectoris; Ischemia; Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations