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C Fenton - One of the best experts on this subject based on the ideXlab platform.
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lumber facet joint injection in treating low back pain radiofrequency denervation versus Sham Procedure
Orthopaedic Proceedings, 2018Co-Authors: M Alnajjim, C FentonAbstract:AimsA systematic review of the available literature comparing the outcomes of radiofrequency denervation to Sham Procedure in treating chronic low back pain caused by lumber zygapophysial joint pathology.MethodsMedline and EMBASE databases were searched for English language articles from 2005 to July 2010. Articles were considered for review if they satisfied the inclusion criteria: Randomised Controlled Trials(RCT) comparing radiofrequency neurotomy(RFN) to a ‘placebo’ Procedure in patients with chronic low back pain caused by facet joint osteoarthritis. Adult patients of both sexes above 17 years of age who complained of continuous low back pain for more than 6 months with focal tenderness over the facet joints. Outcome measures of interest are pain improvement, physical activity, analgesic use, quality of life variables, range of motion of the lumbar spine and hip movement.Critical appraisal of the selected studies was carried out using the CASP appraisal tool for RCT.ResultsTwo articles were identifie...
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lumber facet joint injection in treating low back pain radiofrequency denervation versus Sham Procedure
Journal of Bone and Joint Surgery-british Volume, 2013Co-Authors: M Alnajjim, C FentonAbstract:Aims A systematic review of the available literature comparing the outcomes of radiofrequency denervation to Sham Procedure in treating chronic low back pain caused by lumber zygapophysial joint pathology. Methods Medline and EMBASE databases were searched for English language articles from 2005 to July 2010. Articles were considered for review if they satisfied the inclusion criteria: Randomised Controlled Trials(RCT) comparing radiofrequency neurotomy(RFN) to a ‘placebo’ Procedure in patients with chronic low back pain caused by facet joint osteoarthritis. Adult patients of both sexes above 17 years of age who complained of continuous low back pain for more than 6 months with focal tenderness over the facet joints. Outcome measures of interest are pain improvement, physical activity, analgesic use, quality of life variables, range of motion of the lumbar spine and hip movement. Critical appraisal of the selected studies was carried out using the CASP appraisal tool for RCT. Results Two articles were identified. Both demonstrated a statistically significant improvement in the pain (p Conclusion Radiofrequency denervation is better than Sham Procedure in treating pain caused by facet joint osteoarthritis with minimal adverse effects in the short term. A higher powered trial using a larger cohort and longer follow up is required to resolve some of the equivocal results. Conflicts of Interest None Source of Funding None
Sarah Gheuens - One of the best experts on this subject based on the ideXlab platform.
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An Integrated Safety Analysis of Infants and Children with Symptomatic Spinal Muscular Atrophy (SMA) Treated with Nusinersen in Seven Clinical Trials
CNS Drugs, 2019Co-Authors: Basil T Darras, Richard S. Finkel, Michelle A. Farrar, Eugenio Mercuri, Richard Foster, Steven G. Hughes, Ishir Bhan, Wildon Farwell, Sarah GheuensAbstract:Background Treatment with nusinersen has demonstrated significant and clinically meaningful benefits in clinical trials in infants and children with spinal muscular atrophy (SMA). Objective The objective of this analysis was to characterize the safety of nusinersen across the clinical trial program in infants and children with symptomatic SMA. Methods An integrated safety analysis evaluated end of study data from seven completed clinical trials that enrolled infants and children with symptomatic SMA who were treated with intrathecal nusinersen or underwent Sham Procedures. Two of the studies were conducted in symptomatic infants with infantile-onset SMA (most likely to develop SMA type I or II) and the remaining five in symptomatic children and adolescents with later-onset SMA (have or are most likely to develop SMA type II or III). Safety assessments included incidence of adverse events (AEs), physical and neurological examinations, vital signs, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and electrocardiograms. Results Data were analyzed from 323 infants and children, including 240 treated with nusinersen (100 with infantile-onset SMA and 140 with later-onset SMA) and 83 who underwent Sham Procedures (41 infantile-onset, 42 later-onset). Median (range) exposure to nusinersen was 449.0 (6–1538) days (375.9 participant-years). The most common AEs with nusinersen were pyrexia, upper respiratory tract infection, nasopharyngitis, vomiting, headache, and constipation. The incidence of serious AEs was lower with nusinersen than with the Sham Procedure (41% vs. 61%). The overall incidence of respiratory, thoracic, and mediastinal AEs was higher in participants with symptomatic infantile-onset SMA than those with symptomatic later-onset SMA and similar in nusinersen- versus Sham Procedure–treated participants. Rates of post–lumbar puncture syndrome and related events were higher with nusinersen versus Sham Procedure in later-onset SMA participants. No abnormal patterns or trends in laboratory test results were observed. Conclusions Nusinersen demonstrated a favorable safety profile in children with symptomatic infantile- and later-onset SMA. Most reported AEs and serious AEs were consistent with the nature and frequency of events typically seen with SMA or in the context of lumbar puncture Procedures. Registration NCT01494701, NCT01703988, NCT01839656, NCT02193074, NCT02292537, NCT01780246, NCT02052791.
