Hypertension
Conditions
Brief summary
The primary objective of the THRIVE Pivotal study is to demonstrate the adjunctive effectiveness and the safety of the TIVUS system in: 1. subjects with uncontrolled hypertension (HTN) receiving 0 - 2 anti-hypertensive drugs of different classes in whom the anti-hypertensive medications will be stopped for a 4-week wash-out period before RDN/Sham procedure and during 2 months after procedure. 2. subjects with controlled hypertension receiving 1 - 2 anti-hypertensive drugs of different classes and who accept to be off-medications for a 4-week wash-out period before RDN/Sham procedure and 2 months after the procedure
Detailed description
THRIVE is an international, multicenter, randomized, double blind, sham-controlled study, designed to demonstrate the adjunctive effectiveness and safety of the TIVUS System in hypertensive subjects while subjects are maintained off-antihypertensive medications for a 4-week wash-out period before RDN/Sham procedure and 2 months after procedure. At two months after procedure, subjects with uncontrolled hypertension are put back on antihypertensive medication according to a medication escalation protocol. Unblinding will be performed at 6 months. Uncontrolled sham subjects can cross-over to RDN procedure at 6-months. The sham procedure will be minimally invasive to reduce risk to subjects. All subjects treated with TIVUS will be followed for a maximum of 36 months post procedure.
Interventions
DEVICETIVUS™ Renal Denervation System
Renal artery catheterization procedure used to denervate the renal sympathetic nerves in the perivascular space using ultrasound energy.
OTHERSham
For those subjects randomized to the sham control, the angiogram will serve as the sham procedure.
Sponsors
SoniVie Inc.
NAMSA
European Cardiovascular Research Center
IQVIA Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The subjects and all study personnel taking follow-up blood pressure measurements will be blinded to the randomization up to 6 months post-randomization. Subjects will complete a blinding assessment prior to hospital discharge, at 2M and 6M FU. Study unblinding will occur at 6-months FU. ABPM measurements will be sent to an independent core lab for data cleaning and analysis and will be blinded to the randomization assignment.
Intervention model description
2:1 randomization will be used to assign subjects to treatment (RDN) or control (sham). Randomization will occur immediately after the renal angiogram.
Eligibility
Sex/Gender
ALL
Age
22 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Appropriately signed and dated informed consent 2. Male and female adults with age between ≥22 and ≤75 years at time of consent 3. Documented history of hypertension 4. Previously or currently prescribed antihypertensive therapy 5. Subject has an office BP (average of 3 seated measurements) of: 1. Uncontrolled BP: ≥ 140/90 mmHg \<180/110 mmHg at Screening Visit (V0) while stable for at least 4 weeks on 0-2 anti-hypertensive medications of different classes\* and willing to stop anti-hypertensive medication(s) for 4 weeks wash-out and 2-months post-procedure, (subjects with a history of treatment with anti-hypertensive medications but are not currently taking any at screening will undergo a 4-week run-in period) or, 2. Controlled BP: \< 140/90 mmHg while stable for at least 4 weeks on 1-2 antihypertensive medications of different classes and willing to stop anti-hypertensive medication(s) for 4 weeks wash-out and 2-months post-procedure 6. Able and willing to comply with all study procedures 7. Subject is willing to have and is a good candidate for conscious sedation Subjects who meet the following criteria will be considered eligible for randomization: * Documented daytime systolic ABP ≥ 135 mmHg and \< 180 mmHg after 4-week washout/run-in period.\*\* * Suitable renal anatomy compatible with the renal denervation procedure, documented by renal CTA or MRA of good quality performed within one year prior to consent (a CTA or MRA will be obtained in subjects without a recent (≤1 year) cross-sectional renal imaging). The renal angiogram procedure done in the cath lab prior to randomization will serve as the final anatomy compatibility check. * Potassium-sparing diuretics such as Amiloride hydrochloride and Triamterene may be prescribed in combination with another diuretic (e.g. a thiazide or loop diuretic) for their potassium conservation properties. In this situation, the diuretic combination is considered as a single class of anti-hypertensive.
Exclusion criteria
1. Subject has been previously diagnosed with abnormal renal artery anatomy and/or renal anatomy such as a single kidney, ectopic or horseshoe kidney, polycystic kidney disease, kidney tumors or other findings precluding renal denervation therapy as detailed in the angiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in average daytime ambulatory systolic BP | From baseline to 2 months post-procedure | Primary outcome |
| Subject level composite of the incidence of Major Adverse Events (MAE) | From Baseline to 30 day and 6 months post procedure | Safety outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in average office systolic BP | From baseline to 2 Months post procedure | Secondary outcome |
| Reduction in average daytime ambulatory diastolic BP | From baseline to 2 Months post procedure | Secondary outcome |
| Reduction in average 24-hr ambulatory diastolic BP | From baseline to 2 Months post procedure | Secondary outcome |
| Reduction in average home diastolic BP | From baseline to 2 Months post procedure | Secondary outcome |
| Reduction in average 24-hr ambulatory systolic BP | From baseline to 2 Months post procedure | Secondary outcome |
| Percentage of subjects with Systolic Blood Pressure (SBP) at target (daytime SBP <135 mmHg; office SBP <140 | From baseline to 2 and 6 Months post procedure | Secondary outcome |
| Incidence of ambulatory systolic BP (daytime/24-hr/night-time) reductions of ≥5 mmHg, ≥10 mmHg, and ≥15 mm Hg | From baseline to 2, 6, and 12 Months post procedure | Secondary outcome |
| Percentage of subjects with SBP at target (daytime SBP <135 mmHg; office SBP <140 mmHg) in the absence of. changes in hypertensive medication in each arm | From baseline to 2 and 6 Months post procedure | Secondary outcome |
| Reduction in average office diastolic BP | From baseline to 2 Months post procedure | Secondary outcome |
| Reduction in average home systolic BP | From baseline to 2 Months post procedure | Secondary outcome |
Countries
France, Germany, Greece, Italy, United States
Contacts
CONTACTLisa Melchior
CONTACTJanelle Noble
STUDY_CHAIRAjay Kirtane, MD
Columbia University
STUDY_CHAIRMichel Azizi, MD
George Pompidou Hospital
STUDY_CHAIRFelix Mahfoud, MD
University of Basel
Outcome results
None listed