Pre-operative 5-Aminolevulinic Acid to Activate Haem Oxygenase to Improve Outcomes in Cardiac Surgery: A Dose Finding Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Change from baseline HO-1 expression to time of cardiac surgery
研究概览
简要总结
TALEN is a prospective randomised double-blind placebo-controlled phase 2 study of 5-Aminolevulinic Acid with Sodium Ferrous Citrate (5-ALA-SFC) in adult patients undergoing cardiac surgery on cardiopulmonary bypass (CPB). TALEN aims to identify the optimal biological dose (OBD) of 5-ALA-SFC.
详细描述
TALEN is a prospective, randomised, double blind, placebo-controlled phase 2 study of 5-ALA-SFC administration in adults undergoing non-emergent cardiac surgery on CPB examining the potential of 5-ALA-SFC to induce haem oxygenase-1 (HO-1) as a novel cardio- and cyto-protective strategy for clinical benefit. 5-ALA is an amino acid found in several foods and a natural endogenous precursor in the synthesis of haem. Oral administration of 5-ALA-SFC has been shown to be safe and to induce a pharmacodynamic effect on the key effector, HO-1. TALEN is designed as a dose-finding trial with sequential dose cohorts, evaluating the safety, tolerability and PD response to 5-ALA-SFC to determine the optimum biological dose for further evaluation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Randomisation will follow a sequential randomisation list prepared by the blinded trial statistician. As participants are randomised, they will be manually allocated the next available treatment kit (active or placebo) number from this list which will correspond to the randomisation number.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Scheduled for non-emergent cardiac surgery under CPB (including coronary artery bypass grafting, valve replacement, valve repair or a combination thereof)
- •Signed informed consent
- •Age ≥18 years
- •Able and willing to comply with all study requirements
排除标准
- •Female participants who are of childbearing potential who are either unable or unwilling to use highly effective contraception, or who are pregnant or breast feeding
- •History of hypersensitivity to 5-ALA, SFC and/or porphyrins
- •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
- •Use of other investigational medical product(s) < 28 days prior to study or 5 half-lives, whichever is longer
- •Cardiogenic shock/Low cardiac output syndrome requiring catecholamine infusion and/or mechanical circulatory support prior to induction of anaesthesia for cardiac surgery
- •Recent acute myocardial infarction
- •Cardiac surgery without cardiopulmonary bypass or induced fibrillating heart surgery
- •Inadequate renal or liver function
- •Any other condition which, in the opinion of the Investigator, makes the patient unsuitable for or may compromise their participation in the study
研究组 & 干预措施
Cohort 2
150 mg 5-ALA with 236 mg SFC or bd for three days before surgery (n=8 patients)
干预措施: Sodium ferrous citrate (SFC) (Drug)
Cohort 1
75 mg 5-ALA with 118 mg SFC bd (lowest/starting dose) for three days before surgery (n=8 patients)
干预措施: 5-Aminolevulinic Acid hydrochloride (5-ALA) (Drug)
Cohort 1
75 mg 5-ALA with 118 mg SFC bd (lowest/starting dose) for three days before surgery (n=8 patients)
干预措施: Sodium ferrous citrate (SFC) (Drug)
Cohort 2
150 mg 5-ALA with 236 mg SFC or bd for three days before surgery (n=8 patients)
干预措施: 5-Aminolevulinic Acid hydrochloride (5-ALA) (Drug)
Cohort 3
225 mg 5-ALA with 354 mg SFC bd for three days before surgery (n=8 patients)
干预措施: 5-Aminolevulinic Acid hydrochloride (5-ALA) (Drug)
Cohort 3
225 mg 5-ALA with 354 mg SFC bd for three days before surgery (n=8 patients)
干预措施: Sodium ferrous citrate (SFC) (Drug)
Cohort 4
300 mg 5-ALA with 472 mg SFC bd (maximum dose) for three days before surgery (n=8 patients)
干预措施: 5-Aminolevulinic Acid hydrochloride (5-ALA) (Drug)
Cohort 4
300 mg 5-ALA with 472 mg SFC bd (maximum dose) for three days before surgery (n=8 patients)
干预措施: Sodium ferrous citrate (SFC) (Drug)
Placebo
2 patients in each cohort above will be allocated to placebo (n=8 patients in total across the study)
干预措施: Placebo (Other)
结局指标
主要结局
Change from baseline HO-1 expression to time of cardiac surgery
时间窗: Baseline at screening compared to post dose (measured within 12 hours of final dose, before cardiac surgery)
Normalised HO-1 expression in peripheral blood •Safety: Occurrence of adverse events / laboratory safety events defined as dose-limiting toxicity (DLTs)
Number of Participants With Dose Limiting Toxicity
时间窗: Up to 72 hours post-surgery
次要结局
- Incidence of treatment related emergent AEs [safety and tolerability](From time of administration of placebo or investigational medicinal product (IMP) (i.e. treatment-emergent AEs, TEAEs) to 72 hours post-operatively)
- Change from baseline HO activity to time of cardiac surgery(Baseline at screening compared to post dose (measured within 12 hours of final dose, before cardiac surgery))
- Preliminary evaluation of the kinetics of peri-operative myocardial injury(Serial measurements until 72 hours after release of aortic cross clamping)