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an integrated safety analysis of infants and children with symptomatic spinal muscular atrophy sma treated with nusinersen in seven clinical trials
CNS Drugs, 2019Co-Authors: Basil T Darras, Richard S. Finkel, Michelle A. Farrar, Eugenio Mercuri, Richard Foster, Steven G. Hughes, Ishir Bhan, Wildon Farwell, Sarah GheuensAbstract:Treatment with nusinersen has demonstrated significant and clinically meaningful benefits in clinical trials in infants and children with spinal muscular atrophy (SMA). The objective of this analysis was to characterize the safety of nusinersen across the clinical trial program in infants and children with symptomatic SMA. An integrated safety analysis evaluated end of study data from seven completed clinical trials that enrolled infants and children with symptomatic SMA who were treated with intrathecal nusinersen or underwent Sham Procedures. Two of the studies were conducted in symptomatic infants with infantile-onset SMA (most likely to develop SMA type I or II) and the remaining five in symptomatic children and adolescents with later-onset SMA (have or are most likely to develop SMA type II or III). Safety assessments included incidence of adverse events (AEs), physical and neurological examinations, vital signs, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and electrocardiograms. Data were analyzed from 323 infants and children, including 240 treated with nusinersen (100 with infantile-onset SMA and 140 with later-onset SMA) and 83 who underwent Sham Procedures (41 infantile-onset, 42 later-onset). Median (range) exposure to nusinersen was 449.0 (6–1538) days (375.9 participant-years). The most common AEs with nusinersen were pyrexia, upper respiratory tract infection, nasopharyngitis, vomiting, headache, and constipation. The incidence of serious AEs was lower with nusinersen than with the Sham Procedure (41% vs. 61%). The overall incidence of respiratory, thoracic, and mediastinal AEs was higher in participants with symptomatic infantile-onset SMA than those with symptomatic later-onset SMA and similar in nusinersen- versus Sham Procedure–treated participants. Rates of post–lumbar puncture syndrome and related events were higher with nusinersen versus Sham Procedure in later-onset SMA participants. No abnormal patterns or trends in laboratory test results were observed. Nusinersen demonstrated a favorable safety profile in children with symptomatic infantile- and later-onset SMA. Most reported AEs and serious AEs were consistent with the nature and frequency of events typically seen with SMA or in the context of lumbar puncture Procedures. NCT01494701, NCT01703988, NCT01839656, NCT02193074, NCT02292537, NCT01780246, NCT02052791.
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safety and efficacy of nusinersen in infants children with spinal muscular atrophy sma part 1 of the phase 2 embrace study p2 324
Neurology, 2018Co-Authors: Perry B Shieh, Gyula Acsadi, Thomas O Crawford, Randal Richardson, Diana Castro, Ishir Bhan, Sarah Gheuens, W Muellerfelber, Nina Natarajan, Giulia GambinoAbstract:Objective: EMBRACE (NCT02462759) Part 1 is a phase 2, double-blind, Sham-Procedure controlled study assessing the safety/tolerability of intrathecal nusinersen in symptomatic infants/children with spinal muscular atrophy (SMA) who were not eligible to participate in the ENDEAR or CHERISH studies. Background: Nusinersen is an antisense oligonucleotide that modulates splicing of SMN2 precursor mRNA that has demonstrated clinically meaningful efficacy and a favorable benefit-risk profile across SMA populations. Design/Methods: Eligible participants had genetic documented 5qSMA (homozygous SMN1 gene deletion, mutation, or compound heterozygote) and either onset of signs/symptoms consistent with SMA at ≤6 months with 3 SMN2 gene copies; or onset at ≤6 months, >7 months at screening, and 2 SMN2 gene copies; or onset at >6 months, ≤18 months at screening, and 2/3 SMN2 gene copies. Participants were randomized (2:1) to 12-mg equivalent dose nusinersen or Sham-Procedure and stratified by age at onset >6 vs ≤6 months. Safety/tolerability was the primary endpoint. Exploratory efficacy endpoints included Hammersmith Infant Neurological Examination (HINE) Section 2 motor milestone attainment, change in ventilator use, and growth parameters. Results: EMBRACE Part 1 was terminated early based on positive results from the phase 3 