Abstract
Background: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. Methods: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. Findings: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was −3·9 mm Hg (Bayesian 95% credible interval −6·2 to −1·6) and for office systolic blood pressure the difference was −6·5 mm Hg (−9·6 to −3·5). No major device-related or procedural-related safety events occurred up to 3 months. Interpretation: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. Funding: Medtronic.
| Original language | English |
|---|---|
| Pages (from-to) | 1444-1451 |
| Number of pages | 8 |
| Journal | The Lancet |
| Volume | 395 |
| Issue number | 10234 |
| DOIs | |
| State | Published - May 2 2020 |
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Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal) : a multicentre, randomised, sham-controlled trial. / Böhm, Michael; Kario, Kazuomi; Kandzari, David E.; Mahfoud, Felix; Weber, Michael A.; Schmieder, Roland E.; Tsioufis, Konstantinos; Pocock, Stuart; Konstantinidis, Dimitris; Choi, James W.; East, Cara; Lee, David P.; Ma, Adrian; Ewen, Sebastian; Cohen, Debbie L.; Wilensky, Robert; Devireddy, Chandan M.; Lea, Janice; Schmid, Axel; Weil, Joachim; Agdirlioglu, Tolga; Reedus, Denise; Jefferson, Brian K.; Reyes, David; D'Souza, Richard; Sharp, Andrew S.P.; Sharif, Faisal; Fahy, Martin; DeBruin, Vanessa; Cohen, Sidney A.; Brar, Sandeep; Townsend, Raymond R.; Akarca, Ertan; Allaqaband, Suhail; Andrikou, Eirini; Aoki, Jiro; Arnold, Ahran; Aronow, Herbert; Asami, Masahiko; Bachinsky, William; Barton, John; Bass, Kyle; Batson, Bryan; Bell, Chris; Bertolet, Barry; Bewarder, Yvonne; Bihlmaier, Karl; Binner, Christian; Bloom, Jason; Blossom, Benjamin; Brar, Somjot; Brown, Angela; Burke, Robert; Burke, Martin N.; Butler, Michael; Calhoun, William; Campbell, James; Carroll, Steve; Chapman, Neil; Chasen, Craig; Cheng, Shi Chi; Chia, Beth; Choksi, Nishit; Cohen, Jordana; Connolly, Niall; Contreras, Johanna; Cusack, Ronan; Dangas, George; David, Shukri; Davies, Justin; Dederer, Juliane; Denker, Matthew; Desch, Udo; Didangelos, Matthaios; Dienemann, Thomas; Dimitriadis, Kyriakos; Dorval, Jean François; Estess, John; Fan, Sarah; Fengler, Karl; Ferguson, Lee; Fudim, Marat; Fuster, Valentin; Garcia, Fidel; Garcia, Santiago; Garton, Alex; Gessler, Carl; Ghali, Magdi; Gummadi, Bharat; Gupta, Amit; Gutierrez, Antonio; Hardesty, Peggy; Hartung, Phillip; Haught, Walter