Neovasc Reducer for Refractory Angina

(COSIRA-II Trial)

Recruiting at 57 trial locations

Overseen By COSIRA-II Study Team

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Shockwave Medical, Inc.

Must be taking: Anti-anginal agents

Disqualifiers: Recent ACS, Uncontrolled hypertension, Severe COPD, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests the Reducer system, a device to improve heart blood flow, in patients with severe chest pain not relieved by standard treatments and unsuitable for surgery. The device works by redirecting blood flow to needy heart areas by narrowing a vein. The Reducer system has been shown to improve chest pain symptoms and heart function in patients with persistent chest pain.

Will I have to stop taking my current medications?

The trial requires that you stay on your current stable regimen of anti-anginal medications for at least 12 months after randomization. You must have been on a stable dose for at least 60 days before joining the trial, and there should be no plans to change your medication during the trial.

What data supports the effectiveness of the Neovasc Reducer treatment for refractory angina?

The Neovasc Reducer treatment has shown effectiveness in improving symptoms for patients with refractory angina, as demonstrated in a randomized, double-blind, multi-center clinical trial involving 104 patients. Additionally, a meta-analysis incorporating data from several studies confirmed its efficacy and safety. ^{1 2 3 4 5}

How is the Neovasc Reducer System treatment different from other treatments for refractory angina?

The Neovasc Reducer System is unique because it is a device implanted in the heart's veins to improve blood flow and reduce chest pain, unlike traditional treatments that often involve medications or stents to open blocked arteries. ^{6 7 8 9 10}

Research Team

Timothy D Henry, MD

Principal Investigator

The Christ Hospital Health Network

Gregg W Stone, MD

Principal Investigator

Mt. Sinai Heart Health

Eligibility Criteria

This trial is for adults over 18 with persistent, severe angina (chest pain) despite using all recommended medications. They must have heart disease that can't be fixed with surgery or other procedures and show signs of reversible heart muscle stress due to poor blood flow in the left coronary artery. People with certain allergies, recent heart attacks, severe lung disease, or those who are pregnant or recently had COVID-19 cannot join.

Inclusion Criteria

I have tried at least three types of heart pain medication without changing them for 60 days.

I have had a test showing heart muscle stress due to narrowed arteries in the last year.

I am not a candidate for surgery or other procedures to improve blood flow to my heart as decided by heart specialists.

Exclusion Criteria

I cannot take certain blood thinners for 6 months.

I am in the hospital due to COVID-19.

My doctor expects me to live more than a year despite my other health issues.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the Reducer device implantation or are part of the sham-control group

6 months

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Annual visits for assessments and monitoring

Long-term follow-up

Extended monitoring of safety events and angina burden

5 years

Treatment Details

Interventions

• Implantation procedure with no device implanted (Procedure)
• Neovasc Reducer System (Coronary Sinus Reducer)

Trial Overview The study tests the Neovasc Reducer system's safety and effectiveness in reducing chest pain from angina when standard treatments don't work. One group gets the device implanted; another undergoes a sham procedure without implantation; a third non-randomized group is observed for additional safety data.

Participant Groups

Group I: Arm 3 (unblinded, non-randomized): Single Arm Registry Experimental Treatment 1 Intervention

Group II: Arm 1 (treatment arm):Implantation of the Reducer device Experimental Treatment 1 Intervention

Group III: Arm 2 (sham-control arm): Control (no device implantation) Placebo Group 1 Intervention

Neovasc Reducer System is already approved in Canada for the following indications:

Approved in Canada as Neovasc Reducer System for:

• Refractory angina pectoris with reversible myocardial ischemia

Who Is Running the Clinical Trial?

Shockwave Medical, Inc.

Lead Sponsor

Trials

38

Recruited

10,200+

Neovasc Inc.

Lead Sponsor

Trials

8

Recruited

1,400+

Findings from Research

The REDUCER-I study, involving 228 patients with refractory angina, showed a high procedural success rate of 99% and a very low incidence of major adverse cardiac events (MACE), indicating a strong safety profile for the coronary sinus Reducer.

Patients experienced significant improvements in angina severity, with 82% showing at least a one-class improvement in their angina classification after two years, and a notable reduction in those classified as CCS class III-IV from 70% to 15%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coronary sinus narrowing for the treatment of refractory angina: a multicentre prospective open-label clinical study (the REDUCER-I study). Verheye, S., Agostoni, P., Giannini, F., et al.[2023]

Refractory angina pectoris (RAP) remains a significant challenge in cardiovascular medicine, as many patients continue to experience severe symptoms despite optimal medical therapy and lack surgical options.

The review highlights the potential of the Reducer system, an innovative device that narrows the coronary sinus, as a new therapeutic option for patients with RAP, with ongoing clinical studies needed to determine its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coronary Sinus Reducer system™: A new therapeutic option in refractory angina patients unsuitable for revascularization. Ielasi, A., Todaro, MC., Grigis, G., et al.[2017]

The Coronary Sinus Reducer is a new device designed to treat chronic refractory angina by narrowing the coronary sinus, which may help improve blood flow to areas of the heart that are more ischemic.

In a recent clinical trial involving 104 patients, the device showed significant benefits in alleviating symptoms of refractory angina compared to a placebo, highlighting its potential as a new treatment option for patients not suitable for revascularization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The coronary sinus reducer: clinical evidence and technical aspects. Giannini, F., Aurelio, A., Jabbour, RJ., et al.[2018]

The Coronary Sinus Reducer was safely implanted in 15 patients with refractory angina, with no procedure-related adverse events reported during or after the procedure.

