Vein graft blocking in those having a Heart Bypass Surgery to address Heart Disease symptoms, such as chest pain and shortness of breath Surgery
Conditions
Interventions
Coronary artery bypass graft (CABG) is recommended for the treatment of multivessel and/or left main obstructive coronary atherosclerosis (fatty plaque). Typically, the CABG operation involves ‘bypass
gene therapy -Adenovirus tissue inhibitor of matrix metalloproteinase – 3 or placebo media. Saphenous vein segments will be treated depending on the cohort the participant is recruited to. This means
Sponsors
NHS Greater Glasgow and Clyde
University of Glasgow
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Referral for planned CABG surgery anticipated to involve one mammary artery graft and two or more saphenous vein grafts. 2. Willingness to comply with all trial-related procedures and visits as defined in the protocol 3. Written informed consent
Exclusion criteria
Exclusion criteria: 1. Requirement for immunosuppressive drug therapy at any time during the past 3 months; whether administered orally, subcutaneously or intravenously. This would include corticosteroids (but not inhaled or topical), drugs used following transplantation (e.g. tacrolimus, cyclosporine), anti-metabolite therapies (e.g. mycophenolic acid (Myfortic), azathioprine, leflunomide (Arava)), and immunomodulators including biologics (e.g. adalimumab, etanercept, aldesleukin), and conventional and targeted synthetic DMARDs (cyclophosphamide, methotrexate, baracitinib etc). Please note this list is not exhaustive and a requirement for other immunosuppressive drugs not listed would also exclude the patient and must be discussed with the Sponsor. 2. Active or prophylactic treatment with oral or parenteral antibiotic, antifungal or antiviral therapy to treat or prevent infection. 3. Anti-cancer treatment (excluding surgery) at any time during the past 3 months including chemotherapy, radiotherapy and treatment with biologics such as Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors (e.g. bevacizumab, pazopanib), targeted chemotherapy drugs e.g. protein kinase inhibitors, and cell-based therapy e.g immunotherapy. This list is not exhaustive and sponsor or CI should be contacted for advice if required. 4. Previously enrolled in a gene therapy or cell therapy trial. 5. Liver disease with a Child-Pugh score of A (5-6 points) or higher. See Appendix 3* 6. Women who are pregnant, breast-feeding or of child-bearing potential (WoCBP). 7. Men who are sexually active with a WoCBP who are unwilling to use condoms or other highly effective methods of contraception for the duration of study treatment and for 12 weeks after dosing. 8. Participation in another intervention study involving a drug within the past 90 days or 5 half-lives whichever is longer (co-enrolment in observational studies is permitted). 9. Incapacity or inability to provide informed consent. 10. Unwillingness to comply with all trial related procedures and visits defined in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events (TEAE) measured using an assessment of physical examinations (if indicated), changes in vital signs and ECGs, and analysis of clinical laboratory samples by the end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The following saphenous vein graft (SVG) measures will be assessed at 12 months: 1.1. SVG occlusion by CTCA at 12 months 1.2. SVG with diameter stenosis >50% 1.3. SVG with diameter stenosis >50% or occlusion 1.4. SVG revascularisation 2. Major adverse cardiovascular events: MACCE (death, re-hospitalisation for cardiovascular events including recurrent MI, heart failure); repeat revascularization of a native coronary artery or graft, as adjudicated by the SRC, measured using data collected in Case Report Forms until the end of the trial 3. Withdrawal rate, serious adverse event (SAE) rate measured using measured using data collected in Case Report Forms until the end of the trial 4. Efficacy - The within-subject difference between active therapy- and placebo-treated SVG including all available assessments measured using clinical data until the end of the trial 5. Patient-reported outcome measures (PROMs) measured using the EuroQol 5 Dimension (EQ-5D), Seattle Angina Questionnaire and the Duke Activity Status Index (DASI) at V2 (Pre CABG) and at V6 (6 weeks post-procedure) | — |
Countries
Scotland, United Kingdom
Contacts
Public ContactLisa Jolly
Outcome results
None listed