SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study

• ClinicalTrials.gov Identifier: NCT02439749
• Recruitment Status: Active, not recruiting
• First Posted: May 12, 2015
• Last Update Posted: February 15, 2021
• Sponsor: Medtronic Vascular
• Information provided by (Responsible Party): Medtronic Vascular

Tracking Information

• First Submitted Date: April 28, 2015
• First Posted Date: May 12, 2015
• Last Update Posted Date: February 15, 2021
• Actual Study Start Date: June 2015
• Actual Primary Completion Date: April 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 3, 2018)

• Acute and chronic safety by evaluating incidence of Major Adverse Events [ Time Frame: From baseline to 1 month post-procedure (6 months for new renal artery stenosis) ]
• Change in systolic blood pressure as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM) [ Time Frame: From baseline to 3 months post-procedure ]

Original Primary Outcome Measures (submitted: May 6, 2015)

• Acute and chronic safety by evaluating incidence of Major Adverse Events [ Time Frame: From baseline to 36 months post-procedure ]
• Change in systolic blood pressure as measured by 24-hour Ambulatory Blood Pressure Monitoring (ABPM) [ Time Frame: From baseline to 36 months post-procedure ]

Current Secondary Outcome Measures (submitted: July 3, 2018)

• Change in office systolic blood pressure [ Time Frame: From baseline to 36 months post-procedure ]
• Significant embolic event resulting in end-organ damage [ Time Frame: From baseline to 1 month post-procedure ]
• Renal artery perforation requiring intervention [ Time Frame: From baseline to 1 month post-procedure ]
• Renal artery dissection requiring intervention [ Time Frame: From baseline to 1 month post-procedure ]
• Vascular complications [ Time Frame: From baseline to 1 month post-procedure ]
• End-stage renal disease [ Time Frame: From baseline to 36 months post-procedure ]
• ≥40% decline in eGFR [ Time Frame: From baseline to 36 months post-procedure ]
• New myocardial infarction [ Time Frame: From baseline to 36 months post-procedure ]
• New stroke [ Time Frame: From baseline to 36 months post-procedure ]
• Renal artery re-intervention [ Time Frame: From baseline to 36 months post-procedure ]
• Major bleeding according to TIMI definition [ Time Frame: From baseline to 36 months post-procedure ]
• Increase in serum creatinine > 50% [ Time Frame: From baseline to 36 months post-procedure ]
• New renal artery stenosis > 70% [ Time Frame: From baseline to 36 months post-procedure ]
• Hospitalization for hypertensive crisis not related to confirmed nonadherence with medications or the protocol [ Time Frame: From baseline to 36 months post-procedure ]
• All-cause mortality [ Time Frame: From baseline to 36 month post-procedure ]
• Change in systolic blood pressure as measured by 24-hour ABPM [ Time Frame: From baseline to 36 month post-procedure ]
• Incidence of achieving target office systolic blood pressure (SBP <140 mmHg) [ Time Frame: From 1 month to 36 months post-procedure ]
• Change in office diastolic blood pressure [ Time Frame: From baseline to 36 months post-procedure ]
• Change in diastolic blood pressure as measured by 24-hour ABPM [ Time Frame: From baseline to 36 months post-procedure ]

Original Secondary Outcome Measures (submitted: May 6, 2015)

• Change in office systolic blood pressure [ Time Frame: From baseline to 36 months post-procedure ]
• Incidence of achieving target office systolic blood pressure (SBP<140 mmHg or <130 mmHg for patients with diabetes or renal disease) [ Time Frame: From 1 month to 36 months post-procedure ]
• Change in office diastolic blood pressure [ Time Frame: From baseline to 36 months post-procedure ]
• Change in diastolic blood pressure as measured by 24-hour ABPM [ Time Frame: From baseline to 36 months post-procedure ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study
• Official Title: Global Clinical Study of Renal Denervation With the Symplicity Spyral™ Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED)
• Brief Summary: The purpose of this study is to test the hypothesis that renal denervation decreases blood pressure and is safe when studied in the absence of antihypertensive medications.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment

Condition

• Hypertension
• Vascular Diseases
• Cardiovascular Diseases

Intervention

• Device: Symplicity Spyral™ multi-electrode renal denervation system
  After a renal angiography according to standard procedures, subjects remain blinded and are immediately treated with the renal denervation procedure after randomization.
  Other Names:

  • Renal angiography
  • Renal Denervation
• Procedure: Sham Procedure
  After a renal angiography according to standard procedures, subjects remain blinded and remain on the catheterization lab table for at least 20 minutes prior to introducer sheath removal.
  Other Name: Renal angiography

