Phase II randomized sham-controlled study of renal denervation for individuals with uncontrolled hypertension – WAVE IV

Schmieder, Roland E.; Ott, Christian; Toennes, Stefan W.; Bramlage, Peter; Gertner, Michael; Dawood, Omar Thanoon; Baumgart, Peter; O’Brien, Benjamin; Dasgupta, Indranil; Nickenig, Georg; Ormiston, John A.; Saxena, Manish; Sharp, Andrew; Sievert, Horst; Špinar, Jindřich; Stárek, Zdeněk; Weil, Joachim; Wenzel, Ulrich; Witkowski, Adam; Lobo, Melvin D.

doi:10.1097/hjh.0000000000001584

Cited by 57 publications

(25 citation statements)

References 31 publications

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“…Reasons for the failure of external ultrasound RDN to provide a significant reduction in BP over and above sham therapy have been previously described 17. It would be reasonable to propose that this novel technology actually did not achieve renal denervation based upon the BP response alone, but 2 lines of evidence support the hypothesis that renal nerve ablation did occur following active therapy in our study.…”

Section: Discussionsupporting

confidence: 70%

“…This study is a single‐center substudy of the Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension study, an international, multicenter, randomized, sham‐controlled, double‐blind clinical trial of RDN in subjects with treatment‐resistant hypertension 17. The study had approval from a Central Research Ethics Committee and all participants gave written informed consent to take part in the main study and the substudy.…”

Section: Methodsmentioning

confidence: 99%

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Attenuation of Splanchnic Autotransfusion Following Noninvasive Ultrasound Renal Denervation: A Novel Marker of Procedural Success

Saxena

Shour

Shah

et al. 2018

JAHA

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BackgroundRenal denervation has no validated marker of procedural success. We hypothesized that successful renal denervation would reduce renal sympathetic nerve signaling demonstrated by attenuation of α‐1‐adrenoceptor‐mediated autotransfusion during the Valsalva maneuver.Methods and ResultsIn this substudy of the Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension, we enrolled 23 subjects with resistant hypertension. They were randomized either to bilateral renal denervation using therapeutic levels of ultrasound energy (n=12) or sham application of diagnostic ultrasound (n=11). Within‐group changes in autonomic parameters, office and ambulatory blood pressure were compared between baseline and 6 months in a double‐blind manner. There was significant office blood pressure reduction in both treatment (16.1±27.3 mm Hg, P<0.05) and sham groups (27.9±15.0 mm Hg, P<0.01) because of which the study was discontinued prematurely. However, during the late phase II (Iii) of Valsalva maneuver, renal denervation resulted in substantial and significant reduction in mean arterial pressure (21.8±25.2 mm Hg, P<0.05) with no significant changes in the sham group. Moreover, there were significant reductions in heart rate in the actively treated group at rest (6.0±11.5 beats per minute, P<0.05) and during postural changes (supine 7.2±8.4 beats per minute, P<0.05, sit up 12.7±16.7 beats per minute, P<0.05), which were not observed in the sham group.ConclusionsBlood pressure reduction per se is not necessarily a marker of successful renal nerve ablation. Reduction in splanchnic autotransfusion following renal denervation has not been previously demonstrated and denotes attenuation of (renal) sympathetic efferent activity and could serve as a marker of procedural success.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02029885.

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Section: Discussionsupporting

confidence: 70%

Section: Methodsmentioning

confidence: 99%

Attenuation of Splanchnic Autotransfusion Following Noninvasive Ultrasound Renal Denervation: A Novel Marker of Procedural Success

Saxena

Shour

Shah

et al. 2018

JAHA

Self Cite

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“…However, HIFU requires good quality images to visualise the target, which may be difficult in overweight patients. Although initial clinical evaluation using HIFU reported effectiveness in office BP reduction, the recently published randomised sham-controlled WAVE IV study showed no difference in office or 24-hour ambulatory BP reduction between the RAD and the sham control arms at 24 weeks [48,52].…”

Section: Ultrasound (Us)mentioning

confidence: 95%

Renal Artery Denervation in Resistant Hypertension: The Good, The Bad and The Future

Raisi

Pouliopoulos

Swinnen

et al. 2020

Heart, Lung and Circulation

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“…The decreases in systolic pressure in the denervation (n = 364) compared with the control (n = 171) group were 14.1 mmHg vs. 11.7 mmHg and 6.8 mmHg vs. 4.8 mmHg on office and ambulatory monitoring, respectively, resulting in baseline-adjusted intergroup differences of 2.4 mmHg (95% CI 2.1-6.9 mmHg; p = 0.26) and 2.0 mmHg (95% CI -1.0-5.0 mmHg; p = 0.98) [60]. SYMPLICTY HTN-3 [60] and other trials reporting similarly disappointing [37,[61][62][63][64][65][66] or borderline significant [67] results, even if all of them confirmed the safety of the procedure, shattered the prospect of bringing renal denervation to clinical application in treatment-resistant hypertension (Fig. 2).…”

Section: Device-based Treatmentmentioning

confidence: 98%

“…2), only WAVE IV (NCT02029885) [66] applied externally delivered ultrasound energy to sever the renal nerves. All other trials [37,38,[58][59][60][61][62][63][64][65][66] used an intraarterial approach to deliver radiofrequency energy. A randomised trial using intravascularly delivered ultrasound energy is ongoing (RADIANCE-HTN; NCT02649426) and expected to report in 2018.…”

Section: Device-based Treatmentmentioning

confidence: 99%

Resistant hypertension

Wei¹,

Zhang²,

Huang³

et al. 2018

Kardiol Pol

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The publication of the first non-randomised proof-of-concept trial of renal denervation as a treatment modality in treatment- -resistant hypertension set the stage for a search for novel devices with the expectation that technology would reduce the burden of hypertension by reducing or eliminating the costly and lifelong use of blood pressure-lowering medications. As we demonstrate in this review, this idea was so attractive to manufacturers and invasive cardiologists and radiologists that they overlooked decades of careful pathophysiological research in a disease that remains enigmatic but is still a major cause of cardio-vascular mortality worldwide. To make our point, we first reviewed the prevalence and risks associated with treatment-resistant hypertension. Next, we highlighted the key points required for the diagnosis of treatment-resistant hypertension, including the recording of ambulatory blood pressure and the assessment of adherence to medication. Finally, we summarised new insights in the management of treatment-resistant hypertension by medication and devices as well as in future research. Throughout our review, we focused on new evidence that had become available since 2013. Our conclusion is that optimising medical treatment based on simple algorithms remains the state of the art in treatment-resistant hypertension.

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Phase II randomized sham-controlled study of renal denervation for individuals with uncontrolled hypertension – WAVE IV

Abstract: Our data did not prove that antihypertensive efficacy of the externally delivered focused ultrasound for RDN was greater than the sham effect. Stabilization of BP at baseline was identified as an important determinant of BP changes.

Cited by 57 publications

References 31 publications

Attenuation of Splanchnic Autotransfusion Following Noninvasive Ultrasound Renal Denervation: A Novel Marker of Procedural Success

Attenuation of Splanchnic Autotransfusion Following Noninvasive Ultrasound Renal Denervation: A Novel Marker of Procedural Success

Renal Artery Denervation in Resistant Hypertension: The Good, The Bad and The Future

Resistant hypertension

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