Renal Denervation for Management of Drug-Resistant Hypertension (INSPiRED)
This study is not yet open for participant recruitment.
Verified June 2013 by Katholieke Universiteit Leuven
Information provided by (Responsible Party):
Jan A. Staessen, Katholieke Universiteit Leuven
First received: January 3, 2012
Last updated: June 21, 2013
Last verified: June 2013
INSPiRED is a multicenter parallel-group trial comparing usual medical treatment (control group) or usual medical treatment plus renal denervation (intervention). In both groups adherence will be monitored both before randomization and during 36 months of follow-up.
Procedure: Renal denervation
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
||Investigator-Steered Project on Intravascular Renal Denervation for Management of Drug-Resistant Hypertension
Primary Outcome Measures:
- Decrease in systolic blood pressure on daytime ambulatory measurement [ Time Frame: The primary endpoint will be assessed at the end of follow-up (6 months). ] [ Designated as safety issue: No ]
The primary endpoint deals with efficacy of renal denervation with regard to controlling blood pressure on ambulatory measurement. It consists of the baseline-adjusted between-group difference in the decrease in systolic blood pressure in daytime (10:00-20:00 h) ambulatory recordings. Because automated blood pressure monitors will be used, the assessment of the primary endpoint is blind.
Secondary Outcome Measures:
- Proportion of patients whose 24-hour blood pressure is controlled [ Time Frame: This endpoint will be assessed at the end of follow-up . ] [ Designated as safety issue: No ]
The proportion of patients reaching and maintaining blood pressure control over the whole day, defined as a 24-hour blood pressure level below 130 mm Hg systolic and 80 mm Hg diastolic.
- Proportion of patients whose daytime ambulatory blood pressure is controlled [ Time Frame: This endpoint will be assessed at the end of follow-up . ] [ Designated as safety issue: No ]
The proportion of patients reaching and maintaining blood pressure control, defined as a daytime ambulatory blood pressure below 135 mm Hg systolic and 85 mm Hg diastolic or below 130 mm Hg or 80 mm Hg, respectively.
- Proportion of patients whose office blood pressure is controlled [ Time Frame: This endpoint will be assessed at the end of follow-up. ] [ Designated as safety issue: No ]
The proportion of patients reaching and maintaining blood pressure control on clinic measurement, defined as an office blood pressure below 140 mm Hg systolic and 90 mm Hg diastolic.
- The intensity of medical treatment [ Time Frame: This endpoint will be assessed at the end of follow-up . ] [ Designated as safety issue: No ]
The number and doses of blood-pressure lowering drugs in the 2 arms of the trial.
- Safety [ Time Frame: This endpoint will be assessed at the end of follow-up . ] [ Designated as safety issue: Yes ]
Acute procedural safety; chronic procedural safety: reduction of eGFR by less than 25% or new stenosis over 60% confirmed by renal arteriography angiogram at 6 months; Change in renal function as assessed from serial measurements of serum creatinine, eGFR, measured or estimated creatinine clearance, micro-albuminuria, and proteinuria.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||November 2015 (Final data collection date for primary outcome measure)
No Intervention: Control group
Standard antihypertensive drug treatment
Experimental: Intervention group
Renal denervation plus standard antihypertensive drug treatment
Procedure: Renal denervation
Renal denervation in the intervention group
Other Name: Renal denervation, using an intravascular catheter system
|Ages Eligible for Study:
||20 Years to 79 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Women and men are eligible. Women of reproductive age should apply effective contraception.
- Age ranges from 20 years (inclusive) to less than 80 years.
- Patients should have essential hypertension. Patients with primary hyperaldosteronism without adrenal tumor and not responsive to a tolerable dose of spironolactone are also eligible.
- The patient should be taking a stable drug regimen for at least 4 weeks of 3 or more antihypertensive medications from different classes, including a diuretic. All major drug classes, unless contraindicated, should have been tried in multiple combinations and at maximal tolerable doses. Unless contra-indicated or not tolerated, aldosterone receptor antagonists, such as spironolactone 25 to 50 mg per day should have been attempted for at least 4 weeks to improve blood pressure control in treatment-resistant patients.
