DENEX Renal Denervation in Patients With Hypertension on no Antihypertensive Medications
Primary Purpose
Hypertension, Vascular Diseases, Cardiovascular Diseases
Status
Recruiting
Phase
Not Applicable
Locations
Greece
Study Type
Interventional
Intervention
Renal denervation
Renal angiography
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension focused on measuring Renal Denervation
Eligibility Criteria
Inclusion Criteria:
- Subject aged 18 to 80 years old at the time of signing the informed consent
- Subject who is drug-naïve or willing to discontinue current antihypertensive treatment (not on antihypertensive medications for at least 4 weeks prior to Screening Visit 1) at Screening Visit 1 through the 3-month post-procedure visit. Drug-naïve is defined as those with no previous exposure to antihypertensive medications.
Subject who meets all of the following blood pressure measurements:
- Office Systolic Blood Pressrue (SBP) < 180 mmHg at Screening Visit 1
- Office SBP ≥ 150 mmHg and < 180 mmHg, and office diastolic blood pressure (DBP) ≥ 90 mmHg at Screening Visit 2
- 24-h ambulatory SBP ≥ 140 mmHg and < 170 mmHg at Screening Visit 2
- Subject who voluntarily decides to participate in this clinical study and sign the written consent.
- Subject who willing and able to complete all clinical investigation-related procedures and assessments
Exclusion Criteria:
Subject with renal anatomy that is ineligible for treatment:
- Diameter of main renal artery for each kidney is < 3 mm or > 8 mm OR presence of accessory renal arteries (ARAs) with a diameter < 3 mm
- Presence of fibromuscular dysplasia
- Presence of kidney tumors or secretory tumors in the adrenal gland
- > 50% stenosis in any treatable vessel
- Presence of aneurysm (any localized increase in vessel diameter)
- Treatment area within 5 mm segment in the renal artery contains an atheroma, calcification, or a renal artery stent
- A single functioning kidney
- Polycystic kidney disease
- Subject with prior renal denervation, renal artery stenting, renal artery angioplasty, renal nephrectomy, or renal transplant
- Subject with type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (HbA1c over 10.0%)
- Subject with epidermal growth factor receptor (eGFR) < 45 mL/min/1.73 m2, using the 4-variable modification of diet in renal disease (MDRD) clinical investigation calculation
- Subject taking sodium glucose co-transporter 2 (SGLT2) inhibitors or glucagon like peptide-1 (GLP-1) agonists that have been prescribed < 90 days prior to Screening Visit 1 or necessary to remain on these medications for duration of clinical investigation
- Subject with ≥ 1 episode of orthostatic hypotension not related to medication changes within the past year prior to Screening Visit 1
- Documented repeated (> 1) hospitalization for hypertensive crisis within the 12 months and/or any hospitalization for hypertensive crisis within the 3months prior to Screening Visit 1.
- Subject requiring chronic oxygen support or mechanical ventilation (other than nocturnal respiratory support for sleep apnea)
- Subject with primary pulmonary hypertension
- Subject with untreated secondary cause of hypertension (known or suspected) or taking medications that increase sympathetic tone that could contribute to hypertension
- Subject with frequent or chronic pain that requires treatment with NSAIDs for two or more days per week during the last month prior to Screening Visit 2 (aspirin and clopidogrel permitted for cardiovascular risk reduction)
- Human immunodeficiency virus (HIV) on anti-retroviral drug therapy but without documentation that hypertension preceded initiation of anti-retroviral drug therapy
- Subject with a history of myocardial infarction, stable or unstable angina, transient ischemic attack, cerebrovascular accident, heart failure, or atrial fibrillation within 3 months prior to Screening Visit 1
- Subject who requires more than occasional use (e.g., PRN) of narcotic drugs over the month prior to Screening Visit 1
- Subject currently taking anti-mineralocorticoid medications, unless weaned off by ≥ 8 weeks prior to Screening Visit 1
- Subject with a history of bleeding diathesis or coagulopathy or subject who refuses blood transfusions
- Subject working night shifts
- Subject with a medical history of contraindications, anaphylactic reactions, or uncontrollable allergic reactions to contrast agents
- Subject using active implantable medical devices (Implantable Cardioverter Defibrillator [ICD] or Cardiac Resynchronization Therapy Device [CRT-D], neuromodulation device, spinal cord stimulator, pressure reflector, etc.)
