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.