Skip to main content
Top
Published in: Trials 1/2013

Open Access 01-12-2013 | Study protocol

Renal sympathetic denervation versus antiarrhythmic drugs for drug-resistant hypertension and symptomatic atrial fibrillation (RSDforAF) trial: study protocol for a randomized controlled trial

Authors: Min Qiu, Yuehui Yin, Qijun Shan

Published in: Trials | Issue 1/2013

Login to get access

Abstract

Background

Recently, catheter-based renal sympathetic denervation (RSD) has been verified to be safely used to substantially reduce the levels of blood pressure, left ventricular hypertrophy, sleep apnea severity and norepinephrine spillover, and improve glucose tolerance. All these pathological changes are recognized as independent risk factors for the development and recurrence of atrial fibrillation (AF). A randomized, single-blind, parallel-control, multicenter clinical trial is being conducted to compare RSD with antiarrhythmic drugs (AAD) in patients with drug-resistant hypertension and symptomatic AF (RSDforAF trial).

Methods/design

Patients with drug-resistant hypertension and symptomatic AF will be randomized to RSD and the drug treatment groups. Patients will be followed for 12 months until study closure. Up to 200 patients may be enrolled in six medical centers in China. The primary objective is to study the effects of RSD on AF burden and blood pressure in patients with hypertension and symptomatic AF.

Discussion

RSDforAF trial will test the hypothesis that RSD is superior to AAD in reducing AF burden and blood pressure in patients with drug-resistant hypertension and symptomatic AF.

