Renal Sympathetic Denervation for the Management of Chronic Hypertension

Uncontrolled Hypertension Clinical Trial

— RELIEF  

Official title:

Renal Sympathetic Denervation for the Management of Chronic Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01628172
• Other study ID #: GCO 11-0965
• Status: Completed
• Phase: N/A
• First received: June 12, 2012
• Last updated: June 28, 2016
• Start date: January 2011
• Est. completion date: March 2014

Study information

• Verified date: June 2016
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardCzech Republic: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Despite the development of numerous drug therapies designed to treat hypertension, it remains a considerable and poorly managed health, social and economic burden. For various reasons, including the significant health care costs of treatment, there are estimates that up to 65% of hypertensive patients have untreated and/or uncontrolled blood pressure (BP).

Aside from its impact on renal function, chronic hypertension significantly increases the risk for stroke, coronary artery disease, heart failure, and vascular disease. It is believed to be involved in the progression of cardiac arrhythmias. This link between hypertension and cardiovascular health has been well described; as has their combined effect on the aging and obesity-battling Western world.

The recently published results of the Symplicity HTN-2 trial (Renal sympathetic denervation in patients with treatment resistant hypertension) establishing the therapeutic benefit of catheter-based renal sympathetic denervation for hypertension, have enormous potential for the management of a large and challenging patient population. The proposed, multicenter trial will attempt to confirm and expand on this promising data by conducting a double-blinded, placebo-controlled trial.

Patients may qualify to participate in this research study if their doctor has determined that they have drug-resistant, chronic hypertension.

Overall participation in this research study should be about 13 months which includes about 1 month to start the study procedure and 12 months of follow-up after the study procedure.

Description:

Patients who qualify for the study and provide consent will undergo a renal angiogram in order to assess suitability for catheter-based renal sympathetic denervation. A renal angiogram is an x-ray study of the blood vessels in the kidney to evaluate for blockage, and abnormalities that could be affecting the blood supply to the kidney. It is performed by injecting contrast dye through a catheter (a tiny tube) into the blood vessels of the kidney. The study doctor will assess whether the renal arteries are suitable to receive catheter-based renal denervation.

Both groups will receive sedation or anesthesia prior to the beginning of the procedure.

The first group will undergo catheter-based sympathetic renal denervation. Renal Sympathetic Denervation is a procedure that uses a catheter probe inserted into the renal (kidney) artery that deactivates the nerves that are linked to high blood pressure.

The second group will only receive renal angiography without the delivery of ablative energy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• = 18 and = 85 years of age

• Uncontrolled hypertension (defined as SBP = 140 mmHg during 24Hr Ambulatory BP monitoring)

• Current treatment with = 3 anti-hypertensive drugs (including at least one diuretic)

• Accessibility of renal vasculature

• Ability to understand the requirements of the study

• Willingness to adhere to study restrictions and comply with all post-procedural follow-up requirements

Exclusion Criteria:

• Secondary cause of hypertension

• White coat hypertension

• Estimated GFR < 45

• Type 1 Diabetes

• Known renovascular abnormalities (eg, renal artery stenosis, previous renal artery stenting or angioplasty)

• Life expectancy <1 year for any medical condition

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Uncontrolled Hypertension

Intervention

Device:
• Biosense Webster Celcius Thermacool catheter
catheter-based sympathetic renal denervation

Locations

Country	Name	City	State
Czech Republic	Fakultní nemocnice u sv. Anny v Brne	Brno
Czech Republic	Na Homolce Hospital	Prague

Sponsors (2)

Lead Sponsor	Collaborator
Vivek Reddy	Biosense Webster, Inc.

Country where clinical trial is conducted

Czech Republic, 

References & Publications (26)

Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM; American Heart Association Professional Education Committee. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008 Jun 24;117(25):e510-26. doi: 10.1161/CIRCULATIONAHA.108.189141. — View Citation

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Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003 Dec;42(6):1206-52. Epub 2003 Dec 1. — View Citation

Cutler JA, Sorlie PD, Wolz M, Thom T, Fields LE, Roccella EJ. Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988-1994 and 1999-2004. Hypertension. 2008 Nov;52(5):818-27. doi: 10.1161/HYPERTENSIONAHA.108.113357. Epub 2008 Oct 13. — View Citation

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DiBona GF. Sympathetic nervous system and the kidney in hypertension. Curr Opin Nephrol Hypertens. 2002 Mar;11(2):197-200. Review. — View Citation

Esler M, Jennings G, Korner P, Willett I, Dudley F, Hasking G, Anderson W, Lambert G. Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension. 1988 Jan;11(1):3-20. Review. — View Citation

EVELYN KA, SINGH MM, CHAPMAN WP, PERERA GA, THALER H. Effect of thoracolumbar sympathectomy on the clinical course of primary (essential) hypertension. A ten-year study of 100 sympathectomized patients compared with individually matched, symptomatically treated control subjects. Am J Med. 1960 Feb;28:188-221. — View Citation