ENDEAR (NCT02193074) study. The safety/tolerability profile of nusinersen in EMBRACE was similar to that observed in previous trials. A larger proportion of nusinersen-treated (11/14; 79%) vs. Sham Procedure–treated individuals (2/7; 29%) were HINE motor milestone responders. Between the Day 183 and 302 visits, hours of ventilator use changed by a mean (SD) of +1.236 (3.712) hours in nusinersen-treated individuals (n=12) and by +2.123 (3.023) hours in Sham Procedure–treated individuals (n=7). Similar increases in weight and body length over time were observed in nusinersen-treated and Sham Procedure–treated individuals by Day 183. Conclusions: In EMBRACE Part 1 nusinersen demonstrated a favorable benefit-risk profile. These results add to the aggregated efficacy, safety/tolerability data of nusinersen in SMA. Study Supported by: Ionis Pharmaceuticals, Inc. (Carlsbad, CA, USA) and Biogen (Cambridge, MA, USA). Disclosure: Dr. Shieh has nothing to disclose. Dr. Acsadi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for Avexis, Biogen, Genentech and Serepta. Dr. Mueller-Felber has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for AveXis and Biogen. Dr. Mueller-Felber has received research support from clinical trial research contracts with Biogen, Santhera and Sarepta. Dr. Crawford has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisor/consultant for AveXis, Biogen, Catalyst, Cure SMA, Cytokinetics, Marathon, Novartis, Roche, Sarepta and the Spinal Muscular Atrophy Foundation. Dr. Richardson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for Biogen. Dr. Richardson has received research support from clinical trial research contracts with Biogen. Dr. Natarajan has received research support from Clinical trial research contract with Biogen. Dr. Castro has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Sarepta and Marathon. Dr. Gheuens has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Bhan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Bhan holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Gambino has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Gambino holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Sun has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Sun holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Farwell has nothing to disclose. Dr. Reyna has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Reyna holds stock and/or stock options in Holds stock/stock options in Biogen.
M Azizi - One of the best experts on this subject based on the ideXlab platform.
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ultrasound renal denervation for hypertension resistant to a triple medication pill radiance htn trio a randomised multicentre single blind Sham controlled trial
The Lancet, 2021Co-Authors: M Azizi, Kintur Sanghvi, Manish Saxena, Philippe Gosse, John P Reilly, Terry Levy, Lars C Rump, Alexandre PersuAbstract:Summary Background Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. Methods In a randomised, international, multicentre, single-blind, Sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18–75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a Sham Procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov , NCT02649426 . Findings Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a Sham Procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the Sham Procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the Sham Procedure (−8·0 mm Hg [IQR –16·4 to 0·0] vs –3·0 mm Hg [–10·3 to 1·8]; median between-group difference –4·5 mm Hg [95% CI –8·5 to –0·3]; adjusted p=0·022); the median between-group difference was –5·8 mm Hg (95% CI –9·7 to –1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. Interpretation Compared with a Sham Procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. Funding ReCor Medical.
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six month results of treatment blinded medication titration for hypertension control after randomization to endovascular ultrasound renal denervation or a Sham Procedure in the radiance htn solo trial
Circulation, 2019Co-Authors: M Azizi, Roland E Schmieder, Felix Mahfoud, Michael A Weber, Joost Daemen, Melvin D Lobo, Andrew S P Sharp, Michael J BlochAbstract:Background: The multicenter, international, randomized, blinded, Sham-controlled RADIANCE-HTN SOLO trial (A Study of the ReCor Medical Paradise System in Clinical Hypertension) demonstrated a 6.3 m...
