METHODS

Trial Design

A single-centre, parallel group, factorial RCT with blinding of participants and clinical and research staff not involved in the operation. Participants were randomly allocated in a 1:1:1:1 ratio to one of four treatment groups; conventional harvest and high-pressure test, conventional harvest, and low-pressure test, pedicled harvest and high-pressure test, or pedicled harvest and low-pressure test.
The study was approved by a National Health Service Research Ethics Committee (Wiltshire ref. 09/H0104/28). The trial was registered as ISRCTN10567790. Patients and the public did not contribute to the design or conduct of the trial.

Participants

Adults aged 18 and over undergoing first time non-emergency CABG (either on or off-pump) at the Bristol Heart Institute, with at least one saphenous vein graft and not requiring valve replacement/repair or an aortic procedure were eligible to take part.[18, 19] Patients with congestive heart failure, ejection fraction <30%, pre-operative serum creatinine >104μmol/L, peripheral vascular disease, allergy to iodinated contrast media, participating in another interventional study, or unwilling to participate in follow-up were excluded. All participants provided written informed consent.

Interventions

Harvest technique : vein grafts were harvested either with(pedicle harvest) or without (conventional harvest) the pedicle of surrounding fat and adventitia, as described by Souza.[11] All grafts were harvested using a no-touch technique and were left in-situ until systemic heparinisation.
Pressure test for leaks : vein grafts, excised following systemic heparinisation, were either flushed with heparinised blood from a syringe (conventional high pressure test) or attached to a side arm of the aortic canulae in patients undergoing on-pump surgery, or anastomosed first to the ascending aorta in off-pump surgery, and flushed with blood at systemic pressure (low pressure test).[8]

Outcomes

The protocol-defined primary outcomes were vein graft disease as measured by i) wall thickness and ii) lumen diameter assessed using IVUS at 12 months post-surgery. Multiple IVUS measurements were taken per graft and the patient-level mean for each measurement was used. Wall thickness at baseline was measured by histological analysis of a short segment of the harvested vein from the end of each graft retrieved prior to completion of the proximal anastomoses.
Secondary outcomes were lumen diameter and graft patency assessed by quantitative angiography at 12 months; serious adverse events (SAEs); wound infection using the ASEPSIS scoring system; duration of postoperative stay; leg wound pain or dysaesthesia at 3 and 12 months assessed using the neuropathic pain symptom inventory (NPSI) scoring system; and readmissions to hospital within 12 months.[20, 21] SAEs not listed in the study protocol were coded using the Medical Dictionary for Regulatory Activities (version 19.0;McLean, Va).

Sample Size

The sample size was set at 96 patients (24 per group), which is sufficient to detect an effect size of 0.5 standard deviations (SD) with 80% power and 5% statistical significance, assuming no interaction between the method of harvesting the graft and the method of testing for leaks, a correlation of 0.7 between the one pre- and one post-randomisation measurement and allowing for 25% loss to follow-up.
An effect size of 0.5 SD equates to differences of ≈1.2mm in the mean graft wall thickness and ≈2.4mm2 in lumen area between pedicled and conventional harvest groups, or between high- and low-pressure test groups, assuming estimated within-group SDs of 2.33 and 4.69 respectively.[16] The sample size calculation assumes only one graft per patient whereas, in practice, some patients received two or more vein grafts.[18] Therefore, the study was powered to detect differences somewhat smaller than 0.5 SD.

Randomisation

Allocations were generated by computer using block randomisation with varying block sizes in advance of the study. A password-controlled secure database concealed the allocation until data had been entered to confirm identity and eligibility. Randomisation took place as close to the start of surgery as possible. The team member responsible for randomisation was not involved in data collection for the study.

Blinding

Participants were blinded to treatment allocation. The surgical team involved in the operation were unblinded. Research nurses collecting post-operative data, and assessors measuring wall thickness and lumen diameter with IVUS and quantitative angiography were blinded to treatment allocation. Laboratory staff conducting histological analyses of short segments of prepared vein could not be blinded to the harvest technique used.