Effects of Remote Ischemic Preconditioning on Restenosis Post Lower Limb Revascularization Angioplasty

NCT02406131 | Suspended DMC

• 1 other identifier: C.A. 1238
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The investigators will established relation between restenosis and inflammatory response to shearing stress caused by angioplasty suggest that any mechanism that affect inflammatory response can consequently affect the restenosis rate. There is accumulated evidence that remote ischemic precondition has modifying suppressive effect on inflammatory response and the investigators hypothesized that RIPC may lead to reduction in post angioplasty restenosis rate.

Conditions

Peripheral Vascular Diseases

Keywords

Peripheral Vascular Diseases; Ischemic Preconditioning; Inflammation; Angioplasty; Restenosis; RCT

Outcome Measures

Primary Outcomes (2)

• Restenosis

  using Duplex scan 30% stenosis increase in time of flow up. Increase of less than or 50 % stenosis to 70% or more. Loss of 50% of gain in luminal diameter.

  6 months post procedure

• Changes in inflammatory and coagulation markers comparing the 2 groups

  CRP FBC D-Dimer Fibrinogen

  24 hours post procedure

Secondary Outcomes (5)

• Limb Amputation

  6 months post procedure

• Minor amputations

  6 months post procedure

• Percentage changes in ABI

  6 months post procedure

• Ulcer formation/ healing

  6 months post procedure

• Progression of Rutherford classification

  6 months post procedure

Other Outcomes (1)

• Related Data

  6 months post procedure

Study Arms (2)

Control Group:

NO INTERVENTION

This group will be getting all the routine work up including Duplex scan . we will add request for inflammatory and coagulation markers in their blood samples before and after intervention . The pre-op blood sample will be collected within the 24 hours before intervention and the post intervention in the 24 hrs after (second RIPC window). The repeated duplex scan will be schedule after 6 months.

RIPC Group

ACTIVE COMPARATOR

Remote Ischemic Preconditioning Group (RIPC):This group will have all the tests as for the control group with the additional component will be preconditioning. One hour prior to procedure candidates in this group will have structured intermittent periods of induced remote ischaemic preconditioning using standard blood pressure cuffs. The cuff will be inflated to 200 mmHg applied for 5 minutes alternating with 5 minutes rest to the total of 4 cycles, which needs 40 minutes.

Other: Remote Ischemic Preconditioning

Interventions

Remote Ischemic Preconditioning OTHER

standard blood pressure cuffs applied to upper limb . The cuff will be inflated to 200 mmHg applied for 5 minutes alternating with 5 minutes rest to the total of 4 cycles

RIPC Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patients planned for lower limb Angioplasty

You may not qualify if:

• Known upper limb PVD
• Previous history of upper limb deep vein thrombosis
• Patients on glibenclamide or nicorandil- May affect RIPC
• Raynaud's Disease
• Intra operative decision to use graft - will be documented

Sponsors & Collaborators

• National University of Ireland, Galway, Ireland: lead
• University College Hospital Galway: collaborator
• University Hospital of Limerick: collaborator

Study Sites (2)

University Collage Hospital Galway

Galway, Co Galway, Ireland

Location

Limerick University Hospital

Limerick, Ireland

Location

Related Publications (32)

• Friedman SG. Charles Dotter and the fiftieth anniversary of endovascular surgery. J Vasc Surg. 2015 Feb;61(2):556-8. doi: 10.1016/j.jvs.2014.09.012. Epub 2014 Oct 11. No abstract available.

  PMID: 25307132 BACKGROUND

• Berry D. The unlocking of the coronary arteries: origins of angioplasty. A short historical review of arterial dilatation from Dotter to the creative Gruentzig. Eur Heart J. 2009 Jun;30(12):1421-2. doi: 10.1093/eurheartj/ehp182. No abstract available.

  PMID: 19525552 BACKGROUND

• Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG; TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007 Jan;45 Suppl S:S5-67. doi: 10.1016/j.jvs.2006.12.037. No abstract available.

  PMID: 17223489 BACKGROUND

• Medical Advisory Secretariat. Stenting for peripheral artery disease of the lower extremities: an evidence-based analysis. Ont Health Technol Assess Ser. 2010;10(18):1-88. Epub 2010 Sep 1.

  PMID: 23074395 BACKGROUND

• Botev N. Population ageing in Central and Eastern Europe and its demographic and social context. Eur J Ageing. 2012 Feb 9;9(1):69-79. doi: 10.1007/s10433-012-0217-9. eCollection 2012 Mar.

  PMID: 28804408 BACKGROUND

• Anderson PL, Gelijns A, Moskowitz A, Arons R, Gupta L, Weinberg A, Faries PL, Nowygrod R, Kent KC. Understanding trends in inpatient surgical volume: vascular interventions, 1980-2000. J Vasc Surg. 2004 Jun;39(6):1200-8. doi: 10.1016/j.jvs.2004.02.039.

