Cardio-Renal Syndrome, Chronic Heart Failure
Conditions
Brief summary
The renin-angiotensin-aldosterone axis has been found to be a key system involved in heart failure disease progression and it may be inhibited by renal sympathetic denervation. Therefore, a clear need exists for further strategies to beneficially manipulate the sympathetic activation that is characteristic of the heart failure disease process. The combined experience in the pilot studies and the EU randomized, controlled study indicates that the Paradise Catheter System can safely denervate renal sympathetic nerves of the kidney without significant periprocedural complications. Preliminary results of a pilot study of catheter-based renal denervation in a small number of CHF patients did not show evidence of safety issues but suggest improvements in CHF symptoms. This trial will explore the safety and feasibility of renal denervation in a significantly higher number of patients with chronic heart failure. Both inter-individual and intra-individual controls will be used in order to obtain sufficient data and to in order to enable both treatment and control group to receive renal denervation. Additionally, this feasibility trial to describe the safety and feasibility of renal denervation in patients with elevated sympathetic activity as in patients with chronic heart failure, will further the understanding of the role of renal nerves in the control of chronic heart failure and the pathogenesis of both ventricular remodeling and cardio-renal syndrome.
Interventions
PROCEDURERenal arteriography followed by renal denervation
Renal arteriography followed by renal denervation
PROCEDURESham Renal arteriography
Renal arteriography only
Sponsors
Interdisciplinary Center Clinical Trials (IZKS), University Medical Center Mainz
Universität des Saarlandes
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Unblinded interventionist, unblinded intervention team and blinded study team at each center, blinded patient.
Intervention model description
Prospective, randomized, double-blind, sham-controlled, multicenter, feasibility study. Patients will be screened for meeting eligibility and centrally randomized to receive either renal denervation or sham procedure. Best medical therapy will be provided to all patients. Optional cross-over after 12 months for sham-group patients. Thus, there is an intra-individual control in patients of the control group and all of the randomized patients are entitled to receive study treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patient with CHF diagnosed for at least 3 months prior to consent * 6-min walk distance ≤350 m * NYHA Class II-III symptoms of CHF * Systolic left ventricular dysfunction as assessed by echocardiogram with left ventricular ejection fraction \<45% * eGFR calculated (CKD-EPI) \>30 ml/min/1.73 m2 * NT-pro-BNP \>450 pg/ml, \>900 pg/ml for patients with atrial fibrillation * Optimal medical drug therapy according to current guidelines for CHF management. This medication may include loop diuretics, ACEi/ARBs, ARNI, SGLT-2 inhibitors, aldosterone antagonists, and beta-blockers, unless intolerance to any of the above is documented. Treatment for HF must be stable (including drug and dose) for 4 weeks prior to randomization, except diuretics (2 weeks stable) * Appropriate use of medical devices such as an implantable cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international guidelines, and if a device is required, it must have been implanted for at least 3 months prior to consent for CRT and 1 month prior to consent for ICD * Age ≥18 years and ≤80 years
Exclusion criteria
* Renal arterial anatomy that is ineligible for treatment * Myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 12 weeks prior to consent * Office systolic BP at screening \<90 mmHg * Clinically significant cardiac structural valvular disease, unless corrected by a properly functional prosthetic valve * Hypertrophic obstructive cardiomyopathy * Major surgery in the previous 12 weeks prior to consent * Hospitalization for decompensated CHF in the \<30 days prior to consent * Parenteral therapy for the treatment of CHF * Respiratory support (excluding sleep apnea therapy) * Left ventricular assist or planned heart transplantation * Patient is pregnant, nursing, or planning to be pregnant * Ineligibility to consent * Primary pulmonary hypertension (systolic PAP \>70 mmHg) * BMI ≥40 kg/m² * Any condition that would contraindicate the assessment of 6-min walk distance. * Patient has type I diabetes mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6 Minute Walk Test | 6 months | Change in 6-min walk distance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NT-proBNP | 6 months | Change in plasma NT-proBNP values |
| KCCQ | 6 months | Change in Overall Summary Score measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) |
| EQ-5D | 6 months | Change in Chronic Heart Failure Questionnaire Self-Administered Standardized format (CHQ-SAS) dyspnea score |
| eGFR | 6 months | chronic eGFR slope defined as eCRF |
Countries
Germany
Outcome results
None listed