Clinical trial NCT07027670: Treatment With 5-AminoLEvuliNic Acid Before Cardiac Surgery
Official title: Pre-operative 5-Aminolevulinic Acid to Activate Haem Oxygenase to Improve Outcomes in Cardiac Surgery: A Dose Finding Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiac Surgical Procedures
Coronary Artery Bypass
Aortic Valve Disease
Mitral Valve Disease
Keywords: heme oxygenase
cardiopulmonary bypass
HO-1
aortic valve replacement
mitral valve surgery
5-aminolevulinic acid
delta aminolevulinic acid
sodium ferrous citrate
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: SBI Pharmaceuticals Co, Ltd.
name: George Clinical Pty Ltd
First posted: 2025-06-18
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Sequential dose escalation cohorts of 10 evaluable patients each (8 on active:2 on placebo) dosed twice daily (bd) with 5-ALA-SFC or placebo for three pre-operative days and once on the day of cardiac surgery. Up to 4 discrete dose levels are anticipated.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change from baseline HO-1 expression to time of cardiac surgery
timeFrame: Baseline at screening compared to post dose (measured within 12 hours of final dose, before cardiac surgery)
measure: Number of Participants With Dose Limiting Toxicity
timeFrame: Up to 72 hours post-surgery
Secondary outcomes:
measure: Incidence of treatment related emergent AEs [safety and tolerability]
timeFrame: From time of administration of placebo or investigational medicinal product (IMP) (i.e. treatment-emergent AEs, TEAEs) to 72 hours post-operatively
measure: Change from baseline HO activity to time of cardiac surgery
timeFrame: Baseline at screening compared to post dose (measured within 12 hours of final dose, before cardiac surgery)
measure: Preliminary evaluation of the kinetics of peri-operative myocardial injury
timeFrame: Serial measurements until 72 hours after release of aortic cross clamping
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
state: Oxfordshire
Study officials:
affiliation: University of Oxford
name: Arash Yavari, DPhil MRCP
role: PRINCIPAL_INVESTIGATOR
References: