Clinical trial NCT03501303: A Clinical Trial on No-touch Vein Graft (NT-graft) in Coronary Surgery
Official title: A Nordic, Multicentre, Prospective, Randomized, Register Based, Clinical Trial on No-touch Vein Graft (NT-graft) in Coronary Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemic Heart Disease
Lead sponsor: Uppsala University
Sponsor class: OTHER
First posted: 2018-04-18
Enrollment: 902
Sex: ALL
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In an online randomization module the randomization will be performed with permuted block randomization to 1:1 ratio.
Primary purpose: TREATMENT

Brief summary: The primary objective in this study is to investigate if vein grafts harvested and implanted with the non-touch technique are superior to conventional vein graft technique with respect to mid-term patency, in patients undergoing CABG surgery.

Detailed description: Coronary artery bypass grafting (CABG) is the most common surgical procedure aimed against ischemic heart disease (IHD) in Sweden. Early and late success of CABG is the result of sustained patency of the bypass grafts. The choice of conduit (graft) for CABG has been shown to impact graft patency. The excellent early and late patency of in situ left internal thoracic artery (LITA) has stimulated the use of other arterial grafts, such as the radial artery (RA) and the right internal thoracic artery (RITA). However, target coronary vessels/lesions are limitations for the use of RITA and RA, and concerns regarding postoperative sternal wound infection with increases of early morbidity and mortality are reasons for limited use of bilateral ITA. The saphenous vein grafts (SVG), together with the left internal thoracic artery, are still the most commonly used conduits in CABG surgery.

Vein graft failure is associated with recurrence of angina and one of the primary reasons for reintervention, either by redo CABG or percutaneous coronary intervention (PCI). Early vein graft failure is not uncommon, and it was shown in the PREVENT IV multi-center trial6, that vein graft failure (occluded or stenosed) had occurred in 27% of all vein grafts at one year.

Despite this, SVG remains as an important conduit for most patients in contemporary bypass surgery and every effort should focus on promoting short and long-term patency of SVG. Previous studies by Souza have demonstrated that harvesting the SVG with a pedicle of surrounding tissue and without vein graft distension, the so-called "No touch" technique (NT), significantly improve patency compared with conventional technique i.e. stripping the vein of all adventitial tissue and distension prior to implantation. An international multi center randomized controlled clinical trial, (SUPERIOR SVG, NCT01047449) including 12 centers and 250 patients, was recently presented and showed favorable but not significant results for No touch vein grafts compared to conventional vein grafts. The protocol did not include cardiac computed tomography angiography (CCTA) for every patient which is an important difference compared to our planned study.

The major limitation regarding the putative benefit of NT technique of vein harvesting is that most of the data has all been derived from a single center. The surgical vein graft harvesting technique for NT grafts is more demanding. Therefore, there is a clear clinical equipoise to perform a multi-center randomized clinical trial to validate the excellent single-center results and determine whether the NT technique is reproducible, feasible and generalizable.

Eligibility criteria: Inclusion Criteria:

* first time CABG patients
* age up to 80 years at the time for inclusion
* need for at least one vein graft
* able to provide informed consent and accepted for isolated primary non-emergent CABG.

Exclusion Criteria:

* unable to use greater saphenous vein grafts (SVG) due to previous vein stripping or poor vein quality
* allergy to contrast dye
* renal failure with glomerular filtration rate (GFR)\<15 ml/min
* coagulation disorders
* excessive risk of wound infection
* participation in other interventional trial on grafts
* any condition that seriously increases the risk of non-compliance or loss of follow-up