- Subject with scheduled or planned surgery that may affect clinical investigation endpoints, in the opinion of the investigator
- Subject has a documented condition that would prohibit or interfere with ability to obtain an accurate blood pressure measurement using the protocol-specified automatic/office blood pressure monitor (e.g., upper arm circumference outside cuff size ranges available by geography or arrhythmia that interferes with automatic monitor's pulse sensing and prohibits an accurate measurement).
- Subject with documented confounding medical condition that may adversely affect the safety of the subject, in the opinion of the investigator (e.g. clinically significant peripheral vascular disease, aortic aneurysm, severe cardiac valve stenosis for which a significant reduction of blood pressure is contraindicated, or bleeding disorders such as thrombocytopenia, hemophilia, or significant anemia,)
- Subject with known unresolved history of drug use or alcohol dependency, lacks ability to comprehend or follow instructions, or would be unlikely or unable to comply with clinical investigation follow-up requirements
- Subject currently enrolled in a concurrent investigational drug or device clinical investigation, unless approved by clinical investigation sponsor
- 23)25) Pregnant, nursing, or planning to become pregnant during the course of the clinical investigation or follow-up. A negative pregnancy test is required for all women of child- bearing potential.
- Subject who is unsuitable for the study for any reason as judged by the investigator
Sites / Locations
- University of Athens Hippocratio HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
DENEX Renal denervation
Sham control
Arm Description
Subjects are treated with the renal denervation procedure after randomization
Subjects are treated with renal angiography
Outcomes
Primary Outcome Measures
Change in 24-h ambulatory systolic blood pressure
Change in 24-h ambulatory systolic blood pressure from baseline to 3 months post-procedure
Incidence of MAE within 3 months post-procedure
Incidence of MAE within 3 months post-procedure
Secondary Outcome Measures
Changes in 24-h ambulatory systolic blood pressure
Changes in 24-h ambulatory SBP from baseline to 6, 12, and 24 months post-procedure
Changes in 24-h ambulatory diastolic blood pressure
Changes in 24-h ambulatory DBP from baseline to 3, 6, 12, and 24 months post-procedure
Changes in office systolic blood pressure
Changes in office SBP from baseline to 1, 3, 6, 12, and 24 months post-procedure
Changes in office diastolic blood pressure
Changes in office DBP from baseline to 1, 3, 6, 12, and 24 months post-procedure
Incidence of achieving target office systolic blood pressure (< 140 mmHg)
Incidence of achieving target office SBP (< 140 mmHg) from baseline to 1, 3, 6, 12, and 24 months post-procedure
Changes in heart rate
Changes in heart rate from baseline to 3, 6, 12, and 24 months post-procedure
Incidence of AEs, SAEs, ADE, and SADE
Incidence of Adverse Events (AEs), SAEs, Adverse Device Effects (ADE), and Serious Adverse Device Effects (SADE) at 1, 3, 6, 12, and 24 months post-procedure
Incidence of MAE
Incidence of MAEs at 6, 12, and 24 months post-procedure
Incidence of significant embolic event resulting in end-organ damage, incidence of renal artery perforation requiring intervention, incidence of renal artery dissection requiring intervention, incidence of vascular complications
Incidence of significant embolic event resulting in end-organ damage, incidence of renal artery perforation requiring intervention, incidence of renal artery dissection requiring intervention, incidence of vascular complications at 1 month post-procedure
Incidence of all-cause mortality
Incidence of all-cause mortality at 3, 6, 12, and 24 months post-procedure
Incidence of end-stage renal disease, incidence of ≥ 40% decline in eGFR, incidence of new myocardial infarction, incidence of new stroke, incidence of renal artery reintervention
Incidence of end-stage renal disease, incidence of ≥ 40% decline in estimated glomerular filtration rate (eGFR), incidence of new myocardial infarction, incidence of new stroke, incidence of renal artery reintervention at 1, 3, 6, 12, and 24 months post-procedure
Incidence of major bleeding according to Thrombolysis in Myocardial Infarction (TIMI) definition
Incidence of major bleeding according to Thrombolysis in Myocardial Infarction (TIMI) definition at 1, 3, 6, 12, and 24 months post-procedure (intracranial hemorrhage, ≥ 5 g/dL decrease in hemoglobin concentration, ≥ 15% absolute decrease in hematocrit, or death due to bleeding within 7 days of procedure)
Incidence or increase in serum creatinine > 50%
Incidence or increase in serum creatinine > 50% at 1, 3, 6, 12, and 24 months post-procedure
Incidence of new renal artery stenosis > 70%
Incidence of new renal artery stenosis > 70% at 3 months post-procedure, as assessed by Computed Tomography (CT), Magnetic Resonance Angiography (MRA), or Doppler Ultrasonography (DUS)
Incidence of hospitalization for hypertensive crisis not related to confirmed non-adherence or the CIP
Incidence of hospitalization for hypertensive crisis not related to confirmed non-adherence or the CIP at 1, 3, 6, 12, and 24 months post-procedure
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04535050
Brief Title
DENEX Renal Denervation in Patients With Hypertension on no Antihypertensive Medications
Official Title
A Prospective, Multicenter, Sham-controlled, Single-blinded, Randomized, Pilot Study to Evaluate the Safety and Effectiveness of DENEX Renal Denervation System in Patients With Uncontrolled Hypertension Not Treated With Anti-HTN Medication
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 20, 2022 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
April 15, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kalos Medical
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The objective of this study is to evaluate the safety and effectiveness of renal denervation using DENEX System in patients with hypertension without antihypertensive medication, compared with the sham group.