H.; Haun, Yonghong; Hays, Sara; Helmreich, Wolfgang; Hill, Douglas; Hopper, Ingrid; Horiuchi, Yu; Hoshide, Satoshi; Howard, James; Ikeda, Wanda; Jan, Fued; Jauhar, Rajiv; Jay, Desmond; Johnson, James; Johnston, Thomas; Jones, Schuyler; Jung, Susanne; Kalos, Theodoros; Kanitkar, Mihar; Kannenkeril, Dennis; Kasiakogias, Alexandros; Kazziha, Samer; Keene, Daniel; Khitha, Jayant; Kikushima, Hosei; Kobayashi, Taisei; Komiyama, Kota; Komori, Takahiro; Kotter, John; Kouparanis, Antonios; Krasnow, Joshua; Kulenthiran, Saarraangan; Kumar, Sarwan; L'Allier, Philippe; Laney, Phillip; Lauder, Lucas; Lavoie, Marc A.; Lerche, Matthias; Linesky, Elena; Little, Nelson; Lomboy, Carl; Lucic, Jelena; Lurz, Philipp; Lynch, Shannon; Mansukhani, Prakash; McDuffie, Katie; McGrath, Brian; McLaurin, Brent; Meade, Ashley; Meraj, Perwaiz; Millenaar, Dominic; Moore, Naing; Mori, Fumiko; Munch, Phillip; Murphy, James; Murray, Jennifer; Nanjundappa, Aravinda; Ninomiya, Kai; Oba, Yusuke; O'Connor, Tim; Ogata, Yukiyo; Ogoyama, Yukako; Onsrud, Rachel; Ott, Christian; Padaliya, Bimal; Pagidipati, Neha; Patel, Manesh; Patel, Kiritkumar; Petteinidou, Emanouela; Porr, Wendy; Rao, Anjani; Razi, Rabia; Regan, Christopher; Remetz, Michael; Rizik, David; Robison, Monique; Rommel, Karl Philipp; Rosseel, Liesbeth; Rothstein, Marcos; Rough, Randolph; Saavedra, Jose; Saba, Souhell; Schwartz, Robert; Selcer, Shaun; Sen, Sayan; Sennott, Jacqueline; Shadman, Ramin; Shah, Samit; Shemin, Douglas; Shimizu, Hayato; Shimpo, Masahisa; Shishehbor, Mehdi; Shun-Shin, Matthew; Sierra, Francisco; Singh, Jasvindar; Singh, Avneet; Sirajeldin, Yassir; Skeik, Nedaa; Soliman, George; Statton, Sarah; Stehli, Julia; Steigerwalt, Susan; Striepe, Kristina; Stuck, Jason; Suppan, Markus; Svetkey, Laura; Takker, Ganpat; Tanabe, Kengo; Tanaka, Tetsu; Tomii, Daijiro; Torre, Sabino; Traverse, Jay; Tyson, Crystal; Vasquez, Alejandro; Velasquez, Enrique; Vemulapalli, Sreekanth; Waki, Hirotaka; Walton, Tony; Wang, Yale; Weber, Thomas; Wells, Bryan; Wilkins, Robert; Wright, Thomas; Yahagi, Kazuyuki; Yeung, Alan; Zadegan, Ray; Zeller, Thomas; Ziada, Khaled; Ziakas, Antonios; Zidar, David.
In: The Lancet, Vol. 395, No. 10234, 02.05.2020, p. 1444-1451.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal)
T2 - a multicentre, randomised, sham-controlled trial
AU - Böhm, Michael
AU - Kario, Kazuomi
AU - Kandzari, David E.
AU - Mahfoud, Felix
AU - Weber, Michael A.
AU - Schmieder, Roland E.
AU - Tsioufis, Konstantinos
AU - Pocock, Stuart
AU - Konstantinidis, Dimitris
AU - Choi, James W.
AU - East, Cara
AU - Lee, David P.
AU - Ma, Adrian
AU - Ewen, Sebastian
AU - Cohen, Debbie L.
AU - Wilensky, Robert
AU - Devireddy, Chandan M.
AU - Lea, Janice
AU - Schmid, Axel
AU - Weil, Joachim
AU - Agdirlioglu, Tolga
AU - Reedus, Denise
AU - Jefferson, Brian K.
AU - Reyes, David
AU - D'Souza, Richard
AU - Sharp, Andrew S.P.
AU - Sharif, Faisal
AU - Fahy, Martin
AU - DeBruin, Vanessa
AU - Cohen, Sidney A.
AU - Brar, Sandeep
AU - Townsend, Raymond R.
