Improving the Results of Heart Bypass Surgery Using New Approaches to Surgery and Medication

NCT ID: NCT01047449

Last Updated: 2017-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2017-03-21

Brief Summary

Surgery for blocked arteries in the heart (coronary artery bypass grafting) can be accomplished using veins from the leg sewn onto the heart to provide an alternate path for blood flow, i.e. 'bypassing' the blockages. These veins themselves can block over time. This may result in part simply from the trauma from the surgery, in other words, by removing the vein from the leg and then sewing it to the heart. Another mechanism may be the abnormal metabolic processes within the body responsible for the plaque build-up of the heart arteries in the first place - this may lead to the blockages of the veins used for bypass. In the present era of heart bypass surgery, this incidence of veins blocking remains high despite advances in blood thinners and cholesterol medications. This study is designed to determine whether two new interventions may potentially reduce the incidence of blockages in the veins used for heart bypass surgery. One is a surgical technique significantly reducing the trauma associated with removing the leg vein prior to use as a bypass graft onto the heart. The second intervention is the use of a nutritional supplement before and after surgery which is composed of fish oils. The study will recruit sufficient patients to provide strong and relevant conclusions regarding both study questions. It will be highly applicable also because it will include approximately 1,550 patients from approximately 50 hospitals across many countries. We believe these techniques will result in significantly less vein blockages in patients one year after heart bypass surgery.

Detailed Description

Background: Saphenous vein grafts (SVG) remain the most widely used conduit for CABG. However, contemporary patency rates at one-year post CABG remain poor, despite optimal medical therapy. Recent trials (PREVENT IV) demonstrate that up to 45% of all patients have one or more SVG occluded at angiography one year post-CABG; up to 25% of all SVG are occluded at one year post-CABG angiography. Furthermore, patients with at least one SVG occluded had twice the incidence of perioperative MI, and thirteen times the composite endpoint of death, late MI or repeat revascularization at 12-18 months.

The proposed SUPERIOR SVG Trial is a prospective, international, multi-centre randomized controlled clinical trial (RCT). It utilizes a factorial design to elucidate the benefits of two interventions, one surgical and the other pharmacological, to improve saphenous vein graft patency after coronary artery bypass grafting surgery (CABG):

Surgical Arm: Does a novel atraumatic ("no touch") technique of pedicled saphenous vein graft (SVG) harvesting result in improved angiographic patency and clinical outcomes at 1 year, compared to conventional SVG harvesting techniques, in patients undergoing CABG.

Rationale: A Swedish cardiac surgical centre has published numerous studies demonstrating that harvesting the SVG with a cushion of surrounding fat and without vein graft distension, "no touch" technique, improved surrogate markers of vein preservation in operative specimens. Graft patency was superior in a single small RCT (8.5 year patency: "no touch" 90% vs. conventional 76%, p=0.01, adjusted OR 3.7, 95% CI 1.4-9.6, p=0.007).

Pharmacological Arm: Does N-3 polyunsaturated fatty acid (fish oil) oral supplementation result in improved angiographic patency and clinical outcomes at 1 year, compared to placebo, in patients undergoing CABG.

Rationale: In vivo studies showed levels of N-3 polyunsaturated fatty acids (PUFA; fish-oils) inversely correlate with the risk of coronary disease. Several large RCTs (more than 40,000 patients in aggregate) performed in diverse cardiovascular populations, have demonstrated moderate mortality benefits. A single RCT from the 90's found that that SVG patency was enhanced with fish oils.

Methods: Each patient will be randomized to a SVG harvested in the conventional fashion (open or endoscopic) or using the "no touch" technique (single-blinded). The pharmacological arm of the factorial design will have patients also randomized to fish-oil or placebo (double-blinded) starting prior to surgery and continuing for 1 year. The primary outcomes (Surgical Arm: proportion of study SVG grafts occluded; Pharmacological Arm: proportion of patients with ≥1 graft occluded) at 1 year CT angiography (window 9-15 months) will be compared between the treatment and control groups. Secondary endpoints include incidence of 50-99% study SVG stenosis at 1 year, adverse events and perioperative and 1 year clinical events (mortality, non-fatal MI, repeat revascularization).

A sample size of 615 patients/arm will provide adequate statistical power (Surgical Arm, Primary Outcome: study SVG graft occlusion, control event rate = 20%, no-touch event rate = 14%, RRR = 0.30, β = 0.2; Pharmacological Arm, Primary Outcome: patients with at least 1 graft occlusion, control event rate = 30%, fish oils event rate 22.5%, RRR = 0.25, β= 0.15). The total sample size has been increased 25% to 1550 patients as approximately 20% of recruited patients in angiographic trials fail to undergo follow-up angiography. Study patients will be enrolled over 39 months at 50 centers. Pilot funding has been secured from CIHR-CANNeCTIN to assess feasibility in 50 patients from 15 sites. A single interim analysis will be performed following completion of 50% of the CT angiograms, p<0.001.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