Detailed Description
DENEX system developed by Kalos Medical Inc. is a renal denervation system to efficiently block the sympathetic nerve of the kidney with minimal invasive procedure. It was developed to block the sympathetic nerves distributed in blood vessel wall by delivering high frequency energy to the renal artery for the purpose of treating hypertension.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Vascular Diseases, Cardiovascular Diseases
Keywords
Renal Denervation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
DENEX Renal denervation
Arm Type
Experimental
Arm Description
Subjects are treated with the renal denervation procedure after randomization
Arm Title
Sham control
Arm Type
Sham Comparator
Arm Description
Subjects are treated with renal angiography
Intervention Type
Device
Intervention Name(s)
Renal denervation
Intervention Description
Renal Denervation: DENEX system
Intervention Type
Procedure
Intervention Name(s)
Renal angiography
Intervention Description
Renal angiography
Primary Outcome Measure Information:
Title
Change in 24-h ambulatory systolic blood pressure
Description
Change in 24-h ambulatory systolic blood pressure from baseline to 3 months post-procedure
Time Frame
from baseline to 3 months post-procedure
Title
Incidence of MAE within 3 months post-procedure
Description
Incidence of MAE within 3 months post-procedure
Time Frame
within 3 months post-procedure
Secondary Outcome Measure Information:
Title
Changes in 24-h ambulatory systolic blood pressure
Description
Changes in 24-h ambulatory SBP from baseline to 6, 12, and 24 months post-procedure
Time Frame
from baseline to 6, 12, and 24 months post-procedure
Title
Changes in 24-h ambulatory diastolic blood pressure
Description
Changes in 24-h ambulatory DBP from baseline to 3, 6, 12, and 24 months post-procedure
Time Frame
from baseline to 3, 6, 12, and 24 months post-procedure
Title
Changes in office systolic blood pressure
Description
Changes in office SBP from baseline to 1, 3, 6, 12, and 24 months post-procedure
Time Frame
from baseline to 1, 3, 6, 12, and 24 months post-procedure
Title
Changes in office diastolic blood pressure
Description
Changes in office DBP from baseline to 1, 3, 6, 12, and 24 months post-procedure
Time Frame
from baseline to 1, 3, 6, 12, and 24 months post-procedure
Title
Incidence of achieving target office systolic blood pressure (< 140 mmHg)
Description
Incidence of achieving target office SBP (< 140 mmHg) from baseline to 1, 3, 6, 12, and 24 months post-procedure
Time Frame
from baseline to 1, 3, 6, 12, and 24 months post-procedure
Title
Changes in heart rate
Description
Changes in heart rate from baseline to 3, 6, 12, and 24 months post-procedure
Time Frame
from baseline to 3, 6, 12, and 24 months post-procedure
Title
Incidence of AEs, SAEs, ADE, and SADE
Description
Incidence of Adverse Events (AEs), SAEs, Adverse Device Effects (ADE), and Serious Adverse Device Effects (SADE) at 1, 3, 6, 12, and 24 months post-procedure
Time Frame
at 1, 3, 6, 12, and 24 months post-procedure
Title
Incidence of MAE
Description
Incidence of MAEs at 6, 12, and 24 months post-procedure
Time Frame
at 6, 12, and 24 months post-procedure
Title
Incidence of significant embolic event resulting in end-organ damage, incidence of renal artery perforation requiring intervention, incidence of renal artery dissection requiring intervention, incidence of vascular complications
Description
Incidence of significant embolic event resulting in end-organ damage, incidence of renal artery perforation requiring intervention, incidence of renal artery dissection requiring intervention, incidence of vascular complications at 1 month post-procedure
Time Frame
at 1 month post-procedure
Title
Incidence of all-cause mortality
Description
Incidence of all-cause mortality at 3, 6, 12, and 24 months post-procedure
Time Frame
at 3, 6, 12, and 24 months post-procedure
Title
Incidence of end-stage renal disease, incidence of ≥ 40% decline in eGFR, incidence of new myocardial infarction, incidence of new stroke, incidence of renal artery reintervention
Description
Incidence of end-stage renal disease, incidence of ≥ 40% decline in estimated glomerular filtration rate (eGFR), incidence of new myocardial infarction, incidence of new stroke, incidence of renal artery reintervention at 1, 3, 6, 12, and 24 months post-procedure
Time Frame
at 1, 3, 6, 12, and 24 months post-procedure
Title
Incidence of major bleeding according to Thrombolysis in Myocardial Infarction (TIMI) definition
Description
Incidence of major bleeding according to Thrombolysis in Myocardial Infarction (TIMI) definition at 1, 3, 6, 12, and 24 months post-procedure (intracranial hemorrhage, ≥ 5 g/dL decrease in hemoglobin concentration, ≥ 15% absolute decrease in hematocrit, or death due to bleeding within 7 days of procedure)
Time Frame
at 1, 3, 6, 12, and 24 months post-procedure
Title
Incidence or increase in serum creatinine > 50%
Description
Incidence or increase in serum creatinine > 50% at 1, 3, 6, 12, and 24 months post-procedure
Time Frame
at 1, 3, 6, 12, and 24 months post-procedure
Title
Incidence of new renal artery stenosis > 70%
Description
Incidence of new renal artery stenosis > 70% at 3 months post-procedure, as assessed by Computed Tomography (CT), Magnetic Resonance Angiography (MRA), or Doppler Ultrasonography (DUS)
Time Frame
at 3 months post-procedure
Title
Incidence of hospitalization for hypertensive crisis not related to confirmed non-adherence or the CIP
Description
Incidence of hospitalization for hypertensive crisis not related to confirmed non-adherence or the CIP at 1, 3, 6, 12, and 24 months post-procedure
Time Frame
at 1, 3, 6, 12, and 24 months post-procedure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject aged 18 to 80 years old at the time of signing the informed consent
Subject who is drug-naïve or willing to discontinue current antihypertensive treatment (not on antihypertensive medications for at least 4 weeks prior to Screening Visit 1) at Screening Visit 1 through the 3-month post-procedure visit. Drug-naïve is defined as those with no previous exposure to antihypertensive medications.
Subject who meets all of the following blood pressure measurements:
Office Systolic Blood Pressrue (SBP) < 180 mmHg at Screening Visit 1
Office SBP ≥ 150 mmHg and < 180 mmHg, and office diastolic blood pressure (DBP) ≥ 90 mmHg at Screening Visit 2
24-h ambulatory SBP ≥ 140 mmHg and < 170 mmHg at Screening Visit 2
Subject who voluntarily decides to participate in this clinical study and sign the written consent.
Subject who willing and able to complete all clinical investigation-related procedures and assessments
Exclusion Criteria:
Subject with renal anatomy that is ineligible for treatment:
Diameter of main renal artery for each kidney is < 3 mm or > 8 mm OR presence of accessory renal arteries (ARAs) with a diameter < 3 mm
Presence of fibromuscular dysplasia
Presence of kidney tumors or secretory tumors in the adrenal gland
> 50% stenosis in any treatable vessel
Presence of aneurysm (any localized increase in vessel diameter)
Treatment area within 5 mm segment in the renal artery contains an atheroma, calcification, or a renal artery stent
A single functioning kidney
Polycystic kidney disease
Subject with prior renal denervation, renal artery stenting, renal artery angioplasty, renal nephrectomy, or renal transplant
Subject with type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (HbA1c over 10.0%)
Subject with epidermal growth factor receptor (eGFR) < 45 mL/min/1.73 m2, using the 4-variable modification of diet in renal disease (MDRD) clinical investigation calculation
Subject taking sodium glucose co-transporter 2 (SGLT2) inhibitors or glucagon like peptide-1 (GLP-1) agonists that have been prescribed < 90 days prior to Screening Visit 1 or necessary to remain on these medications for duration of clinical investigation
Subject with ≥ 1 episode of orthostatic hypotension not related to medication changes within the past year prior to Screening Visit 1
Documented repeated (> 1) hospitalization for hypertensive crisis within the 12 months and/or any hospitalization for hypertensive crisis within the 3months prior to Screening Visit 1.