Fagius J. Sympathetic nerve activity in metabolic control--some basic concepts. Acta Physiol Scand. 2003 Mar;177(3):337-43. Review. — View Citation

Grassi G, Seravalle G, Quarti-Trevano F, Dell'Oro R, Bombelli M, Cuspidi C, Facchetti R, Bolla G, Mancia G. Adrenergic, metabolic, and reflex abnormalities in reverse and extreme dipper hypertensives. Hypertension. 2008 Nov;52(5):925-31. doi: 10.1161/HYPERTENSIONAHA.108.116368. Epub 2008 Sep 8. — View Citation

Hausberg M, Kosch M, Harmelink P, Barenbrock M, Hohage H, Kisters K, Dietl KH, Rahn KH. Sympathetic nerve activity in end-stage renal disease. Circulation. 2002 Oct 8;106(15):1974-9. — View Citation

Joles JA, Koomans HA. Causes and consequences of increased sympathetic activity in renal disease. Hypertension. 2004 Apr;43(4):699-706. Epub 2004 Feb 23. Review. — View Citation

Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan 15-21;365(9455):217-23. — View Citation

Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham WT, Esler M. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009 Apr 11;373(9671):1275-81. doi: 10.1016/S0140-6736(09)60566-3. Epub 2009 Mar 28. — View Citation

Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999 Mar 16;130(6):461-70. — View Citation

Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K, Ford E, Furie K, Go A, Greenlund K, Haase N, Hailpern S, Ho M, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott M, Meigs J, Mozaffarian D, Nichol G, O'Donnell C, Roger V, Rosamond W, Sacco R, Sorlie P, Stafford R, Steinberger J, Thom T, Wasserthiel-Smoller S, Wong N, Wylie-Rosett J, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009 Jan 27;119(3):e21-181. doi: 10.1161/CIRCULATIONAHA.108.191261. Epub 2008 Dec 15. Erratum in: Circulation. 2011 Oct 18;124(16):e424. Circulation. 2010 Jul 6;122(1):e11. Circulation. 2009 Jan 27;119(3):e182. — View Citation

Luippold G, Beilharz M, Mühlbauer B. Chronic renal denervation prevents glomerular hyperfiltration in diabetic rats. Nephrol Dial Transplant. 2004 Feb;19(2):342-7. — View Citation

MORRISSEY DM, BROOKES VS, COOKE WT. Sympathectomy in the treatment of hypertension; review of 122 cases. Lancet. 1953 Feb 28;1(6757):403-8. — View Citation

O'Brien E, Sheridan J, O'Malley K. Dippers and non-dippers. Lancet. 1988 Aug 13;2(8607):397. — View Citation

Sarafidis PA, Bakris GL. Resistant hypertension: an overview of evaluation and treatment. J Am Coll Cardiol. 2008 Nov 25;52(22):1749-57. doi: 10.1016/j.jacc.2008.08.036. Review. — View Citation

Schlaich MP, Lambert E, Kaye DM, Krozowski Z, Campbell DJ, Lambert G, Hastings J, Aggarwal A, Esler MD. Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and Angiotensin neuromodulation. Hypertension. 2004 Feb;43(2):169-75. Epub 2003 Nov 10. — View Citation

Schlaich MP, Socratous F, Hennebry S, Eikelis N, Lambert EA, Straznicky N, Esler MD, Lambert GW. Sympathetic activation in chronic renal failure. J Am Soc Nephrol. 2009 May;20(5):933-9. doi: 10.1681/ASN.2008040402. Epub 2008 Sep 17. Review. — View Citation

SMITHWICK RH, THOMPSON JE. Splanchnicectomy for essential hypertension; results in 1,266 cases. J Am Med Assoc. 1953 Aug 15;152(16):1501-4. — View Citation

Ye S, Zhong H, Yanamadala V, Campese VM. Renal injury caused by intrarenal injection of phenol increases afferent and efferent renal sympathetic nerve activity. Am J Hypertens. 2002 Aug;15(8):717-24. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in 24-hour ambulatory BP	Differences in 24-hour ambulatory blood pressure measurements recorded at baseline and at 6 months for each patient.	baseline and at 6 months	No
Secondary	change in office BP	Difference in office blood pressure measurements at 6 months and at 12 months as compared to baseline.	baseline, 6 months, and 12 months	No
Secondary	change in ambulatory BP	Difference in 24 hour ambulatory blood pressure measurements at 12 months compared to baseline	baseline and at 12 months	No
Secondary	Renal artery dimensions	Change in renal artery dimensions at 6 months.	baseline and at 6 months	No
Secondary	Creatinine	Differences in creatinine measurements recorded at baseline and at 6 months for each patient.	baseline and at 6 months	No