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endovascular ultrasound renal denervation to treat hypertension radiance htn solo a multicentre international single blind randomised Sham controlled trial
The Lancet, 2018Co-Authors: M Azizi, Roland E Schmieder, Felix Mahfoud, Michael A Weber, Joost Daemen, Justin E Davies, Jan N Basile, Ajay J KirtaneAbstract:Summary Background Early studies suggest that radiofrequency-based renal denervation reduces blood pressure in patients with moderate hypertension. We investigated whether an alternative technology using endovascular ultrasound renal denervation reduces ambulatory blood pressure in patients with hypertension in the absence of antihypertensive medications. Methods RADIANCE-HTN SOLO was a multicentre, international, single-blind, randomised, Sham-controlled trial done at 21 centres in the USA and 18 in Europe. Patients with combined systolic–diastolic hypertension aged 18–75 years were eligible if they had ambulatory blood pressure greater than or equal to 135/85 mm Hg and less than 170/105 mm Hg after a 4-week discontinuation of up to two antihypertensive medications and had suitable renal artery anatomy. Patients were randomised (1:1) to undergo renal denervation with the Paradise system (ReCor Medical, Palo Alto, CA, USA) or a Sham Procedure consisting of renal angiography only. The randomisation sequence was computer generated and stratified by centres with randomised blocks of four or six and permutation of treatments within each block. Patients and outcome assessors were blinded to randomisation. The primary effectiveness endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Patients were to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded. Major adverse events included all-cause mortality, renal failure, an embolic event with end-organ damage, renal artery or other major vascular complications requiring intervention, or admission to hospital for hypertensive crisis within 30 days and new renal artery stenosis within 6 months. This study is registered with ClinicalTrials.gov, number NCT02649426. Findings Between March 28, 2016, and Dec 28, 2017, 803 patients were screened for eligibility and 146 were randomised to undergo renal denervation (n=74) or a Sham Procedure (n=72). The reduction in daytime ambulatory systolic blood pressure was greater with renal denervation (−8·5 mm Hg, SD 9·3) than with the Sham Procedure (−2·2 mm Hg, SD 10·0; baseline-adjusted difference between groups: −6·3 mm Hg, 95% CI −9·4 to −3·1, p=0·0001). No major adverse events were reported in either group. Interpretation Compared with a Sham Procedure, endovascular ultrasound renal denervation reduced ambulatory blood pressure at 2 months in patients with combined systolic–diastolic hypertension in the absence of medications. Funding ReCor Medical.
M Alnajjim - One of the best experts on this subject based on the ideXlab platform.
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lumbar facet joint injection in treating low back pain radiofrequency denervation versus Sham Procedure systematic review
Journal of orthopaedics, 2018Co-Authors: M Alnajjim, Rohi Shah, Mahmoud Rahuma, Omar Abdul GabbarAbstract:The lumbar facet joints have been implicated as one of the causes of low-back pain syndromes. About 15-40% of patients who presented with chronic low-back pain was attributed to lumbar facet joint pain. The purpose of this study was to analyse whether radiofrequency denervation is better than Sham Procedure in treating chronic low-back pain caused by lumbar zygapophysial joints pathology. From the four identified randomised control trials, there is conflicting evidence at an intermediate 3-6-month stage, however; one study demonstrates statistical significance of radiofrequency denervation at 3 months. Longer-term follow-up is needed to prove the efficacy of radiofrequency denervation technique.
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lumber facet joint injection in treating low back pain radiofrequency denervation versus Sham Procedure
Orthopaedic Proceedings, 2018Co-Authors: M Alnajjim, C FentonAbstract:AimsA systematic review of the available literature comparing the outcomes of radiofrequency denervation to Sham Procedure in treating chronic low back pain caused by lumber zygapophysial joint pathology.MethodsMedline and EMBASE databases were searched for English language articles from 2005 to July 2010. Articles were considered for review if they satisfied the inclusion criteria: Randomised Controlled Trials(RCT) comparing radiofrequency neurotomy(RFN) to a ‘placebo’ Procedure in patients with chronic low back pain caused by facet joint osteoarthritis. Adult patients of both sexes above 17 years of age who complained of continuous low back pain for more than 6 months with focal tenderness over the facet joints. Outcome measures of interest are pain improvement, physical activity, analgesic use, quality of life variables, range of motion of the lumbar spine and hip movement.Critical appraisal of the selected studies was carried out using the CASP appraisal tool for RCT.ResultsTwo articles were identifie...