Subject requiring chronic oxygen support or mechanical ventilation (other than nocturnal respiratory support for sleep apnea)
Subject with primary pulmonary hypertension
Subject with untreated secondary cause of hypertension (known or suspected) or taking medications that increase sympathetic tone that could contribute to hypertension
Subject with frequent or chronic pain that requires treatment with NSAIDs for two or more days per week during the last month prior to Screening Visit 2 (aspirin and clopidogrel permitted for cardiovascular risk reduction)
Human immunodeficiency virus (HIV) on anti-retroviral drug therapy but without documentation that hypertension preceded initiation of anti-retroviral drug therapy
Subject with a history of myocardial infarction, stable or unstable angina, transient ischemic attack, cerebrovascular accident, heart failure, or atrial fibrillation within 3 months prior to Screening Visit 1
Subject who requires more than occasional use (e.g., PRN) of narcotic drugs over the month prior to Screening Visit 1
Subject currently taking anti-mineralocorticoid medications, unless weaned off by ≥ 8 weeks prior to Screening Visit 1
Subject with a history of bleeding diathesis or coagulopathy or subject who refuses blood transfusions
Subject working night shifts
Subject with a medical history of contraindications, anaphylactic reactions, or uncontrollable allergic reactions to contrast agents
Subject using active implantable medical devices (Implantable Cardioverter Defibrillator [ICD] or Cardiac Resynchronization Therapy Device [CRT-D], neuromodulation device, spinal cord stimulator, pressure reflector, etc.)
Subject with scheduled or planned surgery that may affect clinical investigation endpoints, in the opinion of the investigator
Subject has a documented condition that would prohibit or interfere with ability to obtain an accurate blood pressure measurement using the protocol-specified automatic/office blood pressure monitor (e.g., upper arm circumference outside cuff size ranges available by geography or arrhythmia that interferes with automatic monitor's pulse sensing and prohibits an accurate measurement).
Subject with documented confounding medical condition that may adversely affect the safety of the subject, in the opinion of the investigator (e.g. clinically significant peripheral vascular disease, aortic aneurysm, severe cardiac valve stenosis for which a significant reduction of blood pressure is contraindicated, or bleeding disorders such as thrombocytopenia, hemophilia, or significant anemia,)
Subject with known unresolved history of drug use or alcohol dependency, lacks ability to comprehend or follow instructions, or would be unlikely or unable to comply with clinical investigation follow-up requirements
Subject currently enrolled in a concurrent investigational drug or device clinical investigation, unless approved by clinical investigation sponsor
23)25) Pregnant, nursing, or planning to become pregnant during the course of the clinical investigation or follow-up. A negative pregnancy test is required for all women of child- bearing potential.
Subject who is unsuitable for the study for any reason as judged by the investigator
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
EunHa Choi
Phone
82-2-527-5417
Email
eunha.choi@kalosmedical.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Konstantinos Tsioufis, Professor
Organizational Affiliation
National and Kapodistrian University of Athens, Greece
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Felix Mahfoud, Professor
Organizational Affiliation
Saarland University Hospital, Homburg
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Massimo Volpe, Professor
Organizational Affiliation
University of Roma La Sapienza
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Jacek Kadziela, Professor
Organizational Affiliation
Narodowy Instytut Kardiologii Stefana kardynała Wyszyńskiego, Poland
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Athens Hippocratio Hospital
City
Athens
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tsioufis Costas
First Name & Middle Initial & Last Name & Degree
Tsioufis Costas
12. IPD Sharing Statement
Plan to Share IPD
No
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DENEX Renal Denervation in Patients With Hypertension on no Antihypertensive Medications
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