Trial registration

ClinicalTrials.gov, NCT01713270
Appendix
Available only for authorised users
Literature
1.
go back to reference Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Kay GN, Le Huezey JY, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann LS, Smith SJ, Priori SG, Estes NR, Ezekowitz MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM, Jacobs AK, Anderson JL, Albert N, Buller CE, Creager MA: ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011, 2011 (123): e269-e367.CrossRef Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Kay GN, Le Huezey JY, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann LS, Smith SJ, Priori SG, Estes NR, Ezekowitz MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM, Jacobs AK, Anderson JL, Albert N, Buller CE, Creager MA: ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011, 2011 (123): e269-e367.CrossRef
2.
go back to reference Healey JS, Connolly SJ: Atrial fibrillation: hypertension as a causative agent, risk factor for complications, and potential therapeutic target. Am J Cardiol. 2003, 91: 9G-14G.CrossRefPubMed Healey JS, Connolly SJ: Atrial fibrillation: hypertension as a causative agent, risk factor for complications, and potential therapeutic target. Am J Cardiol. 2003, 91: 9G-14G.CrossRefPubMed
3.
go back to reference 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, 373: 1275-1281. 10.1016/S0140-6736(09)60566-3.CrossRefPubMed 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, 373: 1275-1281. 10.1016/S0140-6736(09)60566-3.CrossRefPubMed
4.
go back to reference Witkowski A, Prejbisz A, Florczak E, Kadziela J, Sliwinski P, Bielen P, Michalowska I, Kabat M, Warchol E, Januszewicz M, Narkiewicz K, Somers VK, Sobotka PA, Januszewicz A: Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011, 58: 559-565. 10.1161/HYPERTENSIONAHA.111.173799.CrossRefPubMed Witkowski A, Prejbisz A, Florczak E, Kadziela J, Sliwinski P, Bielen P, Michalowska I, Kabat M, Warchol E, Januszewicz M, Narkiewicz K, Somers VK, Sobotka PA, Januszewicz A: Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011, 58: 559-565. 10.1161/HYPERTENSIONAHA.111.173799.CrossRefPubMed
5.
go back to reference Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M, Hoppe UC: Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012, 59: 901-909. 10.1016/j.jacc.2011.11.034.CrossRefPubMed Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M, Hoppe UC: Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012, 59: 901-909. 10.1016/j.jacc.2011.11.034.CrossRefPubMed
6.
go back to reference Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD: Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med. 2009, 361: 932-934. 10.1056/NEJMc0904179.CrossRefPubMed Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD: Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med. 2009, 361: 932-934. 10.1056/NEJMc0904179.CrossRefPubMed
7.
go back to reference Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ, Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, Kirchhof P, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE: 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Hear Rhythm. 2012, 9: 632-696. 10.1016/j.hrthm.2011.12.016.CrossRef Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ, Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, Kirchhof P, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE: 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Hear Rhythm. 2012, 9: 632-696. 10.1016/j.hrthm.2011.12.016.CrossRef
8.
go back to reference Ahmed H, Neuzil P, Skoda J, Petru J, Sediva L, Schejbalova M, Reddy VY: Renal sympathetic denervation using an irrigated radiofrequency ablation catheter for the management of drug-resistant hypertension. JACC Cardiovasc Interv. 2012, 5: 758-765.CrossRefPubMed Ahmed H, Neuzil P, Skoda J, Petru J, Sediva L, Schejbalova M, Reddy VY: Renal sympathetic denervation using an irrigated radiofrequency ablation catheter for the management of drug-resistant hypertension. JACC Cardiovasc Interv. 2012, 5: 758-765.CrossRefPubMed
9.
go back to reference Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, Shirokova N, Karaskov A, Mittal S, Steinberg JS: A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. J Am Coll Cardiol. 2012, 60: 1163-1170. 10.1016/j.jacc.2012.05.036.CrossRefPubMed Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, Shirokova N, Karaskov A, Mittal S, Steinberg JS: A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. J Am Coll Cardiol. 2012, 60: 1163-1170. 10.1016/j.jacc.2012.05.036.CrossRefPubMed
10.
go back to reference Sorgente A, Tung P, Wylie J, Josephson ME: Six year follow-up after catheter ablation of atrial fibrillation: a palliation more than a true cure. Am J Cardiol. 2012, 109: 1179-1186. 10.1016/j.amjcard.2011.11.058.CrossRefPubMed Sorgente A, Tung P, Wylie J, Josephson ME: Six year follow-up after catheter ablation of atrial fibrillation: a palliation more than a true cure. Am J Cardiol. 2012, 109: 1179-1186. 10.1016/j.amjcard.2011.11.058.CrossRefPubMed