  PMID: 15192558 BACKGROUND

• Nowygrod R, Egorova N, Greco G, Anderson P, Gelijns A, Moskowitz A, McKinsey J, Morrissey N, Kent KC. Trends, complications, and mortality in peripheral vascular surgery. J Vasc Surg. 2006 Feb;43(2):205-16. doi: 10.1016/j.jvs.2005.11.002.

  PMID: 16476588 BACKGROUND

• Serruys PW, Luijten HE, Beatt KJ, Geuskens R, de Feyter PJ, van den Brand M, Reiber JH, ten Katen HJ, van Es GA, Hugenholtz PG. Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon. A quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months. Circulation. 1988 Feb;77(2):361-71. doi: 10.1161/01.cir.77.2.361.

  PMID: 2962786 BACKGROUND

• Schillinger M, Exner M, Mlekusch W, Haumer M, Rumpold H, Ahmadi R, Sabeti S, Wagner O, Minar E. Endovascular revascularization below the knee: 6-month results and predictive value of C-reactive protein level. Radiology. 2003 May;227(2):419-25. doi: 10.1148/radiol.2272020137. Epub 2003 Mar 20.

  PMID: 12649419 BACKGROUND

• Cejna M, Thurnher S, Illiasch H, Horvath W, Waldenberger P, Hornik K, Lammer J. PTA versus Palmaz stent placement in femoropopliteal artery obstructions: a multicenter prospective randomized study. J Vasc Interv Radiol. 2001 Jan;12(1):23-31. doi: 10.1016/s1051-0443(07)61397-9.

  PMID: 11200349 BACKGROUND

• Tsigkas GG, Karantalis V, Hahalis G, Alexopoulos D. Stent restenosis, pathophysiology and treatment options: a 2010 update. Hellenic J Cardiol. 2011 Mar-Apr;52(2):149-57. No abstract available.

  PMID: 21478125 BACKGROUND

• Schillinger M, Minar E. Restenosis after percutaneous angioplasty: the role of vascular inflammation. Vasc Health Risk Manag. 2005;1(1):73-8. doi: 10.2147/vhrm.1.1.73.58932.

  PMID: 17319099 BACKGROUND

• Kleinedler JJ, Foley JD, Orchard EA, Dugas TR. Novel nanocomposite stent coating releasing resveratrol and quercetin reduces neointimal hyperplasia and promotes re-endothelialization. J Control Release. 2012 Apr 10;159(1):27-33. doi: 10.1016/j.jconrel.2012.01.008. Epub 2012 Jan 17.

  PMID: 22269665 BACKGROUND

• Wahlgren CM, Sten-Linder M, Egberg N, Kalin B, Blohme L, Swedenborg J. The role of coagulation and inflammation after angioplasty in patients with peripheral arterial disease. Cardiovasc Intervent Radiol. 2006 Jul-Aug;29(4):530-5. doi: 10.1007/s00270-005-0159-0.

  PMID: 16729229 BACKGROUND

• Tschopl M, Tsakiris DA, Marbet GA, Labs KH, Jager K. Role of hemostatic risk factors for restenosis in peripheral arterial occlusive disease after transluminal angioplasty. Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3208-14. doi: 10.1161/01.atv.17.11.3208.

  PMID: 9409313 BACKGROUND

• Hausleiter J, Kastrati A, Mehilli J, Vogeser M, Zohlnhofer D, Schuhlen H, Goos C, Pache J, Dotzer F, Pogatsa-Murray G, Dirschinger J, Heemann U, Schomig A; OSIRIS Investigators. Randomized, double-blind, placebo-controlled trial of oral sirolimus for restenosis prevention in patients with in-stent restenosis: the Oral Sirolimus to Inhibit Recurrent In-stent Stenosis (OSIRIS) trial. Circulation. 2004 Aug 17;110(7):790-5. doi: 10.1161/01.CIR.0000138935.17503.35. Epub 2004 Aug 9.

  PMID: 15302787 BACKGROUND

• Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986 Nov;74(5):1124-36. doi: 10.1161/01.cir.74.5.1124.

  PMID: 3769170 BACKGROUND

• Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1993 Mar;87(3):893-9. doi: 10.1161/01.cir.87.3.893.

  PMID: 7680290 BACKGROUND

• Jensen HA, Loukogeorgakis S, Yannopoulos F, Rimpilainen E, Petzold A, Tuominen H, Lepola P, Macallister RJ, Deanfield JE, Makela T, Alestalo K, Kiviluoma K, Anttila V, Tsang V, Juvonen T. Remote ischemic preconditioning protects the brain against injury after hypothermic circulatory arrest. Circulation. 2011 Feb 22;123(7):714-21. doi: 10.1161/CIRCULATIONAHA.110.986497. Epub 2011 Feb 7.

