Cardioprotection for coronary artery bypass graft surgery MedDRA version: 20.0 Level: LLT Classification code 10017501 Term: Functional disturbances following cardiac surgery System Organ Class: 100000004863 MedDRA version: 20.0 Level: HLT Classification code 10007602 Term: Cardiac and vascular procedural complications System Organ Class: 100000004863 MedDRA version: 21.1 Level: PT Classification code 10066123 Term: Cardiopulmonary bypass System Organ Class: 10042613 - Surgical and medical pr
Conditions
Interventions
Trade Name: Gliolan
Product Name: Gliolan
Pharmaceutical Form: Capsule
INN or Proposed INN: 5-Aminolevulinic acid
CAS Number: 5451-09-2
Other descriptive name: 5-Amino-4-oxopentanoic acid hydrochlorid
Sponsors
University of Oxford / Clinical Trials and Research Governance
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age > 18 years • Scheduled for primary, isolated elective (non-emergent) CABG under cardiopulmonary bypass • Signed informed consent • Able and willing to comply with all study requirements Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: • Female participants who are pregnant, or breast feeding, or either unable or unwilling to use highly effective contraception if of child-bearing potential (under 55 years) • Acute or chronic types of porphyria • Known genetic haemochromatosis or clinically significant iron overload • History of clinically significant photosensitization • Current long-term (> 3 months) use of amiodarone • Concomitant use of hypericin extract (including St John’s Wort) or concomitant therapeutic dose oral iron replacement • History of allergic or adverse reaction to 5-ALA and/or SFC • Use of other investigational medical product(s) ULN together with symptoms of myocardial ischaemia and/or new ischaemic ECG changes within 2 weeks of surgery • Coronary surgery without cardiopulmonary bypass (i.e. off pump/OP-CABG) or induced fibrillating heart surgery • Inadequate renal or liver function defined as any of: o estimated glomerular filtration rate (eGFR) 2.5 x ULN o total bilirubin > 2 x ULN (unless documented Gilbert’s syndrome) o known cirrhosis o known active hepatitis infection • Any other condition which, in the opinion of the investigator, which makes the patient unsuitable for or may compromise their participation in the study, e.g. due to safety concerns or compliance with clinical study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the optimum dose of 5-ALA to safely activate the cytoprotective molecule haem oxygenase-1 (HO-1) administered pre-operatively to patients undergoing CABG surgery. ;Secondary Objective: To evaluate how well-tolerated different doses of 5-ALA with sodium ferrous citrate (SFC) are in patients undergoing CABG surgery and identify the optimal dose based on how well it activates its target protective enzyme, HO-1. Other questions this research study is designed to address include seeing whether 5-ALA can reduce the harmful effects of breakdown of red blood cells (haemolysis) that occurs during cardiac surgery. The study will also measure the inflammatory response to cardiac surgery and see whether 5-ALA can reduce this. The study will also examine whether normal genetic variation in HO-1 affects the response to 5-ALA (such as making it more or less effective).;Primary end point(s): Change in HMOX1 mRNA expression (i.e. the target of 5-ALA which encodes the cytoprotective HO-1 protein) measured from peripheral blood mononuclear cells (PBMCs).;Timepoint(s) of evaluation of this end point: At baseline –(i.e.after randomisation but before taking 5-ALA with SFC or placebo) and at the end of the oral dosing period prior to CABG surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To (a) characterise the safety and tolerability profile of 5- ALA with sodium ferrous citrate and (b) to determine the pharmacodynamic response (change in HO-1 protein expression in PBMCs).;Timepoint(s) of evaluation of this end point: A. From before the administration of the first IMP / placebo dose until 72 hours post-operatively B. At baseline – (i.e.after randomisation but before taking 5-ALA with SFC or placebo) and at the end of the oral dosing period prior to CABG surgery. | — |
Countries
United Kingdom
Contacts
Public ContactArash Yavari
University of Oxford
Outcome results
None listed