Renal Denervation for Management of Drug-Resistant Hypertension
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional

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.
    

Intervention name(s): Renal denervation
Intervention type(s): Procedure
Intervention description(s): Renal denervation in the intervention group
Other intervention name(s): Renal denervation, using an intravascular catheter system
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel group trial
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Treatment-resistant hypertension; Renal denervation; Sympathetic nervous system