Study Arms

• Experimental: Renal Denervation
  Renal angiography and Renal Denervation (Symplicity Spyral™ multi-electrode renal denervation system)
  Intervention: Device: Symplicity Spyral™ multi-electrode renal denervation system
• Sham Comparator: Sham Procedure
  Renal angiography
  Intervention: Procedure: Sham Procedure

Publications *

• Böhm M, Kario K, Kandzari DE, Mahfoud F, Weber MA, Schmieder RE, Tsioufis K, Pocock S, Konstantinidis D, Choi JW, East C, Lee DP, Ma A, Ewen S, Cohen DL, Wilensky R, Devireddy CM, Lea J, Schmid A, Weil J, Agdirlioglu T, Reedus D, Jefferson BK, Reyes D, D'Souza R, Sharp ASP, Sharif F, Fahy M, DeBruin V, Cohen SA, Brar S, Townsend RR; SPYRAL HTN-OFF MED Pivotal Investigators. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. 2020 May 2;395(10234):1444-1451. doi: 10.1016/S0140-6736(20)30554-7. Epub 2020 Mar 29.
• Böhm M, Townsend RR, Kario K, Kandzari D, Mahfoud F, Weber MA, Schmieder RE, Tsioufis K, Hickey GL, Fahy M, DeBruin V, Brar S, Pocock S. Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design. Clin Res Cardiol. 2020 Mar;109(3):289-302. doi: 10.1007/s00392-020-01595-z. Epub 2020 Feb 7. Erratum in: Clin Res Cardiol. 2020 May;109(5):653.
• Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, Ewen S, Tsioufis K, Tousoulis D, Sharp ASP, Watkinson AF, Schmieder RE, Schmid A, Choi JW, East C, Walton A, Hopper I, Cohen DL, Wilensky R, Lee DP, Ma A, Devireddy CM, Lea JP, Lurz PC, Fengler K, Davies J, Chapman N, Cohen SA, DeBruin V, Fahy M, Jones DE, Rothman M, Böhm M; SPYRAL HTN-OFF MED trial investigators*. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017 Nov 11;390(10108):2160-2170. doi: 10.1016/S0140-6736(17)32281-X. Epub 2017 Aug 28.
• Kandzari DE, Kario K, Mahfoud F, Cohen SA, Pilcher G, Pocock S, Townsend R, Weber MA, Böhm M. The SPYRAL HTN Global Clinical Trial Program: Rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. Am Heart J. 2016 Jan;171(1):82-91. doi: 10.1016/j.ahj.2015.08.021. Epub 2015 Sep 11. Review.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 31, 2020): 366
• Original Estimated Enrollment (submitted: May 6, 2015): 120
• Estimated Study Completion Date: March 2023
• Actual Primary Completion Date: April 30, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Individual has office systolic blood pressure (SBP) ≥ 150 mmHg and <180 mmHg and a diastolic blood pressure (DBP) ≥ 90 mmHg after being off medications.
• Individual has 24-hour Ambulatory Blood Pressure Monitoring (ABPM) average SBP ≥ 140 mmHg and < 170 mmHg.
• Individual is willing to discontinue current antihypertensive medications.

Exclusion Criteria:

• Individual lacks appropriate renal artery anatomy.
• Individual has estimated glomerular filtration rate (eGFR) of <45.
• Individual has type 1 diabetes mellitus or poorly-controlled type 2 diabetes mellitus.
• Individual has one or more episodes of orthostatic hypotension.
• Individual requires chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea.
• Individual has primary pulmonary hypertension.
• Individual is pregnant, nursing or planning to become pregnant.
• Individual has frequent intermittent or chronic pain that results in treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for two or more days per week over the month prior to enrollment.
• Individual has stable or unstable angina within 3 months of enrollment, myocardial infarction within 3 months of enrollment; heart failure, cerebrovascular accident or transient ischemic attack, or atrial fibrillation at any time.
• Individual works night shifts.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Canada, Germany, Greece, Ireland, Japan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02439749
• Other Study ID Numbers: SPYRAL HTN-OFF MED
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

• IPD Sharing Statement: Not Provided
• Responsible Party: Medtronic Vascular
• Study Sponsor: Medtronic Vascular
• Collaborators: Not Provided

Investigators

• Principal Investigator: Raymond Townsend, MD; University of Pennsylvania
• Principal Investigator: David Kandzari, MD; Piedmont Hospital
• Principal Investigator: Michael Böhm, MD; Universitätskliniken des Saarlandes
• Principal Investigator: Kazuomi Kario, MD; Jichi Medical University

• PRS Account: Medtronic Vascular
• Verification Date: October 2020