Primary outcomes:
measure: Saphenous vein grafts (SVGs) occluded/stenosed
timeFrame: Follow up period is from inclusion and surgery up to two years after.
Secondary outcomes:
measure: Major adverse cardiac events (MACE) 1
timeFrame: Follow up period is from inclusion and surgery up to two years after.
measure: MACE 2
timeFrame: Follow up period is from inclusion and surgery up to two years after.
measure: MACE 3
timeFrame: Follow up period is from inclusion and surgery up to two years after.
measure: Wound complications
timeFrame: Follow up period is from inclusion and surgery up to two years after.
measure: Vein-graft stenosis
timeFrame: Follow up period is from inclusion and surgery up to two years after.
Other outcomes:
measure: Questions about wound healing
timeFrame: At 3 months and 2 years after CABG surgery.
measure: Questions about Quality of Life
timeFrame: At 2 years after CABG surgery.
Locations:
city: Aarhus
country: Denmark
facility: Aarhus
city: Göteborg
country: Sweden
facility: Göteborg
city: Karlskrona
country: Sweden
facility: Karlskrona
city: Linköping
country: Sweden
facility: Linköping
city: Lund
country: Sweden
facility: Lund
city: Stockholm
country: Sweden
facility: Karolinska Sjukhuset
city: Umeå
country: Sweden
facility: Umeå
city: Uppsala
country: Sweden
facility: Uppsala
city: Örebro
country: Sweden
facility: Örebro, Sweden
Study officials:
affiliation: Uppsala University Hospital
name: Stefan Thelin, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Loop FD, Lytle BW, Cosgrove DM, Stewart RW, Goormastic M, Williams GW, Golding LA, Gill CC, Taylor PC, Sheldon WC, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med. 1986 Jan 2;314(1):1-6. doi: 10.1056/NEJM198601023140101.
citation: Desai ND, Cohen EA, Naylor CD, Fremes SE; Radial Artery Patency Study Investigators. A randomized comparison of radial-artery and saphenous-vein coronary bypass grafts. N Engl J Med. 2004 Nov 25;351(22):2302-9. doi: 10.1056/NEJMoa040982.
citation: Lytle BW, Blackstone EH, Loop FD, Houghtaling PL, Arnold JH, Akhrass R, McCarthy PM, Cosgrove DM. Two internal thoracic artery grafts are better than one. J Thorac Cardiovasc Surg. 1999 May;117(5):855-72. doi: 10.1016/S0022-5223(99)70365-X.
citation: Parisian Mediastinitis Study Group. Risk factors for deep sternal wound infection after sternotomy: a prospective, multicenter study. J Thorac Cardiovasc Surg. 1996 Jun;111(6):1200-7. doi: 10.1016/s0022-5223(96)70222-2.
citation: Guru V, Fremes SE, Tu JV. How many arterial grafts are enough? A population-based study of midterm outcomes. J Thorac Cardiovasc Surg. 2006 May;131(5):1021-8. doi: 10.1016/j.jtcvs.2005.09.036. Epub 2006 Apr 25.
citation: Alexander JH, Hafley G, Harrington RA, Peterson ED, Ferguson TB Jr, Lorenz TJ, Goyal A, Gibson M, Mack MJ, Gennevois D, Califf RM, Kouchoukos NT; PREVENT IV Investigators. Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: a randomized controlled trial. JAMA. 2005 Nov 16;294(19):2446-54. doi: 10.1001/jama.294.19.2446.
citation: Souza DS, Dashwood MR, Tsui JC, Filbey D, Bodin L, Johansson B, Borowiec J. Improved patency in vein grafts harvested with surrounding tissue: results of a randomized study using three harvesting techniques. Ann Thorac Surg. 2002 Apr;73(4):1189-95. doi: 10.1016/s0003-4975(02)03425-2.
citation: Souza DS, Johansson B, Bojo L, Karlsson R, Geijer H, Filbey D, Bodin L, Arbeus M, Dashwood MR. Harvesting the saphenous vein with surrounding tissue for CABG provides long-term graft patency comparable to the left internal thoracic artery: results of a randomized longitudinal trial. J Thorac Cardiovasc Surg. 2006 Aug;132(2):373-8. doi: 10.1016/j.jtcvs.2006.04.002.
citation: Dashwood MR, Savage K, Dooley A, Shi-Wen X, Abraham DJ, Souza DS. Effect of vein graft harvesting on endothelial nitric oxide synthase and nitric oxide production. Ann Thorac Surg. 2005 Sep;80(3):939-44. doi: 10.1016/j.athoracsur.2005.03.042.
citation: Dashwood MR, Savage K, Tsui JC, Dooley A, Shaw SG, Fernandez Alfonso MS, Bodin L, Souza DS. Retaining perivascular tissue of human saphenous vein grafts protects against surgical and distension-induced damage and preserves endothelial nitric oxide synthase and nitric oxide synthase activity. J Thorac Cardiovasc Surg. 2009 Aug;138(2):334-40. doi: 10.1016/j.jtcvs.2008.11.060. Epub 2009 Mar 10.
citation: Samano N, Geijer H, Liden M, Fremes S, Bodin L, Souza D. The no-touch saphenous vein for coronary artery bypass grafting maintains a patency, after 16 years, comparable to the left internal thoracic artery: A randomized trial. J Thorac Cardiovasc Surg. 2015 Oct;150(4):880-8. doi: 10.1016/j.jtcvs.2015.07.027. Epub 2015 Jul 15.
citation: Ragnarsson S, Janiec M, Modrau IS, Dreifaldt M, Ericsson A, Holmgren A, Hultkvist H, Jeppsson A, Sartipy U, Ternstrom L, Per Vikholm MD, de Souza D, James S, Thelin S. No-touch saphenous vein grafts in coronary artery surgery (SWEDEGRAFT): Rationale and design of a multicenter, prospective, registry-based randomized clinical trial. Am Heart J. 2020 Jun;224:17-24. doi: 10.1016/j.ahj.2020.03.009. Epub 2020 Mar 13.