AU - Akarca, Ertan
AU - Allaqaband, Suhail
AU - Andrikou, Eirini
AU - Aoki, Jiro
AU - Arnold, Ahran
AU - Aronow, Herbert
AU - Asami, Masahiko
AU - Bachinsky, William
AU - Barton, John
AU - Bass, Kyle
AU - Batson, Bryan
AU - Bell, Chris
AU - Bertolet, Barry
AU - Bewarder, Yvonne
AU - Bihlmaier, Karl
AU - Binner, Christian
AU - Bloom, Jason
AU - Blossom, Benjamin
AU - Brar, Somjot
AU - Brown, Angela
AU - Burke, Robert
AU - Burke, Martin N.
AU - Butler, Michael
AU - Calhoun, William
AU - Campbell, James
AU - Carroll, Steve
AU - Chapman, Neil
AU - Chasen, Craig
AU - Cheng, Shi Chi
AU - Chia, Beth
AU - Choksi, Nishit
AU - Cohen, Jordana
AU - Connolly, Niall
AU - Contreras, Johanna
AU - Cusack, Ronan
AU - Dangas, George
AU - David, Shukri
AU - Davies, Justin
AU - Dederer, Juliane
AU - Denker, Matthew
AU - Desch, Udo
AU - Didangelos, Matthaios
AU - Dienemann, Thomas
AU - Dimitriadis, Kyriakos
AU - Dorval, Jean François
AU - Estess, John
AU - Fan, Sarah
AU - Fengler, Karl
AU - Ferguson, Lee
AU - Fudim, Marat
AU - Fuster, Valentin
AU - Garcia, Fidel
AU - Garcia, Santiago
AU - Garton, Alex
AU - Gessler, Carl
AU - Ghali, Magdi
AU - Gummadi, Bharat
AU - Gupta, Amit
AU - Gutierrez, Antonio
AU - Hardesty, Peggy
AU - Hartung, Phillip
AU - Haught, Walter H.
AU - Haun, Yonghong
AU - Hays, Sara
AU - Helmreich, Wolfgang
AU - Hill, Douglas
AU - Hopper, Ingrid
AU - Horiuchi, Yu
AU - Hoshide, Satoshi
AU - Howard, James
AU - Ikeda, Wanda
AU - Jan, Fued
AU - Jauhar, Rajiv
AU - Jay, Desmond
AU - Johnson, James
AU - Johnston, Thomas
AU - Jones, Schuyler
AU - Jung, Susanne
AU - Kalos, Theodoros
AU - Kanitkar, Mihar
AU - Kannenkeril, Dennis
AU - Kasiakogias, Alexandros
AU - Kazziha, Samer
AU - Keene, Daniel
AU - Khitha, Jayant
AU - Kikushima, Hosei
AU - Kobayashi, Taisei
AU - Komiyama, Kota
AU - Komori, Takahiro
AU - Kotter, John
AU - Kouparanis, Antonios
AU - Krasnow, Joshua
AU - Kulenthiran, Saarraangan
AU - Kumar, Sarwan
AU - L'Allier, Philippe
AU - Laney, Phillip
AU - Lauder, Lucas
AU - Lavoie, Marc A.