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lumber facet joint injection in treating low back pain radiofrequency denervation versus Sham Procedure
Journal of Bone and Joint Surgery-british Volume, 2013Co-Authors: M Alnajjim, C FentonAbstract:Aims A systematic review of the available literature comparing the outcomes of radiofrequency denervation to Sham Procedure in treating chronic low back pain caused by lumber zygapophysial joint pathology. Methods Medline and EMBASE databases were searched for English language articles from 2005 to July 2010. Articles were considered for review if they satisfied the inclusion criteria: Randomised Controlled Trials(RCT) comparing radiofrequency neurotomy(RFN) to a ‘placebo’ Procedure in patients with chronic low back pain caused by facet joint osteoarthritis. Adult patients of both sexes above 17 years of age who complained of continuous low back pain for more than 6 months with focal tenderness over the facet joints. Outcome measures of interest are pain improvement, physical activity, analgesic use, quality of life variables, range of motion of the lumbar spine and hip movement. Critical appraisal of the selected studies was carried out using the CASP appraisal tool for RCT. Results Two articles were identified. Both demonstrated a statistically significant improvement in the pain (p Conclusion Radiofrequency denervation is better than Sham Procedure in treating pain caused by facet joint osteoarthritis with minimal adverse effects in the short term. A higher powered trial using a larger cohort and longer follow up is required to resolve some of the equivocal results. Conflicts of Interest None Source of Funding None
Deepak L Bhatt - One of the best experts on this subject based on the ideXlab platform.
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Sham controlled randomized trials of catheter based renal denervation in patients with hypertension
Journal of the American College of Cardiology, 2019Co-Authors: Ajay J Kirtane, Deepak L Bhatt, Partha Sardar, Kevin F Kennedy, Saurav Chatterjee, Jay Giri, Peter A Soukas, William B WhiteAbstract:Abstract Background There are conflicting data regarding the relative effectiveness of renal sympathetic denervation (RSD) in patients with hypertension. Objectives The purpose of this study was to evaluate the blood pressure (BP) response after RSD in Sham-controlled randomized trials. Methods Databases were searched through June 30, 2018. Randomized trials (RCTs) with ≥50 patients comparing catheter-based RSD with a Sham control were included. The authors calculated summary treatment estimates as weighted mean differences (WMD) with 95% confidence intervals (CIs) using random-effects meta-analysis. Results The analysis included 977 patients from 6 trials. The reduction in 24-h ambulatory systolic blood pressure (ASBP) was significantly greater for patients treated with RSD than Sham Procedure (WMD −3.65 mm Hg, 95% CI: −5.33 to −1.98; p Conclusions RSD significantly reduced blood pressure compared with Sham control. Results of this meta-analysis should inform the design of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with hypertension.
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regression to the mean in symplicity htn 3 implications for design and reporting of future trials
Journal of the American College of Cardiology, 2016Co-Authors: Stuart J Pocock, Deepak L Bhatt, George L Bakris, Sandeep Brar, Martin Fahy, Bernard J GershAbstract:Regression to the mean (RTM) describes the tendency for an extreme measurement on 1 occasion to become less extreme when measured again. RTM may affect clinical trial data interpretation when the outcome measure has high variability. We investigated RTM in the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial of renal denervation versus a Sham Procedure. Analysis of covariance was performed on the 6-month change in systolic blood pressure, estimating a mean treatment difference of -4.11 mm Hg (95% confidence interval: -8.44 to 0.22 mm Hg; p = 0.064), which was similar to the unadjusted difference but with a smaller confidence interval. RTM occurred in both arms, but it had a negligible effect on the observed treatment difference. A second example concerns changes in hemoglobin A1c in a nonrandomized study. These findings emphasize the importance of incorporating RTM and analysis of covariance into the design and reporting of clinical studies of how treatments affect time changes in quantitative outcomes. (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261).
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a controlled trial of renal denervation for resistant hypertension
The New England Journal of Medicine, 2014Co-Authors: Deepak L Bhatt, David E Kandzari, John M Flack, Barry T Katzen, Martin B Leon, Laura Mauri, Manuela Negoita, Sidney Cohen, Suzanne Oparil, Krishna RochasinghAbstract:A total of 535 patients underwent randomization. The mean (±SD) change in systolic blood pressure at 6 months was −14.13±23.93 mm Hg in the denervation group as compared with −11.74±25.94 mm Hg in the Sham-Procedure group (P<0.001 for both comparisons of the change from baseline), for a difference of −2.39 mm Hg (95% confidence interval [CI], −6.89 to 2.12; P = 0.26 for superiority with a margin of 5 mm Hg). The change in 24-hour ambulatory systolic blood pressure was −6.75±15.11 mm Hg in the denervation group and −4.79±17.25 mm Hg in the Sham-Procedure group, for a difference of −1.96 mm Hg (95% CI, −4.97 to 1.06; P = 0.98 for superiority with a margin of 2 mm Hg). There were no significant differences in safety between the two groups. Conclusions This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a Sham control. (Funded by Medtronic; SYMPLICITY HTN-3 ClinicalTrials.gov number, NCT01418261.)