A randomised Placebo-contROlled Trial of Ad5.CMVTO.TIMP-3 to prEvent Coronary artery bypass grafT failure
Vein graft blocking in those having a Heart Bypass Surgery to address Heart Disease symptoms, such as chest pain and shortness of breath
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 grafts’. The surgeon will harvest a saphenous vein from the leg, and divide the vein into two or three segments for use as grafts. During the surgery, the saphenous veins are connected to the aorta and the coronary arteries to ‘bypass’ blockages. Patients who undergo CABG surgery have an appreciable likelihood of developing recurrent angina and experiencing a heart attack in the longer term. Although the artery graft works well life-long, on exposure to arterial levels of blood pressure, the vein grafts undergo maladaptive remodelling in the longer term. Each of the 2 Vein segments will receive 30 min exposure to either; 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 that each participant that receives a vein treated with active gene therapy will also receive a vein treated with a placebo, therefore each participant acts as their own treated versus placebo comparison.
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
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. Unwilli