Expand Management of Blood Pressure With Renal Denervation in Patients Undergoing Staged PCI for Advanced Coronary Artery diseasE (EMBRACE)

Expand Management of Blood Pressure With Renal Denervation in Patients Undergoing Staged PCI for Advanced Coronary Artery Disease

EMBRACE is a randomized, controlled, multicenter clinical study evaluating the effect of renal denervation on clinical adverse events in hypertensive patients undergoing staged percutaneous coronary intervention (PCI) for multivessel coronary artery disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Multivessel Coronary Artery Disease; Hypertension Resistant to Conventional Therapy
• Intervention / Treatment: Device: Renal denervation

Detailed Description

Hypertension remains one of the most important modifiable risk factors for cardiovascular morbidity and mortality worldwide. Despite the availability of multiple antihypertensive drug classes and evidence based treatment strategies, a substantial proportion of patients continue to have inadequately controlled blood pressure. Poor blood pressure control is particularly common among patients with multivessel coronary artery disease and is associated with increased adverse cardiovascular outcomes, including myocardial infarction, stroke, heart failure, progression of renal dysfunction, and increased mortality.

Renal sympathetic nerve activity plays a central role in the pathophysiology of hypertension through modulation of renal blood flow, sodium and water retention, renin release, and systemic sympathetic tone. Renal denervation is a catheter based procedure designed to disrupt renal sympathetic afferent and efferent nerves by delivering energy to the renal artery wall. Multiple randomized clinical studies have demonstrated that renal denervation can reduce blood pressure in patients with uncontrolled hypertension, with sustained effects during follow up and an acceptable safety profile when performed using contemporary devices and techniques.

Patients with multivessel coronary artery disease undergoing percutaneous coronary intervention represent a particularly relevant population in which blood pressure control is of critical importance. In many cases, coronary revascularization is performed as a staged procedure, with an initial index PCI followed by a planned staged PCI to complete revascularization of remaining significant coronary lesions. This staged approach allows for optimization of patient safety and procedural efficiency, particularly in patients with complex coronary anatomy or a high ischemic burden.

The EMBRACE study is designed to evaluate the benefit of renal denervation in improving clinical outcomes in patients with multivessel coronary artery disease undergoing staged percutaneous coronary intervention. This study is a prospective, randomized, controlled, multicenter clinical investigation. Eligible patients are adults with multivessel coronary artery disease undergoing staged PCI who have hypertension defined as persistent elevation of office systolic blood pressure despite treatment with two or more antihypertensive medications. Following confirmation of eligibility and completion of the index PCI, patients who remain eligible prior to the planned staged PCI are randomized in a 1:1 allocation ratio to receive renal denervation in addition to standard care or standard care alone.

Renal denervation is performed using a commercially available catheter based renal denervation system in accordance with the manufacturer's instructions for use. The procedure is carried out via standard endovascular access and is performed either during the staged PCI procedure or as a standalone catheter based intervention, depending on procedural planning and investigator judgment. All patients continue to receive guideline directed medical therapy for hypertension and coronary artery disease throughout the study.

Patients randomized to the control group undergo staged PCI and continue standard medical therapy without renal denervation. Antihypertensive medications are managed according to routine clinical practice, with adjustments permitted at the discretion of the treating physician to ensure patient safety and appropriate blood pressure control.

The primary objective of the EMBRACE study is to assess the effect of renal denervation on clinically meaningful cardiovascular outcomes in this high-risk population. The primary endpoint is a hierarchical composite endpoint analyzed using a win-ratio methodology, comparing patients randomized to renal denervation versus standard care. This hierarchical clinical outcome framework allows prioritization of more severe and clinically relevant events over less severe outcomes, providing an integrated assessment of net clinical benefit. The hierarchical outcome includes major adverse cardiovascular and cerebrovascular events such as death and other serious cardiovascular outcomes, followed by additional clinically relevant events as defined in the study protocol.

Secondary objectives of the EMBRACE study include evaluation of blood pressure control, changes in antihypertensive medication burden, renal safety, and procedure-related safety outcomes. Blood pressure measurements are obtained using standardized office blood pressure assessment methods at baseline and predefined follow-up intervals. Changes in blood pressure and medication use are evaluated as secondary and supportive endpoints, providing mechanistic context for observed clinical effects.

Safety endpoints include assessment of renal artery-related complications, access-site complications, renal function changes, and other adverse events related to renal denervation and percutaneous coronary intervention. Clinical events are collected throughout the follow-up period to allow comprehensive evaluation of both efficacy and safety.

The EMBRACE study is conducted in accordance with the principles of the Declaration of Helsinki, Good Clinical Practice guidelines, and applicable regulatory requirements. Written informed consent is obtained from all participants prior to performance of any study specific procedures. Study oversight is provided through standardized monitoring and safety reporting mechanisms to ensure data integrity and participant safety.

By integrating renal denervation into the staged PCI care pathway, EMBRACE seeks to address an important unmet clinical need in patients with advanced coronary artery disease and uncontrolled hypertension. The study aims to provide clinical evidence regarding the safety and effectiveness of renal denervation in this population and to clarify the potential role of this intervention as an adjunct to contemporary revascularization and pharmacologic treatment strategies.

