Neovasc Reducer for Refractory Angina

(COSIRA-II Trial)

Recruiting at 82 trial locations

Overseen By COSIRA-II Study Team

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Shockwave Medical, Inc.

Must be taking: Anti-anginal agents

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

380 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if the Neovasc Reducer System, a medical device, is safe and effective for individuals with hard-to-treat chest pain (refractory angina) who lack other options to improve heart blood flow. The study will assess the device's effectiveness across different groups, including those with specific heart conditions or mobility issues. Individuals experiencing chest pain for over 90 days, despite taking multiple medications and being unable to undergo other procedures, might be suitable candidates for this trial. As an unphased trial, it offers participants a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for refractory angina.

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 prior data suggests that the Neovasc Reducer System is safe for treating refractory angina?

Research has shown that the Neovasc Reducer System is generally safe for individuals with ongoing chest pain, known as refractory angina. This device narrows a large vein in the heart, and studies have found it is usually well-tolerated. Patients have reported feeling better and experiencing an improved quality of life, with only minor side effects.

In one study, the device provided significant relief from chest pain and enhanced the ability to perform daily activities. Another study confirmed these results, showing that long-term use of the device did not cause serious problems. Overall, the evidence supports the safety of the Neovasc Reducer System for those needing relief from persistent chest pain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The Neovasc Reducer System is unique because it offers a novel approach for managing refractory angina, a condition where patients continue to experience chest pain despite standard treatments like medications and lifestyle changes. Unlike conventional therapies that mainly focus on improving blood flow through medications, the Neovasc Reducer is a device that is implanted in the heart's coronary sinus to alter blood flow and reduce symptoms. Researchers are excited about this treatment because it provides an alternative for patients who have limited options, potentially improving quality of life without the need for more invasive procedures like bypass surgery.

What evidence suggests that the Neovasc Reducer System is effective for refractory angina?

Research has shown that the Neovasc Reducer System, which participants in this trial may receive, can help treat stubborn chest pain that doesn't improve with regular treatments. In earlier studies, 71% of patients experienced less chest pain after using the device, indicating many felt better. The procedure to implant the device succeeds about 98% of the time, so it usually goes smoothly. Patients reported feeling better overall and could walk longer distances after the treatment. Overall, the Neovasc Reducer appears to be a promising option for those with difficult-to-treat chest pain. Participants in this trial may also be assigned to a sham-control arm, where no device is implanted, to compare outcomes. ^{1 4 6 7 8}

Who Is on the Research Team?

Timothy D Henry, MD

Principal Investigator

The Christ Hospital Health Network

Gregg W Stone, MD

Principal Investigator

Mt. Sinai Heart Health

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Implantation procedure with no device implanted
• Neovasc Reducer System

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.

How Is the Trial Designed?

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 European Union, Canada for the following indications:

Approved in European Union as Neovasc Reducer System for:

• Refractory angina pectoris with reversible myocardial ischemia

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+

Published Research Related to This Trial

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]

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]

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]

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 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 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]

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 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 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]

Citations

1. jacc.org jacc.org/doi/10.1016/j.jcin.2025.06.012

Safety, Efficacy, and Effectiveness of Coronary Sinus ... The overall unweighted procedural success rate was 98.3% (95% CI: 97.0%-99.1%). Single-arm studies and RCT intervention arms demonstrated ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1402556

Efficacy of a Device to Narrow the Coronary Sinus in ... The device was also associated with improvement of at least one CCS angina class in 71% of the patients in the treatment group (37 of 52 ...

3. bmccardiovascdisord.biomedcentral.com bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-025-04617-8

The efficacy and safety of coronary sinus reducer in refractory ... CSR appears to be a safe and effective treatment for refractory angina, providing significant improvements in symptoms and quality of life.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34968714/

Effectiveness of Coronary Sinus Reducer for Treatment ... Procedure success was 98%, with no major and 3% nonmajor periprocedural complications. Post procedural SAQ scores and 6MWT distance were significantly improved.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05102019

NCT05102019 | Efficacy of the COronary SInus Reducer in ... To demonstrate the safety and effectiveness of the Shockwave Reducer for treatment of patients with refractory angina pectoris treated with maximally ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12275377/

The efficacy and safety of coronary sinus reducer in ... CSR appears to be a safe and effective treatment for refractory angina, providing significant improvements in symptoms and quality of life. The ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02710435

An Observational Study of the Neovasc Reducer™ System The purpose of this study is to collect long term data of the Reducer System in subjects with refractory angina pectoris.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7943892/

Long‐term outcomes of patients undergoing coronary ... Coronary sinus (CS) narrowing by reducer implantation has emerged as a safe and effective therapy for patients suffering from refractory angina.