Randomized Endo-Vein Graft Prospective (REGROUP)

CSP #588 - Randomized Endo-Vein Graft Prospective (REGROUP) Trial

Coronary artery bypass grafting (CABG) is the most common major surgical procedure in the United States with over 300,000 cases performed each year. To restore blood flow to the heart, vascular conduits from another part of the body are procured to create a bypass around critically blocked coronary arteries. The left internal thoracic artery is the conduit of choice for CABG due to its superior long-term patency. However, almost all patients referred for CABG require additional grafts to provide complete revascularization. This necessitates the harvest of other vessels, most commonly the saphenous vein which is used almost ubiquitously in contemporary CABG with an average of two vein grafts per CABG procedure. In the last 10 years, Endoscopic Vein Harvesting (EVH) has been recommended as the preferred method over the traditional open harvesting technique (OVH) because it provides a minimally invasive approach. However, more recent investigations indicate potential for reduced long-term bypass graft patency and worse clinical outcomes with EVH. The long term impact of EVH on clinical outcomes has never been investigated on a large scale using a definitive, adequately powered, prospective Randomized Controlled Trial (RCT) with long-term follow-up.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Bypass Grafting
• Intervention / Treatment: Procedure: Vein Harvesting Procedures

Detailed Description

CSP #588 - REGROUP is a randomized, intent-to-treat, two-arm, parallel design, multicenter study. Cardiac Surgery Programs at Veterans Affairs Medical Centers (VAMC) with expertise in performing both EVH and OVH will be invited to participate in the study. Subjects requiring elective or urgent CABG using cardiopulmonary bypass with use of at least one SVG will be screened for enrollment using established inclusion/exclusion criteria. Enrolled Subjects will be randomized to one of the two arms (EVH or OVH) after an experienced vein harvester is identified and assigned. Intraoperative assessments will be collected and post-operative assessments will be completed 24 hours post-surgery. Additional assessments will be completed at the time of discharge or at the 30-day post-surgery date if the subject is still in the hospital. Assessment of leg wound complications will be completed at the time of discharge and at six-week post-surgery. Telephone follow-ups will occur at three-month interval post-surgery until the participating sites are decommissioned at the end of the trial period (which would be approximately 4.5 years after the site initiations). For long-term MACE outcomes, passive follow up for MACE events using VA databases (CPRS, VASQIP) will be performed centrally by the Study Chair's office for another 2 years.

• Study Type: Interventional
• Enrollment (Actual): 1150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85723
      • Southern Arizona VA Health Care System, Tucson, AZ
  • California
    • San Francisco, California, United States, 94121
      • San Francisco VA Medical Center, San Francisco, CA
  • Florida
    • Gainesville, Florida, United States, 32608
      • North Florida/South Georgia Veterans Health System, Gainesville, FL
    • Miami, Florida, United States, 33125
      • Miami VA Healthcare System, Miami, FL
    • Tampa, Florida, United States, 33612
      • James A. Haley Veterans' Hospital, Tampa, FL
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
      • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Health Care System, Minneapolis, MN
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108-5153
      • New Mexico VA Health Care System, Albuquerque, NM
  • New York
    • New York, New York, United States, 10010
      • Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
  • North Carolina
    • Asheville, North Carolina, United States, 28805
      • Asheville VA Medical Center, Asheville, NC
    • Durham, North Carolina, United States, 27705
      • Durham VA Medical Center, Durham, NC
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Louis Stokes VA Medical Center, Cleveland, OH
  • Oregon
    • Portland, Oregon, United States, 97239
      • VA Portland Health Care System, Portland, OR
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15240
      • VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
  • Texas
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center, Houston, TX
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53295-1000
      • Clement J. Zablocki VA Medical Center, Milwaukee, WI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age years 18 years or older
• Elective or Urgent CABG-only
• Median sternotomy approach
• At least one coronary bypass planned using saphenous vein graft for conduit
• Experienced EVH/OVH harvester available for procedure

Exclusion Criteria:

• Combined valve procedure planned
• Moderate or severe valve disease (see definition of moderate/severe valve)
• Hemodynamically unstable or in cardiogenic shock
• Enrolled in another therapeutic or interventional study
• Off-pump CABG procedure planned
• Limited life expectancy < 1 year
• History of lower extremities venous stripping or ligation
• Inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Endoscopic Vein Harvest (EVH); An endoscopic vein harvest allows a portion of vein from the inside of the leg to be removed through small incisions. This reduces the length of the incision by several inches. An endoscope, or video camera, is used to view the vein and remove the needed length.	Procedure: Vein Harvesting Procedures; Open Vein Harvesting is the traditional method of saphenectomy for CABG. It is performed under direct vision using a single long incision or, more commonly, multiple smaller incisions (referred to as "bridging" technique) along the course of the vein. This approach minimizes manipulation and direct trauma to the conduit but is associated with potential for discomfort and leg wound healing complications. Endoscopic Vein Harvesting is a minimally invasive procedure that was developed to eliminate the need for long incisions associated with OVH. EVH reduces the risk of wound infections and other leg wound complications but may be more traumatic to the conduit than OVH.
Other: Open Vein Harvest (OVH); Open vein harvesting is the traditional method for vein harvesting. It is performed under direct vision using a single long incision or, more commonly, multiple-smaller incisions (referred to as "bridging" technique) along the course of the vein.	Procedure: Vein Harvesting Procedures; Open Vein Harvesting is the traditional method of saphenectomy for CABG. It is performed under direct vision using a single long incision or, more commonly, multiple smaller incisions (referred to as "bridging" technique) along the course of the vein. This approach minimizes manipulation and direct trauma to the conduit but is associated with potential for discomfort and leg wound healing complications. Endoscopic Vein Harvesting is a minimally invasive procedure that was developed to eliminate the need for long incisions associated with OVH. EVH reduces the risk of wound infections and other leg wound complications but may be more traumatic to the conduit than OVH.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of First MACE During Active Follow-up Period.	Incidence of first MACE estimated via Kaplan Meier survival analysis (MACE defined as death from any cause, repeat revascularization, myocardial infarction) during the active follow-up period.	Varying timeframe for each participant with a minimum of 1 year and a maximum 4.5 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACE at One Year.	Proportion of patients with MACE (death from any cause, repeat revascularization, myocardial infarction) at one year postoperatively.	1 year
MACE at Three Years.	Proportion of patients with MACE (death from any cause, repeat revascularization, myocardial infarction) at three years postoperatively.	3 years
Incidence of First MACE Over the Entire Follow-up Period (Active and Passive).	Incidence of first MACE estimated via Kaplan Meier survival analysis (MACE defined as death from any cause, repeat revascularization, myocardial infarction) during the entire follow-up period (active and passive).	Varying timeframe for each participant with a minimum of 3 years and a maximum of 6.5 years

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Study Chair: Marco A Zenati, MD MSc, VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Publications and helpful links

General Publications

• Zenati MA, Gaziano JM, Collins JF, Biswas K, Gabany JM, Quin JA, Bitondo JM, Bakaeen FG, Kelly RF, Shroyer AL, Bhatt DL. Choice of vein-harvest technique for coronary artery bypass grafting: rationale and design of the REGROUP trial. Clin Cardiol. 2014 Jun;37(6):325-30. doi: 10.1002/clc.22267. Epub 2014 Mar 14.
• Wagner TH, Hattler B, Stock EM, Biswas K, Bhatt DL, Bakaeen FG, Gujral K, Zenati MA. Costs of Endoscopic vs Open Vein Harvesting for Coronary Artery Bypass Grafting: A Secondary Analysis of the REGROUP Trial. JAMA Netw Open. 2022 Jun 1;5(6):e2217686. doi: 10.1001/jamanetworkopen.2022.17686.
• Shapeton AD, Leissner KB, Zorca SM, Amirfarzan H, Stock EM, Biswas K, Haime M, Srinivasa V, Quin JA, Zenati MA. Epiaortic Ultrasound for Assessment of Intraluminal Atheroma; Insights from the REGROUP Trial. J Cardiothorac Vasc Anesth. 2020 Mar;34(3):726-732. doi: 10.1053/j.jvca.2019.10.053. Epub 2019 Nov 9.
• Zenati MA, Bhatt DL, Bakaeen FG, Stock EM, Biswas K, Gaziano JM, Kelly RF, Tseng EE, Bitondo J, Quin JA, Almassi GH, Haime M, Hattler B, DeMatt E, Scrymgeour A, Huang GD; REGROUP Trial Investigators. Randomized Trial of Endoscopic or Open Vein-Graft Harvesting for Coronary-Artery Bypass. N Engl J Med. 2019 Jan 10;380(2):132-141. doi: 10.1056/NEJMoa1812390. Epub 2018 Nov 11.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2013
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): October 30, 2020

Study Registration Dates

• First Submitted: April 18, 2013
• First Submitted That Met QC Criteria: May 6, 2013
• First Posted (Estimate): May 9, 2013

Study Record Updates

• Last Update Posted (Actual): December 15, 2021
• Last Update Submitted That Met QC Criteria: November 19, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Coronary artery disease; CABG; Graft failure; Saphenous vein graft; Coronary revascularization; Endoscopic vein harvest
• Other Study ID Numbers: 588

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No