Renal Denervation for Management of Drug-Resistant Hypertension

Not Applicable

Completed

Conditions: Hypertension

Interventions: Procedure: Renal denervation

Registration Number: NCT01505010

Lead Sponsor: KU Leuven

Brief Summary: 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.

Detailed Description: Objectives:

To compare the blood pressure lowering efficacy and safety of renal denervation vs. usual medical therapy. The primary endpoints for efficacy and safety are the baseline-adjusted between-group differences in 24-h systolic blood pressure and in glomerular filtration rate as estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Secondary endpoints for efficacy and safety include other indexes of blood pressure control and renal function, metabolic variables and morbidity and mortality. These endpoints will be assessed 6 months after randomization.

Trial design:

Randomized controlled trial with blinded assessment of the primary and secondary endpoints. The study consists of 6 stages. Supervised and nonsupervised follow-up refer to assessment of outcome at or outside the participating center, respectively.

* Screening involves checking eligibility and ruling out secondary hypertension.

* Run-in period of 3 months to optimize medical treatment and to assess adherence to treatment.

* Stratification and randomization Eligible patients will be stratified by center and age group (adults vs. elderly, 20-49 vs. 50-69 years) and randomized centrally in a one-to-one proportion to control or intervention.

* Renal sympathetic denervation in the intervention group, patients of the control group will be offered renal denervation after 6 months.

* Supervised follow-up at 1, 3 and 6 months after randomization.

* Long-term supervised or non-supervised follow-up of morbidity and mortality beyond 6 months and up to 3 years.

Sample size:

To detect a 10-mm Hg difference (SD 20 mm Hg) in systolic blood pressure between the randomized groups with a 2-sided P-value of 0.01 and 90% power in total 240 patients need to be randomized. Allowing 50% screening failures, 480 patients would have to be screened.

Assessment of adherence:

Adherence to treatment will be assessed by measurement of drugs or drug metabolites in biological fluids. Jung and coworkers developed a liquid chromatography-mass spectrometric method that allows detecting all antihypertensive drugs or their metabolites in a single urine sample. This obligatory approach will be implemented.

Assessment of quality of life Assessment of quality of life is compulsory at baseline and at each visit during the supervised follow-up, using the EuroQol 5D.

Assessment of sympathetic modulation:

heart rate variability (HRV) will be assessed at baseline and at the 6-month follow-up visit, based on 15 minutes ECG recordings. A software program, developed in LabVIEW by the group of Aubert et al. will be used.

Relevance:

INSPiRED differs from previous and ongoing studies in several aspects: (1) a stringent selection of patients; (2) drug optimization with assessment of adherence throughout the study; (3) out-of-the-office blood pressure for patient selection and follow-up; (4) state-of-the-art renal artery imaging by computerized tomographic angiography; (5) validation of urinary proteomic biomarkers to predict blood pressure responses and changes in renal function; (6) follow-up will be beyond 6 months up to 3 years; (7) use of heart rate variability and renal nerve stimulation to assess the completeness of renal denervation.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 17

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group	Renal denervation	Renal denervation plus standard antihypertensive drug treatment
Control group	Renal denervation	Standard antihypertensive drug treatment

Primary Outcome Measures

Name	Time	Method
Change in Systolic Blood Pressure From Baseline to 6 Months on 24-h Ambulatory Measurement (Follow-up Minus Baseline Measurement)	The primary endpoint has been assessed 6 months after randomization.	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 changes in 24-h systolic blood pressure. Because automated blood pressure monitors will be used, the assessment of the primary endpoint is blind.
Change in Glomerular Filtration Rate	This endpoint has been assessed 6 months after randomization.	The primary endpoint for safety of renal denervation is the baseline-adjusted between group difference in the change of glomerular filtration rate estimated by using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation.

Secondary Outcome Measures

Name	Time	Method
The Intensity of Medical Treatment	This endpoint will be assessed 6 months after randomization.	The number and doses of blood-pressure lowering drugs in the 2 arms of the trial.