After 6 months, 12 out of 14 patients showed significant improvement in their angina scores, and measures of myocardial ischemia were also reduced, indicating the device's potential as an alternative treatment for patients not eligible for traditional revascularization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris: a prospective, open-label, multicenter, safety feasibility first-in-man study. Banai, S., Ben Muvhar, S., Parikh, KH., et al.[2010]

In a meta-analysis of 9 studies involving 846 patients, the implantation of the coronary sinus (CS) reducer significantly improved angina symptoms, with 76% of patients experiencing at least a 1-class improvement in their angina severity according to the Canadian Cardiovascular Society (CCS) angina score.

The procedure had a high success rate of 98% and a low complication rate, with no major complications reported, indicating that CS reducer implantation is a safe and effective option for patients with refractory angina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Coronary Sinus Reducer for Treatment of Refractory Angina: A Meta-analysis. Hochstadt, A., Itach, T., Merdler, I., et al.[2022]

The Edwards SAPIEN XT balloon-expandable valve allows for more frequent transfemoral access during transcatheter aortic valve implantation (TAVI), with successful access rates of 91.1% compared to 61.4% for the first-generation SAPIEN valve.

Short-term safety and performance outcomes for the SAPIEN XT are comparable to the original SAPIEN valve, with similar device success rates and 30-day safety endpoints, indicating that the new valve maintains efficacy while enabling use in patients with smaller arterial diameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective analysis of 30-day safety and performance of transfemoral transcatheter aortic valve implantation with Edwards SAPIEN XT versus SAPIEN prostheses. Eltchaninoff, H., Durand, E., Borz, B., et al.[2012]

The ACURATE neo aortic valve system is a self-expanding transcatheter device approved for treating severe aortic stenosis, showing wide clinical applicability since its CE mark in 2014.

Recent findings indicate that careful patient screening, size selection, and optimized positioning during implantation can significantly enhance the outcomes of using the ACURATE neo device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve implantation with the ACURATE neo valve: indications, procedural aspects and clinical outcomes. Kim, WK., Hengstenberg, C., Hilker, M., et al.[2020]

The ACURATE neo/TF self-expanding stent was successfully implanted in 14 out of 15 elderly patients (average age 83.3) with severe aortic stenosis, demonstrating a 0% mortality rate at 30 days and a low 6.7% mortality rate at 6 months.

The procedure significantly improved heart function, as shown by a dramatic decrease in mean transvalvular gradients from 44.2 mmHg to 7.7 mmHg, and half of the patients had no or trace paravalvular leak, indicating effective valve placement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Self-Expanding Transcatheter Aortic Valve Device for Transfemoral Implantation- Early Results of the First-in-Asia Implantation of the ACURATE Neo/TF(TM) System. Maeda, K., Kuratani, T., Torikai, K., et al.[2015]

Percutaneous coronary interventions (PCI) have become the most common treatment for coronary artery disease, but restenosis remains a significant challenge, particularly due to neointimal proliferation after stent implantation.

The use of drug-coated stents, which deliver antiproliferative agents like sirolimus and paclitaxel directly to the site, has shown promising results in reducing restenosis compared to conventional stents, indicating a potential shift in interventional cardiology practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-eluting stent: the emerging technique for the prevention of restenosis. Sheiban, I., Carrieri, L., Catuzzo, B., et al.[2015]

In a study involving 89 patients with an average age of 83.7 years, the ACURATE neo transcatheter heart valve demonstrated a high procedural success rate of 94.4% and low rates of major complications, with a 30-day major adverse cardiac and cerebrovascular event (MACCE) rate of 6.7%.

At one year, the valve showed effective performance with only 4.5% of patients experiencing moderate paravalvular regurgitation, and a significant improvement in heart function, as indicated by a reduction in patients classified as NYHA Class III/IV from 94.4% at baseline to 4.5% at one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transfemoral TAVI using the self-expanding ACURATE neo prosthesis: one-year outcomes of the multicentre "CE-approval cohort". Möllmann, H., Walther, T., Siqueira, D., et al.[2018]

References

1. France pubmed.ncbi.nlm.nih.gov

Coronary sinus narrowing for the treatment of refractory angina: a multicentre prospective open-label clinical study (the REDUCER-I study). [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Coronary Sinus Reducer system™: A new therapeutic option in refractory angina patients unsuitable for revascularization. [2017]

3. England pubmed.ncbi.nlm.nih.gov

The coronary sinus reducer: clinical evidence and technical aspects. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris: a prospective, open-label, multicenter, safety feasibility first-in-man study. [2010]

5. England pubmed.ncbi.nlm.nih.gov

Effectiveness of Coronary Sinus Reducer for Treatment of Refractory Angina: A Meta-analysis. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Prospective analysis of 30-day safety and performance of transfemoral transcatheter aortic valve implantation with Edwards SAPIEN XT versus SAPIEN prostheses. [2012]

7. France pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve implantation with the ACURATE neo valve: indications, procedural aspects and clinical outcomes. [2020]

8. Japan pubmed.ncbi.nlm.nih.gov

New Self-Expanding Transcatheter Aortic Valve Device for Transfemoral Implantation- Early Results of the First-in-Asia Implantation of the ACURATE Neo/TF(TM) System. [2015]

9. Italy pubmed.ncbi.nlm.nih.gov

Drug-eluting stent: the emerging technique for the prevention of restenosis. [2015]

10. France pubmed.ncbi.nlm.nih.gov

Transfemoral TAVI using the self-expanding ACURATE neo prosthesis: one-year outcomes of the multicentre "CE-approval cohort". [2018]