None listed
Conditions
Brief summary
The gold-standard revascularisation approach for patients with left main stem or multi-vessel coronary artery disease (CAD) is coronary artery bypass graft (CABG) surgery. Vasospasm, graft occlusion and ischaemia-reperfusion injury are complications that commonly arise and significantly impact upon CABG success-rates. Sildenafil is a type 5 phosphodiesterase inhibitor that has vasodilatory, antiplatelet and ischaemia-reperfusion injury-preventing properties. We hypothesise that these properties of sildenafil could be exploited in patients undergoing CABG by reducing vasospasm, graft occlusion and ischaemia-reperfusion injury complication-rates. The Sildenafil during CABG Operations to Reduce Endpoints for patients with Coronary ARtery Disease (SCORECARD) Project is a novel multi-centre double-blind randomised controlled trial concept in which the vasodilatory, antiplatelet and ischaemia-reperfusion injury-preventing properties of sildenafil will be investigated in elective patients undergoing CABG. However, a population sample that is of sufficient size and power must first be calculated so that a significant difference can be detected in the future trial. In this feasibility study, a phase II trial will be undertaken in order to establish the magnitude of the difference in outcomes between sildenafil-treated and placebo-treated groups. Two hundred patients admitted under either Auckland or Waikato District Health Board’s cardiothoracic service for elective CABG between 1 February 2017 and 1 February 2018 will be screened against inclusion and exclusion criteria. Patients will be randomised in a double-blind fashion to receive either a sildenafil- or placebo-drug regime. We will collect and compare preoperative and postoperative cardiac magnetic resonance images, transit time flowmetry data, postoperative serum troponin T levels in the first 48 hours and mortality-rates at 30 days. The results from Phase II of The SCORECARD Project will establish the magnitude of the difference in vasopasm, graft occlusion and ischaemia-reperfusion injury complication-rates between sildenafil-treated and placebo-treated groups. These data will allow for sample size calculations, which will ultimately dictate whether or not it is feasible to proceed with conducting Phase III of The SCORECARD Project.
Interventions
Patients who are randomised to the exposure group will receive sildenafil according to the following regime:
Day before CABG:
sildenafil 50 mg orally three times daily.
Day of CABG:
sildenafil 100 mg orally via nasogastric tube at time of commencement of median sternotomy immediately followed by a 25 mL normal saline flush.
sildenafil 50 mg orally at 22:00.
Postoperatively days 1-28:
sildenafil 50 mg orally three times daily. Sildenafil will be delivered orally but, where not possible (such as
Patients who are randomised to the exposure group will receive sildenafil according to the following regime: Day before CABG: sildenafil 50 mg orally three times daily. Day of CABG: sildenafil 100 mg orally via nasogastric tube at time of commencement of median sternotomy immediately followed by a 25 mL normal saline flush. sildenafil 50 mg orally at 22:00. Postoperatively days 1-28: sildenafil 50 mg orally three times daily. Sildenafil will be delivered orally but, where not possible (such as immediately postoperatively in the Cardiovascular Intensive Care Unit, will be given via nasogastric tube followed by a 25 mL normal saline flush. NB: Three 50 mg tablets will be reconstituted with a sweetened solution according to local processes in order to create a 75 mL solution, which is equivalent to 150 mg sildenafil. Patients will be given 25 mL of sildenafil solution three times daily. Cardiothoracic wards, Cardiovascular Intensive Care Units and patients will all be asked to retain empty patient bottles in the designated SCORECARD box, which will be collected by a SCORECARD Project investigator in order to measure adherence. Unused drug will be retained and, once accounted for by a SCORECARD Project investigator, will be given to the locality pharmacy for disposal according to local processes.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1) Patients who are undergoing CABG +/- valve replacement at Auckland or Waikato District Health Board. 2) Patients who are undergoing CABG +/- valve replacement between 1 February 2017 and 1 February 2018. 3) Patients who are recommended and offered elective CABG +/- valve replacement.
Exclusion criteria
Patients will not be eligible for recruitment if they meet any of the following exclusion criteria: 1) Creatinine clearance less than or equal to 30 mL·min-1. 2) Hepatic failure as determined by Child-Pugh class B or class C. 3) BP less than or equal to 90/50 mm·Hg. 4) Any previous open cardiac surgical procedure. 5) Any history of: - Pulmonary arterial hypertension. - Postural hypotension. - Non-arteritic anterior ischaemic optic neuropathy. - Hereditary degenerative retinal disorders such as retinitis pigmentosa. - Recent commencement or increases in alpha blocker dosages. - Current pregnancy or lactation. - Allergy to any component of ViagraTM tablet. 6) Any use of sildenafil citrate, tadalafil or vardenafil within the one month prior to enrolment. 7) Any use of glyceryl trinitrate within the previous 24 hours. 8) Concomitant use of isosorbide mononitrate. 9) Concomitant use of potent CYP 3A4 inhibitors: - Erythromycin. - Saquinavir. - Ketoconazole. - Itraconazole. - Ritonavir. 10) Presence of any metalware that precludes CMR-use. 11) Unable to provide informed consent. 12) Not eligible for public funding.
Outcome results
None listed