PCI and Renal Denervation in Hypertensive Patients With Acute Coronary Syndromes (COMBI-RDN)

Combined Treatment With Percutaneous Coronary Intervention and Renal Denervation in Hypertensive Patients With Acute Coronary Syndromes.

Research hypothesis:

Is the treatment with renal denervation (RDN) early post ACS safe and effective and does it leads to improved cardiac function and attenuation of pathologic left ventricular remodelling? In a following study, the hypothesis will be tested in a larger ACS population with major adverse cardiovascular events (MACE) after ACS as the endpoint.

Rationale for conducting this study:

ACS i.e. ST-elevation myocardial infarction (STEMI) and non- ST-elevation myocardial infarction (non-STEMI) are the most important causes of morbidity and mortality in western societies. Hypertension is a major risk factor for development of ACS and heart failure but it also worsens the prognosis in patients after ACS. Our research highlights the combination therapy of PCI and RDN in an ACS patient population with simultaneous hypertension.

Primary objective:

The primary objective of this study is to establish safety and efficacy of combined treatment with PCI and renal denervation (RDN) in hypertensive patients with acute coronary syndromes (STEMI and non-STEMI ) having ventricular mass after 4 months as the primary variable.

Endpoints:

The primary end point is change in left ventricular mass (LVM) at 4 months evaluated by magnetic resonance imaging (MRI).

Secondary endpoints:, blood pressure (office and 24-h ABPM), and left ventricular volumes and ejection fraction.

Study Overview

• Status: Unknown
• Conditions: Hypertension; Acute Myocardial Infarction
• Intervention / Treatment: Procedure: Renal denervation

Detailed Description

The sympathetic nervous system plays a crucial role in the development and progression of hypertension and its adverse consequences. Despite the availability of numerous effective pharmacologic treatments, adequate blood pressure control is not achieved in a large number of subjects. Patients with essential hypertension generally have increased efferent sympathetic drive to the kidneys and an increased rate of sympathetic-nerve firing, possibly modulated by afferent signalling from renal sensory nerves. Recently developed endovascular catheter technology enables selective denervation of the human kidney. A safety and feasibility trial of this procedure identified substantial reductions of blood pressure without substantial procedure-related complications. The therapeutic value seems to be present not only in hypertension but may also be of interest in many clinical conditions e.g. heart failure, chronic end-stage renal disease and insulin resistance and diabetes.

The present study (COMBI-RDN) is a randomised clinical trial in 40 patients to investigate safety and efficacy of the combination of Percutan Coronar Interventiom (PCI) and renal denervation (RDN) where RDN is performed early after acute coronary syndrome (ACS). This study is considered a pilot study to evaluate efficacy and safety in patients with ACS. In a second phase there will be a randomised, multicenter study in approximately 2500 patients to demonstrate whether RDN early post ACS could decrease major adverse cardiovascular events in hypertensive patients with ACS.

Research hypothesis Is the treatment with renal denervation (RDN) early post ACS safe and effective and does it leads to improved cardiac function and attenuation of pathologic left ventricular remodelling?

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bert Andersson, Prof, MD; Phone Number: +46313427537; Email: bert.andersson@vgregion.se
• Study Contact Backup: Name: Elmir Omerovic, MD PhD; Phone Number: +46313427560; Email: elmir.omerovic@wlab.gu.se

Study Locations

• Sweden
  • Gothenburg, Sweden, 41345
    • Sahlgrenska University Hospital
    • Contact: Bert Andersson, Professor; Phone Number: +46 31 3427537; Email: bert.andersson@gu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female and/or male aged 18-80 years
3. Patients with ACS, i.e. STEMI, non-STEMI, treated with PCI
4. Medical history of treated (ongoing) hypertension, or hypertension discovered at the time of ACS, and office SBP >140 despite treatment with three antihypertensive drugs.
5. Ejection fraction >40%.

Exclusion Criteria:

1. Increased risk of pathological bleedings
2. Office systolic blood pressure <120
3. Renal artery abnormalities.
4. eGFR <30 mL/min
5. ICD or pacemaker, or any other metallic implant not compatible with MRI
6. Estimated survival time <1 year
7. Not oriented to person, place and time
8. Inability to understand given information about the study
9. Fertile female

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; One procedure will be performed using one of the CE-marked devices for renal denervation: Medtronic Symplicity Flex, Medtronic Symplicity Spyral or St Jude EnligHTN. Renal denervation is performed within seven days after PCI in patients with acute myocardial infarction and hypertension.	Procedure: Renal denervation; Medtronic Symplicity Flex, Medtronic Symplicity Spyral, or St Jude EnligHTN.
No Intervention: Control: Standard of care; Standard-of-care follow-up after ACS. Including nurse and physician out-patient visits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular remodelling	Change in left ventricular mass and volumes, as measured by magnetic resonance. Comparing intervention and control group.	At 4 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Office and 24-h ambulatory blood pressure	Change in blood pressure. Comparing intervention and control group.	At 4 months after renal denervation.

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden
• Investigators: Principal Investigator: Bert Andersson, Prof MD, Dept of Cardiology, Sahlgrenska University Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): March 1, 2016

Study Registration Dates

• First Submitted: September 11, 2014
• First Submitted That Met QC Criteria: October 22, 2014
• First Posted (Estimate): October 23, 2014

Study Record Updates

• Last Update Posted (Estimate): October 24, 2014
• Last Update Submitted That Met QC Criteria: October 23, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Acute Coronary Syndrome
• Other Study ID Numbers: 538-13