The results of EMBRACE may inform future treatment approaches for patients with multivessel coronary artery disease and persistent hypertension, a population at particularly high risk for adverse cardiovascular outcomes. If renal denervation demonstrates meaningful and durable blood pressure reduction without compromising procedural safety, it may represent an important therapeutic option to optimize cardiovascular risk reduction in these patients.

List of abbreviation:

PCI - Percutaneous Coronary Intervention SoC - Standard of Care MACCE - Major Adverse Cardiovascular and Cerebrovascular Events MACE - Major Adverse Cardiovascular Events

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Estelle Darrau, Ph.D; Phone Number: +33 0675657408; Email: edarrau@cerc-europe.org
• Study Contact Backup: Name: laure Morsiani, Ph.D; Phone Number: +33 0176739236; Email: lmorsiani@cerc-europe.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject with multi-vessel disease
• Having successful index PCI and planned staged procedure within 1-6 weeks to complete revascularization
• Subjects ≥21 years of age
• Office systolic blood pressure at index procedure and/or staged procedure (systolic blood pressure >140 mmHg) while taking 2 or more antihypertensive drugs
• Subject agrees to have all study procedures performed, and is competent and willing to provide written, informed consent to participate in this clinical study prior to staged procedure

Exclusion Criteria:

• - Contraindication for RDN outlined by IFU
• Acute MI at time of the staged PCI procedure (AMI at time of the index PCI is allowed)
• Subject has undergone prior renal denervation.
• Subject has renal artery anatomy that is ineligible for RDN treatment per Symplicity Spyral™ IFU
• Known secondary cause (e.g., renal artery stenosis, primary aldosteronism, pheochromocytoma, Cushing's syndrome, or other identifiable etiologies).
• Severe renal failure (eGFR <30 ml/min/1.73 m²)
• Known LVEF <30%
• Known history of polycystic kidney disease, unilateral kidney, or undergone renal transplant
• Mechanical circulatory support during PCI
• Subject is under judicial protection, tutorship or curatorship
• Failure of index procedure
• Acute MI, severe renal failure, need for mechanical circulatory support, or legal incapacity between the index and staged procedures resulting in loss of eligibility.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Renal denervation; Renal denervation (patient continue hypertension medication if applicable)	Device: Renal denervation; Catheter-based renal denervation performed during a standard renal artery catheterization procedure using a dedicated renal denervation system, according to the study protocol. The procedure is performed in addition to ongoing antihypertensive medical therapy, which is continued throughout the study as clinically indicated.
No Intervention: Control; Standard of care (patient continue hypertension medication if applicable)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary endpoint: Win Ratio of Hierarchical Composite Endpoint After Staged PCI	The primary endpoint will be assessed using a win ratio, a statistical method that compares treatment groups based on a hierarchical evaluation of clinically ordered outcomes. Patients will be compared pairwise between treatment groups, and outcomes will be evaluated in the following predefined order of clinical importance after staged PCI: Cardiovascular death Stroke Myocardial infarction Number of hospitalizations for heart failure Hospitalization for hypertensive crisis (yes/no) Number of hypertensive emergencies Change in office systolic blood pressure Change in antihypertensive medication (increase, no change, or decrease in number and/or dosage) For each patient pair, the first outcome in the hierarchy that differs between patients will determine the winner. The win ratio will be calculated as the total number of wins in the investigational treatment group divided by the total number of wins in the control group.	2 Years post procedure
Primary safety endpoint : Major vascular access site complications	Number of participants who experience Major vascular access site complications within 30 d after the staged PCI.	30 days after staged PCI
Primary safety endpoint: Contrast-associated acute kidney injury (CA-AKI) (≥25% increase in serum creatinine within 48-72 hours)	Number of patient having ≥25% increase in serum creatinine within 48-72 hours after the procedure	30 days after staged PCI
Primary safety endpoint: Renal artery complications	Number of patients with renal artery complications (dissection requiring intervention) and renal artery stenosis (requiring intervention)	30 days after staged PCI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary endpoint	- ambulatory blood pressure change (increase - no change or decrease) between groups	2, 3 & 5 Years after procedure
Secondary endpoints: Quality of life	improvement of QoL (EQ-5D-5L)	2, 3 & 5 years after staged PCI
Secondary endpoints: Health economics	Incremental Cost-Effectiveness Ratio (enal denervation plus standard of care versus standard of care alone)	2, 3 & 5 years after staged PCI
Secondary endpoint: Time to first hypertension emergency	A hypertensive crisis is defined by 2018 ESC/ESH Guidelines as a unplanned hospitalization due to severe elevation in blood pressure, typically ≥ 180 mmHg systolic and/or ≥ 120 mmHg diastolic, encompassing both hypertensive emergencies and hypertensive urgencies.	2, 3 & 5 Years
Secondary endpoint: kidney function	eGFR measurement	2, 3, 5 Years

Collaborators and Investigators

• Sponsor: Ceric Sàrl
• Investigators: Principal Investigator: Felix Mahfoud, Prof., Departement Biomedizin DBM Hebelstrasse; Principal Investigator: Roxana Mehran, Prof., Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2030
• Study Completion (Estimated): November 1, 2033

Study Registration Dates

• First Submitted: May 4, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypertension Resistant to Conventional Therapy
• Other Study ID Numbers: EMBRACE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No