  PMID: 21300953 BACKGROUND

• Wang Y, Shen J, Xiong X, Xu Y, Zhang H, Huang C, Tian Y, Jiao C, Wang X, Li X. Remote ischemic preconditioning protects against liver ischemia-reperfusion injury via heme oxygenase-1-induced autophagy. PLoS One. 2014 Jun 10;9(6):e98834. doi: 10.1371/journal.pone.0098834. eCollection 2014.

  PMID: 24914543 BACKGROUND

• Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008 Aug 1;79(3):377-86. doi: 10.1093/cvr/cvn114. Epub 2008 May 2.

  PMID: 18456674 BACKGROUND

• Souza Filho MV, Loiola RT, Rocha EL, Simao AF, Gomes AS, Souza MH, Ribeiro RA. Hind limb ischemic preconditioning induces an anti-inflammatory response by remote organs in rats. Braz J Med Biol Res. 2009 Oct;42(10):921-9. doi: 10.1590/s0100-879x2009005000025. Epub 2009 Sep 11.

  PMID: 19738981 BACKGROUND

• Zhang JQ, Wang Q, Xue FS, Li RP, Cheng Y, Cui XL, Liao X, Meng FM. Ischemic preconditioning produces more powerful anti-inflammatory and cardioprotective effects than limb remote ischemic postconditioning in rats with myocardial ischemia-reperfusion injury. Chin Med J (Engl). 2013 Oct;126(20):3949-55.

  PMID: 24157164 BACKGROUND

• Kim YH, Yoon DW, Kim JH, Lee JH, Lim CH. Effect of remote ischemic post-conditioning on systemic inflammatory response and survival rate in lipopolysaccharide-induced systemic inflammation model. J Inflamm (Lond). 2014 May 21;11:16. doi: 10.1186/1476-9255-11-16. eCollection 2014.

  PMID: 24904237 BACKGROUND

• He X, Zhao M, Bi XY, Yu XJ, Zang WJ. Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury in rats: role of ROS and eNOS. Lab Invest. 2013 Feb;93(2):168-80. doi: 10.1038/labinvest.2012.160. Epub 2012 Nov 12.

  PMID: 23147223 BACKGROUND

• Roviezzo F, Cuzzocrea S, Di Lorenzo A, Brancaleone V, Mazzon E, Di Paola R, Bucci M, Cirino G. Protective role of PI3-kinase-Akt-eNOS signalling pathway in intestinal injury associated with splanchnic artery occlusion shock. Br J Pharmacol. 2007 Jun;151(3):377-83. doi: 10.1038/sj.bjp.0707233. Epub 2007 Apr 23.

  PMID: 17450173 BACKGROUND

• Forstermann U, Munzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation. 2006 Apr 4;113(13):1708-14. doi: 10.1161/CIRCULATIONAHA.105.602532.

  PMID: 16585403 BACKGROUND

• Shimizu M, Saxena P, Konstantinov IE, Cherepanov V, Cheung MM, Wearden P, Zhangdong H, Schmidt M, Downey GP, Redington AN. Remote ischemic preconditioning decreases adhesion and selectively modifies functional responses of human neutrophils. J Surg Res. 2010 Jan;158(1):155-61. doi: 10.1016/j.jss.2008.08.010.

  PMID: 19540519 BACKGROUND

• Kharbanda RK, Peters M, Walton B, Kattenhorn M, Mullen M, Klein N, Vallance P, Deanfield J, MacAllister R. Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation. 2001 Mar 27;103(12):1624-30. doi: 10.1161/01.cir.103.12.1624.

  PMID: 11273988 BACKGROUND

• Konstantinov IE, Arab S, Kharbanda RK, Li J, Cheung MM, Cherepanov V, Downey GP, Liu PP, Cukerman E, Coles JG, Redington AN. The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol Genomics. 2004 Sep 16;19(1):143-50. doi: 10.1152/physiolgenomics.00046.2004. Epub 2004 Aug 10.

  PMID: 15304621 BACKGROUND

• Hausenloy DJ, Yellon DM. The second window of preconditioning (SWOP) where are we now? Cardiovasc Drugs Ther. 2010 Jun;24(3):235-54. doi: 10.1007/s10557-010-6237-9.

  PMID: 20496105 BACKGROUND

• Liang F, Liu S, Liu G, Liu H, Wang Q, Song B, Yao L. Remote ischaemic preconditioning versus no remote ischaemic preconditioning for vascular and endovascular surgical procedures. Cochrane Database Syst Rev. 2023 Jan 16;1(1):CD008472. doi: 10.1002/14651858.CD008472.pub3.

  PMID: 36645250 DERIVED

MeSH Terms

Conditions

Peripheral Vascular Diseases; Inflammation

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stewart Walsh, Professor

  NUIGalway - UCHG

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mr

Study Record Dates

• First Submitted: March 19, 2015
• First Posted: April 2, 2015
• Study Start: April 1, 2018
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: September 26, 2017

Record last verified: 2017-09

Locations

IE (2)