AU - Lerche, Matthias
AU - Linesky, Elena
AU - Little, Nelson
AU - Lomboy, Carl
AU - Lucic, Jelena
AU - Lurz, Philipp
AU - Lynch, Shannon
AU - Mansukhani, Prakash
AU - McDuffie, Katie
AU - McGrath, Brian
AU - McLaurin, Brent
AU - Meade, Ashley
AU - Meraj, Perwaiz
AU - Millenaar, Dominic
AU - Moore, Naing
AU - Mori, Fumiko
AU - Munch, Phillip
AU - Murphy, James
AU - Murray, Jennifer
AU - Nanjundappa, Aravinda
AU - Ninomiya, Kai
AU - Oba, Yusuke
AU - O'Connor, Tim
AU - Ogata, Yukiyo
AU - Ogoyama, Yukako
AU - Onsrud, Rachel
AU - Ott, Christian
AU - Padaliya, Bimal
AU - Pagidipati, Neha
AU - Patel, Manesh
AU - Patel, Kiritkumar
AU - Petteinidou, Emanouela
AU - Porr, Wendy
AU - Rao, Anjani
AU - Razi, Rabia
AU - Regan, Christopher
AU - Remetz, Michael
AU - Rizik, David
AU - Robison, Monique
AU - Rommel, Karl Philipp
AU - Rosseel, Liesbeth
AU - Rothstein, Marcos
AU - Rough, Randolph
AU - Saavedra, Jose
AU - Saba, Souhell
AU - Schwartz, Robert
AU - Selcer, Shaun
AU - Sen, Sayan
AU - Sennott, Jacqueline
AU - Shadman, Ramin
AU - Shah, Samit
AU - Shemin, Douglas
AU - Shimizu, Hayato
AU - Shimpo, Masahisa
AU - Shishehbor, Mehdi
AU - Shun-Shin, Matthew
AU - Sierra, Francisco
AU - Singh, Jasvindar
AU - Singh, Avneet
AU - Sirajeldin, Yassir
AU - Skeik, Nedaa
AU - Soliman, George
AU - Statton, Sarah
AU - Stehli, Julia
AU - Steigerwalt, Susan
AU - Striepe, Kristina
AU - Stuck, Jason
AU - Suppan, Markus
AU - Svetkey, Laura
AU - Takker, Ganpat
AU - Tanabe, Kengo
AU - Tanaka, Tetsu
AU - Tomii, Daijiro
AU - Torre, Sabino
AU - Traverse, Jay
AU - Tyson, Crystal
AU - Vasquez, Alejandro
AU - Velasquez, Enrique
AU - Vemulapalli, Sreekanth
AU - Waki, Hirotaka
AU - Walton, Tony
AU - Wang, Yale
AU - Weber, Thomas
AU - Wells, Bryan
AU - Wilkins, Robert
AU - Wright, Thomas
AU - Yahagi, Kazuyuki
AU - Yeung, Alan
AU - Zadegan, Ray
AU - Zeller, Thomas
AU - Ziada, Khaled
AU - Ziakas, Antonios
AU - Zidar, David
N1 - Funding Information: The trial is sponsored by Medtronic (Santa Rosa, CA, USA) and was designed in collaboration with the US Food and Drug Administration by the steering committee and sponsor. MB, FM, and SE are supported by the Deutsche Forschungsgemeinschaft (DFG, TTR 219, S-01, M-03, M-05). The manuscript was written by the lead author with significant contributions from the trial's executive committee and all co-authors. The funder assisted with figure and table generation, copy editing and formatting. We thank Beth Ferri and Jessica Dries-Devlin for editorial assistance; Laura Mauri for expert review of the manuscript; Manuela Negoita for contributions to trial design; Graeme Hickey for statistical analysis oversight; Denise Jones, Pamela McKenna, Daiki Yasuhara, and Marianne Wanten for clinical trial oversight. Funding Information: MB reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Vifor, Servier, Medtronic, and Novartis; and grants from Deutsche Forschungsgemeinschaft and AstraZeneca, all outside the submitted work. KK reports grants and personal fees from Omron Healthcare, Daiichi Sankyo, and Takeda Pharmaceutical; grants from A&D, Roche Diagnostics, Merck Sharp and Dohme, Astellas Pharma, Otsuka Holdings, Otsuka Pharmaceutical, Sanofi, Shionogi & Co, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma, Mitsubishi Tanabe Pharma, Teijin Pharma, Boehringer Ingelheim Japan, Pfizer Japan, Fukuda Denshi, Fukuda Lifetec, Fukuda Lifetec Kanto, Bristol-Myers Squibb, Mylan, Mochida Pharmaceutical, IQVIA Services Japan; and personal fees from Terumo Corporation and Idorsia Pharmaceuticals Japan, all outside the submitted work. DEK reports grants and personal fees from Medtronic and grants from Ablative Solutions, all outside the submitted work. FM reports grants and personal fees from Medtronic during the conduct of the study; grants from Deutsche Hochdruckliga, Deutsche Gesellschaft für Kardiologie, and Deutsche Forschungsgemeinschaft, grants and personal fees from Medtronic and ReCor, and personal fees from Bayer and Boehringer Ingelheim, outside the submitted work. MAW reports personal fees from Medtronic, Ablative Solutions, ReCor, and Boston Scientific, all