CoROnary SinuS Reducer implantatiOn for ischemiA reDuction

NCT04121845 | Completed

• 1 other identifier: CrossRoad
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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).

Conditions

Refractory Angina Pectoris

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Impact of CSR versus placebo procedure on exercise duration time during cardio-pulmonary exercise testing.

  6 months

• Change in the extent of myocardial reversible ischemia calculated by single-photon emission computed tomography (dynamic scintigraphy).

  6 months

• Change in the extent of myocardial reversible ischemia calculated by single-photon emission computed tomography (static scintigraphy).

  6 months

• Change in RR interval variability as assessed by hrECG.

  6 months

• Change in late potentials as assessed by hrECG.

  6 months

Other Outcomes (2)

• Influence of CSR implantation on echocardiographically assessed left ventricular elastance.

  6 months

• Influence of CSR implantation on diastolic strain.

  6 months

Study Arms (2)

Treatment group

ACTIVE COMPARATOR

Coronary sinus reducer implantation through right internal jugular vein.

Device: Coronary Sinus Reducer device

Sham group

SHAM COMPARATOR

Puncture of the right internal jugular vein and simulation of the CSR implantation procedure.

Other: Sham procedure

Interventions

Coronary Sinus Reducer device 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.

Treatment group

Sham procedure OTHER

Puncture of the right internal jugular vein and simulation of the CSR implantation procedure.

Sham group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Related Publications (14)

• 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.

  PMID: 11846493 BACKGROUND

• 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.

  PMID: 23671156 BACKGROUND

• 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.

  PMID: 27935738 BACKGROUND

• 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.

  PMID: 26886464 BACKGROUND

• 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.

  PMID: 25651246 BACKGROUND

• 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.

  PMID: 24561732 BACKGROUND

• 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.

  PMID: 27299456 BACKGROUND

• 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.

  PMID: 17466229 BACKGROUND

• 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.

  PMID: 2225380 BACKGROUND

• 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.

  PMID: 3341168 BACKGROUND

• 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.

  PMID: 8465771 BACKGROUND

• 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.

  PMID: 27288281 BACKGROUND

• 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.

  PMID: 29086709 BACKGROUND

• Mrak M, Zlahtic T, Starc V, Ivanovski M, Bunc M, Zizek D. The Impact of Coronary Sinus Reducer on Arrhythmic Properties in Patients with Refractory Angina. Rev Cardiovasc Med. 2023 Dec 26;24(12):368. doi: 10.31083/j.rcm2412368. eCollection 2023 Dec.

  PMID: 39077099 DERIVED

MeSH Terms

Conditions

Angina Pectoris

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Matjaž Bunc, Prof.

  University Medical Centre Ljubljana, Slovenia

  PRINCIPAL INVESTIGATOR

• David Žižek, Assoc. Prof.

  University Medical Centre Ljubljana, Slovenia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Punction of the right internal jugular vein and CSR implantation procedure simulation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of catheterization laboratory

Study Record Dates

• First Submitted: October 6, 2019
• First Posted: October 10, 2019
• Study Start: January 1, 2019
• Primary Completion: December 31, 2021
• Study Completion: June 30, 2022
• Last Updated: July 25, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

SL (1)