11.
go back to reference Cosedis NJ, Johannessen A, Raatikainen P, Hindricks G, Walfridsson H, Kongstad O, Pehrson S, Englund A, Hartikainen J, Mortensen LS, Hansen PS: Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. N Engl J Med. 2012, 367: 1587-1595. 10.1056/NEJMoa1113566.CrossRef Cosedis NJ, Johannessen A, Raatikainen P, Hindricks G, Walfridsson H, Kongstad O, Pehrson S, Englund A, Hartikainen J, Mortensen LS, Hansen PS: Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. N Engl J Med. 2012, 367: 1587-1595. 10.1056/NEJMoa1113566.CrossRef
12.
go back to reference Kannel WB, Wolf PA, Benjamin EJ, Levy D: Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 1998, 82: 2N-9N. 10.1016/S0002-9149(98)00583-9.CrossRefPubMed Kannel WB, Wolf PA, Benjamin EJ, Levy D: Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 1998, 82: 2N-9N. 10.1016/S0002-9149(98)00583-9.CrossRefPubMed
13.
go back to reference Kalifa J, Jalife J, Zaitsev AV, Bagwe S, Warren M, Moreno J, Berenfeld O, Nattel S: Intra-atrial pressure increases rate and organization of waves emanating from the superior pulmonary veins during atrial fibrillation. Circulation. 2003, 108: 668-671. 10.1161/01.CIR.0000086979.39843.7B.CrossRefPubMed Kalifa J, Jalife J, Zaitsev AV, Bagwe S, Warren M, Moreno J, Berenfeld O, Nattel S: Intra-atrial pressure increases rate and organization of waves emanating from the superior pulmonary veins during atrial fibrillation. Circulation. 2003, 108: 668-671. 10.1161/01.CIR.0000086979.39843.7B.CrossRefPubMed
14.
go back to reference Burstein B, Nattel S: Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol. 2008, 51: 802-809. 10.1016/j.jacc.2007.09.064.CrossRefPubMed Burstein B, Nattel S: Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol. 2008, 51: 802-809. 10.1016/j.jacc.2007.09.064.CrossRefPubMed
15.
go back to reference Lau DH, Mackenzie L, Kelly DJ, Psaltis PJ, Brooks AG, Worthington M, Rajendram A, Kelly DR, Zhang Y, Kuklik P, Nelson AJ, Wong CX, Worthley SG, Rao M, Faull RJ, Edwards J, Saint DA, Sanders P: Hypertension and atrial fibrillation: evidence of progressive atrial remodeling with electrostructural correlate in a conscious chronically instrumented ovine model. Hear Rhythm. 2010, 7: 1282-1290. 10.1016/j.hrthm.2010.05.010.CrossRef Lau DH, Mackenzie L, Kelly DJ, Psaltis PJ, Brooks AG, Worthington M, Rajendram A, Kelly DR, Zhang Y, Kuklik P, Nelson AJ, Wong CX, Worthley SG, Rao M, Faull RJ, Edwards J, Saint DA, Sanders P: Hypertension and atrial fibrillation: evidence of progressive atrial remodeling with electrostructural correlate in a conscious chronically instrumented ovine model. Hear Rhythm. 2010, 7: 1282-1290. 10.1016/j.hrthm.2010.05.010.CrossRef
16.
go back to reference Patterson E, Lazzara R, Szabo B, Liu H, Tang D, Li YH, Scherlag BJ, Po SS: Sodium-calcium exchange initiated by the Ca2+ transient: an arrhythmia trigger within pulmonary veins. J Am Coll Cardiol. 2006, 47: 1196-1206. 10.1016/j.jacc.2005.12.023.CrossRefPubMed Patterson E, Lazzara R, Szabo B, Liu H, Tang D, Li YH, Scherlag BJ, Po SS: Sodium-calcium exchange initiated by the Ca2+ transient: an arrhythmia trigger within pulmonary veins. J Am Coll Cardiol. 2006, 47: 1196-1206. 10.1016/j.jacc.2005.12.023.CrossRefPubMed
17.
go back to reference Sharifov OF, Fedorov VV, Beloshapko GG, Glukhov AV, Yushmanova AV, Rosenshtraukh LV: Roles of adrenergic and cholinergic stimulation in spontaneous atrial fibrillation in dogs. J Am Coll Cardiol. 2004, 43: 483-490. 10.1016/j.jacc.2003.09.030.CrossRefPubMed Sharifov OF, Fedorov VV, Beloshapko GG, Glukhov AV, Yushmanova AV, Rosenshtraukh LV: Roles of adrenergic and cholinergic stimulation in spontaneous atrial fibrillation in dogs. J Am Coll Cardiol. 2004, 43: 483-490. 10.1016/j.jacc.2003.09.030.CrossRefPubMed
18.
go back to reference Oral H, Crawford T, Frederick M, Gadeela N, Wimmer A, Dey S, Sarrazin JF, Kuhne M, Chalfoun N, Wells D, Good E, Jongnarangsin K, Chugh A, Bogun F, Pelosi FJ, Morady F: Inducibility of paroxysmal atrial fibrillation by isoproterenol and its relation to the mode of onset of atrial fibrillation. J Cardiovasc Electrophysiol. 2008, 19: 466-470. 10.1111/j.1540-8167.2007.01089.x.CrossRefPubMed Oral H, Crawford T, Frederick M, Gadeela N, Wimmer A, Dey S, Sarrazin JF, Kuhne M, Chalfoun N, Wells D, Good E, Jongnarangsin K, Chugh A, Bogun F, Pelosi FJ, Morady F: Inducibility of paroxysmal atrial fibrillation by isoproterenol and its relation to the mode of onset of atrial fibrillation. J Cardiovasc Electrophysiol. 2008, 19: 466-470. 10.1111/j.1540-8167.2007.01089.x.CrossRefPubMed
19.
go back to reference Kuhlkamp V, Schirdewan A, Stangl K, Homberg M, Ploch M, Beck OA: Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. 2000, 36: 139-146. 10.1016/S0735-1097(00)00693-8.CrossRefPubMed Kuhlkamp V, Schirdewan A, Stangl K, Homberg M, Ploch M, Beck OA: Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. 2000, 36: 139-146. 10.1016/S0735-1097(00)00693-8.CrossRefPubMed