outside the submitted work. RES reports grants and personal fees from Medtronic, Recor, and Ablative Solution, all during the conduct of the study. KT reports grants from Medtronic, Recordati, and St Jude Medical; personal fees from Medtronic, Abbott, Bayer, Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer, Mylan, Chiesi, Pharmanel, Sanofi, Vianex, Winmedica, and Elpen, and is a member of the ESC/ESH HTN Gls task force, all outside the submitted work. SP reports personal fees from Medtronic outside the submitted work. DK reports payments for work as a study investigator from Medtronic during the conduct of the study. JWC reports consulting fees from Medtronic outside the submitted work. DPL reports grants from and serves on the advisory board for Medtronic, outside the submitted work. SE reports personal fees from Medtronic, Recor, Bayer, Daiichi Sankyo, Novartis, AstraZeneca, Akcea Therapeutics, and Pfizer and support from the Deutsche Forschungsgemeinschaft (DFG, TTR 219, S-01, M-03, M-05), all outside the submitted work. CMD reports personal fees from Medtronic, ReCor Medical, Shockwave Medical, and Vascular Dynamics, all outside the submitted work. JW reports study compensation from Medtronic for Sana Klinik LÜbeck, Germany during the conduct of the study; and personal fees from Novartis, ReCor, Cardinal Health, Bayer, and AstraZeneca, all outside the submitted work. BKJ reports personal fees from Medtronic, outside the submitted work. ASPS reports personal fees from Medtronic and Recor Medical outside the submitted work. FS reports personal fees from Medtronic outside the submitted work and consultation fees from Medtronic during the conduct of the study. MF, VD, SAC, and SB are all employees and shareholders of Medtronic. RRT reports personal fees from Medtronic during the conduct of the study. All other authors declare no competing interests. Funding Information: The trial is sponsored by Medtronic (Santa Rosa, CA, USA) and was designed in collaboration with the US Food and Drug Administration by the steering committee and sponsor. MB, FM, and SE are supported by the Deutsche Forschungsgemeinschaft (DFG, TTR 219, S-01, M-03, M-05). The manuscript was written by the lead author with significant contributions from the trial's executive committee and all co-authors. The funder assisted with figure and table generation, copy editing and formatting. We thank Beth Ferri and Jessica Dries-Devlin for editorial assistance; Laura Mauri for expert review of the manuscript; Manuela Negoita for contributions to trial design; Graeme Hickey for statistical analysis oversight; Denise Jones, Pamela McKenna, Daiki Yasuhara, and Marianne Wanten for clinical trial oversight. Publisher Copyright: © 2020 Elsevier Ltd
PY - 2020/5/2
Y1 - 2020/5/2
N2 - Background: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. Methods: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. Findings: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was −3·9 mm Hg (Bayesian 95% credible interval −6·2 to −1·6) and for office systolic blood pressure the difference was −6·5 mm Hg (−9·6 to −3·5). No major device-related or procedural-related safety events occurred up to 3 months. Interpretation: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. Funding: Medtronic.
AB - Background: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. Methods: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. Findings: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was −3·9 mm Hg (Bayesian 95% credible interval −6·2 to −1·6) and for office systolic blood pressure the difference was −6·5 mm Hg (−9·6 to −3·5). No major device-related or procedural-related safety events occurred up to 3 months. Interpretation: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. Funding: Medtronic.
UR - http://www.scopus.com/inward/record.url?scp=85083822944&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(20)30554-7
DO - 10.1016/S0140-6736(20)30554-7
M3 - Article
C2 - 32234534
AN - SCOPUS:85083822944
VL - 395
SP - 1444
EP - 1451
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 10234
ER -