- Under maximal therapy, the 24-h ambulatory blood pressure should be 130 mm Hg systolic or 80 mm Hg diastolic or higher.
- The patients should have adherence checked before randomization, but both patients and doctors will remain blinded to the results. Both adherent and nonadherent patients can be randomized.
- Patients should be willing to accept hospitalization to optimize antihypertensive drug treatment, if required.
- Patients should be willing to attend the clinical centers for visits for the full supervised follow-up of 36 months according to the schedule in this protocol and to participate in a continuing assessment of their adherence to drug treatment.
- Patients should provide written informed consent for randomization, the procedure of renal denervation and follow-up including arteriography.
The clinical context is suboptimal for renal denervation.
- Myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 6 months of the screening period, or widespread atherosclerosis with documented intravascular thrombosis or unstable plaques.
- Type-1 diabetes mellitus requiring multiple adjustments of treatment to maintain control or diabetes mellitus with recent hyperglycemic or hypoglycemic coma.
- Renal dysfunction defined as an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73m2, using the MDRD formula.
- Untreated sleep apnoea syndrome, which could benefit from positive airway pressure.
The anatomy of the renal arteries is suboptimal for renal denervation. The prevalence of multiple renal arteries is approximately 60% with no difference according to sex or laterality. The average length of the main renal artery is greater at the right side and in kidneys with a single artery. The exclusion criteria based on anatomy are as follows:
- One or both main renal arteries are less than 4 mm in diameter and/or less than 20 mm in length
- Stenosis or other anatomical abnormalities of a renal artery, which preclude safe catheterization or which qualify for percutaneous or surgical repair.
- A history of prior renal artery intervention, including balloon angioplasty or stenting.
- The patient is on a waiting list for elective surgery or for a cardiovascular intervention.
- The patients should not have any serious medical condition, which in the opinion of the investigator, may adversely affect safety, such as patients with clinically significant peripheral vascular disease, abdominal aortic aneurysm, bleeding disorders such as thrombocytopenia, hemophilia, or significant anemia, or arrhythmias such as atrial fibrillation.
- Patients with an unresolved history of alcohol or substance abuse or psychiatric illnesses.
- Patients should not participate in any other trial of an investigational drug or device.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01505010
|Cliniques Universitaires Saint-Luc
|Brussels, Belgium, BE-1200 |
|Universitair Ziekenhuis Gasthuisberg
|Leuven, Belgium, BE-3000 |
|Contact: Geert Maleux, MD, PhD +32-16-347766 email@example.com |
|Contact: Johan Vaninbroukx, MD, PhD +32-16-347766 firstname.lastname@example.org |
|Principal Investigator: Stefan Janssen, MD, PhD |
|Sub-Investigator: Pieter Evenepoel, MD, PhD |
|Sub-Investigator: Kathleen Claes, MD, PhD |
Katholieke Universiteit Leuven
||Jan A. Staessen, MD, PhD
||University of Leuven
Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhäger WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O'Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997 Sep 13;350(9080):757-64.
Fletcher AE, Bulpitt CJ, Thijs L, Tuomilehto J, Antikainen R, Bossini A, Browne J, Duggan J, Kawecka-Jaszcz K, Kivinen P, Sarti C, Terzoli L, Staessen JA; Syst-Eur Trial Investigators. Quality of life on randomized treatment for isolated systolic hypertension: results from the Syst-Eur Trial. J Hypertens. 2002 Oct;20(10):2069-79.
||Jan A. Staessen, Professor of Medicine, Katholieke Universiteit Leuven
History of Changes
|Other Study ID Numbers:
||INSPiRED, version 4.0
|Study First Received:
||January 3, 2012
||June 21, 2013
||Belgium: Institutional Review Board
Keywords provided by Katholieke Universiteit Leuven:
Sympathetic nervous system
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 10, 2014