20.
go back to reference Nergardh AK, Rosenqvist M, Nordlander R, Frick M: Maintenance of sinus rhythm with metoprolol CR initiated before cardioversion and repeated cardioversion of atrial fibrillation: a randomized double-blind placebo-controlled study. Eur Heart J. 2007, 28: 1351-1357. 10.1093/eurheartj/ehl544.CrossRefPubMed Nergardh AK, Rosenqvist M, Nordlander R, Frick M: Maintenance of sinus rhythm with metoprolol CR initiated before cardioversion and repeated cardioversion of atrial fibrillation: a randomized double-blind placebo-controlled study. Eur Heart J. 2007, 28: 1351-1357. 10.1093/eurheartj/ehl544.CrossRefPubMed
21.
go back to reference Chang CM, Wu TJ, Zhou S, Doshi RN, Lee MH, Ohara T, Fishbein MC, Karagueuzian HS, Chen PS, Chen LS: Nerve sprouting and sympathetic hyperinnervation in a canine model of atrial fibrillation produced by prolonged right atrial pacing. Circulation. 2001, 103: 22-25. 10.1161/01.CIR.103.1.22.CrossRefPubMed Chang CM, Wu TJ, Zhou S, Doshi RN, Lee MH, Ohara T, Fishbein MC, Karagueuzian HS, Chen PS, Chen LS: Nerve sprouting and sympathetic hyperinnervation in a canine model of atrial fibrillation produced by prolonged right atrial pacing. Circulation. 2001, 103: 22-25. 10.1161/01.CIR.103.1.22.CrossRefPubMed
22.
go back to reference Yi Z, Zhang HC, Zhang P, Liu G, Lu P, Sun JL, Liu B, Guo JH: The relationship of paroxysmal atrial fibrillation and regional sympathetic innervations in the atria and pulmonary veins: experiment with dogs. Zhonghua Yi Xue Za Zhi. 2007, 87: 3433-3435.PubMed Yi Z, Zhang HC, Zhang P, Liu G, Lu P, Sun JL, Liu B, Guo JH: The relationship of paroxysmal atrial fibrillation and regional sympathetic innervations in the atria and pulmonary veins: experiment with dogs. Zhonghua Yi Xue Za Zhi. 2007, 87: 3433-3435.PubMed
23.
go back to reference Shen MJ, Choi EK, Tan AY, Lin SF, Fishbein MC, Chen LS, Chen PS: Neural mechanisms of atrial arrhythmias. Nat Rev Cardiol. 2012, 9: 30-39. 10.1038/nchembio.1114.CrossRef Shen MJ, Choi EK, Tan AY, Lin SF, Fishbein MC, Chen LS, Chen PS: Neural mechanisms of atrial arrhythmias. Nat Rev Cardiol. 2012, 9: 30-39. 10.1038/nchembio.1114.CrossRef
24.
go back to reference Zhao Q, Yu S, Zou M, Dai Z, Wang X, Xiao J, Huang C: Effect of renal sympathetic denervation on the inducibility of atrial fibrillation during rapid atrial pacing. J Interv Card Electrophysiol. 2012, 35: 119-125. 10.1007/s10840-012-9717-y.CrossRefPubMed Zhao Q, Yu S, Zou M, Dai Z, Wang X, Xiao J, Huang C: Effect of renal sympathetic denervation on the inducibility of atrial fibrillation during rapid atrial pacing. J Interv Card Electrophysiol. 2012, 35: 119-125. 10.1007/s10840-012-9717-y.CrossRefPubMed
25.
go back to reference Linz D, Mahfoud F, Schotten U, Ukena C, Neuberger HR, Wirth K, Bohm M: Renal sympathetic denervation suppresses postapneic blood pressure rises and atrial fibrillation in a model for sleep apnea. Hypertension. 2012, 60: 172-178. 10.1161/HYPERTENSIONAHA.112.191965.CrossRefPubMed Linz D, Mahfoud F, Schotten U, Ukena C, Neuberger HR, Wirth K, Bohm M: Renal sympathetic denervation suppresses postapneic blood pressure rises and atrial fibrillation in a model for sleep apnea. Hypertension. 2012, 60: 172-178. 10.1161/HYPERTENSIONAHA.112.191965.CrossRefPubMed
26.
go back to reference Linz D, Mahfoud F, Schotten U, Ukena C, Hohl M, Neuberger HR, Wirth K, Bohm M: Renal sympathetic denervation provides ventricular rate control but does not prevent atrial electrical remodeling during atrial fibrillation. Hypertension. 2013, 61 (1): 225-231. 10.1161/HYPERTENSIONAHA.111.00182.CrossRefPubMed Linz D, Mahfoud F, Schotten U, Ukena C, Hohl M, Neuberger HR, Wirth K, Bohm M: Renal sympathetic denervation provides ventricular rate control but does not prevent atrial electrical remodeling during atrial fibrillation. Hypertension. 2013, 61 (1): 225-231. 10.1161/HYPERTENSIONAHA.111.00182.CrossRefPubMed
27.
go back to reference Vollmann D, Sossalla S, Schroeter MR, Zabel M: Renal artery ablation instead of pulmonary vein ablation in a hypertensive patient with symptomatic, drug-resistant, persistent atrial fibrillation. Clin Res Cardiol. 2012, 102 (4): 315-318.CrossRefPubMedPubMedCentral Vollmann D, Sossalla S, Schroeter MR, Zabel M: Renal artery ablation instead of pulmonary vein ablation in a hypertensive patient with symptomatic, drug-resistant, persistent atrial fibrillation. Clin Res Cardiol. 2012, 102 (4): 315-318.CrossRefPubMedPubMedCentral
Metadata
Title
Renal sympathetic denervation versus antiarrhythmic drugs for drug-resistant hypertension and symptomatic atrial fibrillation (RSDforAF) trial: study protocol for a randomized controlled trial
Authors
Min Qiu
Yuehui Yin
Qijun Shan
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Trials / Issue 1/2013
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-14-168

Other articles of this Issue 1/2013

Trials 1/2013 Go to the issue