SVG harvest - conventional, placebo

Group Type: ACTIVE_COMPARATOR

No-touch SVG harvest vs conventional SVG harvest technique

Intervention Type: PROCEDURE

Saphenous vein harvested using the pedicled (no-touch) technique or using the conventional technique. Fish oil supplements/placebo (1g taken orally twice daily for 1 year post-op)

Fish oil supplementation vs placebo

Intervention Type: DIETARY_SUPPLEMENT

Fish oil supplementation \[1g tablets (55% fish oils - EPA:DHA 33%:22%)\] taken twice daily for 1 year post-op

SVG harvest - no-touch, fish oils

Group Type: EXPERIMENTAL

No-touch SVG harvest vs conventional SVG harvest technique

Intervention Type: PROCEDURE

Saphenous vein harvested using the pedicled (no-touch) technique or using the conventional technique. Fish oil supplements/placebo (1g taken orally twice daily for 1 year post-op)

Fish oil supplementation vs placebo

Intervention Type: DIETARY_SUPPLEMENT

Fish oil supplementation \[1g tablets (55% fish oils - EPA:DHA 33%:22%)\] taken twice daily for 1 year post-op

SVG harvest - no-touch, placebo

Group Type: PLACEBO_COMPARATOR

No-touch SVG harvest vs conventional SVG harvest technique

Intervention Type: PROCEDURE

Saphenous vein harvested using the pedicled (no-touch) technique or using the conventional technique. Fish oil supplements/placebo (1g taken orally twice daily for 1 year post-op)

Fish oil supplementation vs placebo

Intervention Type: DIETARY_SUPPLEMENT

Fish oil supplementation \[1g tablets (55% fish oils - EPA:DHA 33%:22%)\] taken twice daily for 1 year post-op

SVG harvest - conventional, fish oils

Group Type: ACTIVE_COMPARATOR

No-touch SVG harvest vs conventional SVG harvest technique

Intervention Type: PROCEDURE

Saphenous vein harvested using the pedicled (no-touch) technique or using the conventional technique. Fish oil supplements/placebo (1g taken orally twice daily for 1 year post-op)

Fish oil supplementation vs placebo

Intervention Type: DIETARY_SUPPLEMENT

Fish oil supplementation \[1g tablets (55% fish oils - EPA:DHA 33%:22%)\] taken twice daily for 1 year post-op

Interventions

No-touch SVG harvest vs conventional SVG harvest technique

Saphenous vein harvested using the pedicled (no-touch) technique or using the conventional technique. Fish oil supplements/placebo (1g taken orally twice daily for 1 year post-op)

Intervention Type: PROCEDURE

Fish oil supplementation vs placebo

Fish oil supplementation \[1g tablets (55% fish oils - EPA:DHA 33%:22%)\] taken twice daily for 1 year post-op

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Ocean Nutrition Omega Pure fish oil capsules

Eligibility Criteria

Inclusion Criteria

1. Age > 18 years

2. Able to provide informed consent

3. Isolated CABG, non-emergent, on- or off-pump (cardiopulmonary bypass)

4. Primary or re-do CABG (if re-do, all previous grafts must be occluded)

5. Left ventricular ejection fraction >20%

6. Require at least one SVG as part of revascularization strategy

7. Creatinine clearance of at least 30ml/min or higher

Exclusion Criteria

1. Unable to use greater SV due to previous vein stripping or poor quality on mandatory preoperative Duplex study and vein mapping

2. Contraindication to receiving follow-up 64-slice cardiac CT angiography (allergy to contrast dye, renal failure with a creatinine >180 µmol/L, uncontrolled atrial fibrillation precluding proper gating of study)

3. Pregnant women, or women of child-bearing age

4. Allergy to fish oil/fish products, and non-medicinal ingredients of the study product (corn oil,soybean oil,gelatin,glycerol, or carob colouring)

5. Already taking fish oil supplements regularly (daily use in past 30 days)

6. Congenital or acquired coagulation disorders

7. Patients considered to be of excessive risk of wound infection according to the clinical judgement of the site surgical investigator.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: collaborator

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Stephen E. Fremes

Head, Division of Cardiac & Vascular Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephen Fremes, MD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Locations

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Countries

Canada

References

Deb S, Singh SK, de Souza D, Chu MWA, Whitlock R, Meyer SR, Verma S, Jeppsson A, Al-Saleh A, Brady K, Rao-Melacini P, Belley-Cote EP, Tam DY, Devereaux PJ, Novick RJ, Fremes SE; SUPERIOR SVG Study Investigators. SUPERIOR SVG: no touch saphenous harvesting to improve patency following coronary bypass grafting (a multi-Centre randomized control trial, NCT01047449). J Cardiothorac Surg. 2019 May 2;14(1):85. doi: 10.1186/s13019-019-0887-x.

Reference Type: DERIVED

PMID: 31046806 (View on PubMed)

Other Identifiers

CANNeCTIN09-11

Identifier Type: -

Identifier Source: org_study_id