Catheter-Based Renal Denervation for Resistant Hypertension
Catheter-Based Renal Denervation for Resistant Hypertension
SYMPLICITY HTN-2 enrolled subjects from June 2009 to January 2010 at 24 clinical sites in Europe, Australia, and New Zealand. The trial was approved by the local Ethics Committees in accordance with the Declaration of Helsinki and all subjects provided written informed consent.
Details of the trial methods have been previously reported. In summary, hypertensive adult subjects with a systolic blood pressure (SBP) ≥160 mmHg (≥150 mmHg if they had type-2 diabetes mellitus) while receiving ≥3 antihypertensive medications were eligible for randomization in the trial. Exclusion criteria included a history of a prior renal artery intervention, main renal arteries <4 mm in diameter, or <20 mm in length and haemodynamically or anatomically significant renal artery abnormalities. The baseline estimated glomerular filtration rate (eGFR) was required to be >45 mL/min/1.73 m as calculated by the Modification of Diet in Renal Disease formula. Subjects with type 1 diabetes mellitus and stenotic valvular heart disease, or myocardial infarction, unstable angina, or cerebrovascular accident within 6 months prior to enrolment were also excluded.
All the subjects underwent a 2-week screening period both before randomization and before their 6-month follow-up to establish adherence to a stable pharmacological treatment regimen and to confirm that SBP was ≥160 mmHg. Subjects were asked to record medications in a diary for 2 weeks at baseline and again at 6-month post-randomization. Control subjects, however, were not required to keep a diary again before the 6-month measurement post-RDN treatment. The study did not include any dietary recommendations. Physicians were encouraged to maintain subjects on a stable drug regimen throughout the study period, although clinically necessary modifications of drug choice or dose were allowed. All the subjects underwent renal artery imaging (renal duplex, computed tomography, MRI, or angiogram) before randomization to establish anatomical eligibility. Among the 190 subjects assessed for eligibility, 84 subjects were excluded from eligibility, and 106 were randomly allocated 1 : 1 to the RDN group (n = 52) or control group (n = 54) (Appendix Figure 1). The RDN procedure has been previously described. Neither study personnel nor subjects were blinded to the study group allocation. At the 6-month follow-up visit, control group subjects were eligible to crossover to receive RDN treatment. The treated crossover group reported here had a SBP ≥160 mmHg (≥150 mmHg in subjects with type II diabetes mellitus) at the 6-month visit. Control group subjects (n = 9) with a SBP <160 mmHg (<150 mmHg in subjects with type II diabetes mellitus) at the 6-month visit who chose to proceed to RDN on compassionate grounds are excluded from the present blood pressure analysis but are included in the safety analysis. Participating study sites, where subjects were treated, were designated European hypertension centres of excellence in 16 of 24 instances.
(Enlarge Image)
Figure A1.
Study randomization, 24-h ambulatory blood pressure measurement, ABPM; month, mo; week, wk; systolic blood pressure, SBP; classes of antihypertensive medications, meds; magnetic resonance angiography, MRA; computed tomography angiography, CTA; duplex ultrasonography, duplex.
Descriptive statistics were used to present results for the initial RDN and crossover groups. Comparisons of blood pressure and heart rate measurements at trial milestones were compared with pre-procedure measurements using the paired t-test. A change was considered significant if the two-side alpha level was ≤0.05. Variability of office blood pressure in all follow-up visits was calculated as the standard deviation (SD) or coefficient of variation (%, 100 * SD/mean). Between group differences were compared using confidence intervals and tested using unpaired t-tests. Statistical analyses were performed using SAS version 9.2.
Methods
Study Population and Protocol
SYMPLICITY HTN-2 enrolled subjects from June 2009 to January 2010 at 24 clinical sites in Europe, Australia, and New Zealand. The trial was approved by the local Ethics Committees in accordance with the Declaration of Helsinki and all subjects provided written informed consent.
Details of the trial methods have been previously reported. In summary, hypertensive adult subjects with a systolic blood pressure (SBP) ≥160 mmHg (≥150 mmHg if they had type-2 diabetes mellitus) while receiving ≥3 antihypertensive medications were eligible for randomization in the trial. Exclusion criteria included a history of a prior renal artery intervention, main renal arteries <4 mm in diameter, or <20 mm in length and haemodynamically or anatomically significant renal artery abnormalities. The baseline estimated glomerular filtration rate (eGFR) was required to be >45 mL/min/1.73 m as calculated by the Modification of Diet in Renal Disease formula. Subjects with type 1 diabetes mellitus and stenotic valvular heart disease, or myocardial infarction, unstable angina, or cerebrovascular accident within 6 months prior to enrolment were also excluded.
All the subjects underwent a 2-week screening period both before randomization and before their 6-month follow-up to establish adherence to a stable pharmacological treatment regimen and to confirm that SBP was ≥160 mmHg. Subjects were asked to record medications in a diary for 2 weeks at baseline and again at 6-month post-randomization. Control subjects, however, were not required to keep a diary again before the 6-month measurement post-RDN treatment. The study did not include any dietary recommendations. Physicians were encouraged to maintain subjects on a stable drug regimen throughout the study period, although clinically necessary modifications of drug choice or dose were allowed. All the subjects underwent renal artery imaging (renal duplex, computed tomography, MRI, or angiogram) before randomization to establish anatomical eligibility. Among the 190 subjects assessed for eligibility, 84 subjects were excluded from eligibility, and 106 were randomly allocated 1 : 1 to the RDN group (n = 52) or control group (n = 54) (Appendix Figure 1). The RDN procedure has been previously described. Neither study personnel nor subjects were blinded to the study group allocation. At the 6-month follow-up visit, control group subjects were eligible to crossover to receive RDN treatment. The treated crossover group reported here had a SBP ≥160 mmHg (≥150 mmHg in subjects with type II diabetes mellitus) at the 6-month visit. Control group subjects (n = 9) with a SBP <160 mmHg (<150 mmHg in subjects with type II diabetes mellitus) at the 6-month visit who chose to proceed to RDN on compassionate grounds are excluded from the present blood pressure analysis but are included in the safety analysis. Participating study sites, where subjects were treated, were designated European hypertension centres of excellence in 16 of 24 instances.
(Enlarge Image)
Figure A1.
Study randomization, 24-h ambulatory blood pressure measurement, ABPM; month, mo; week, wk; systolic blood pressure, SBP; classes of antihypertensive medications, meds; magnetic resonance angiography, MRA; computed tomography angiography, CTA; duplex ultrasonography, duplex.
Statistical Analysis
Descriptive statistics were used to present results for the initial RDN and crossover groups. Comparisons of blood pressure and heart rate measurements at trial milestones were compared with pre-procedure measurements using the paired t-test. A change was considered significant if the two-side alpha level was ≤0.05. Variability of office blood pressure in all follow-up visits was calculated as the standard deviation (SD) or coefficient of variation (%, 100 * SD/mean). Between group differences were compared using confidence intervals and tested using unpaired t-tests. Statistical analyses were performed using SAS version 9.2.
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