Treatment With 5-AminoLEvuliNic Acid Before Cardiac Surgery (TALEN)

University of Oxford

Status and phase: Completed; Phase 2

Conditions: Mitral Valve Disease; Aortic Valve Disease; Coronary Artery Bypass; Cardiac Surgical Procedures

Treatments: Drug: Sodium ferrous citrate (SFC); Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA); Other: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07027670

280513

Details and patient eligibility

About

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.

Full 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.

Enrollment: 48 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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48 participants in 5 patient groups, including a placebo group

Cohort 1

Experimental group

Description:

75 mg 5-ALA with 118 mg SFC bd (lowest/starting dose) for three days before surgery (n=8 patients)

Treatment:

Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA)

Drug: Sodium ferrous citrate (SFC)

Cohort 2

Experimental group

Description:

150 mg 5-ALA with 236 mg SFC or bd for three days before surgery (n=8 patients)

Treatment:

Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA)

Drug: Sodium ferrous citrate (SFC)

Cohort 3

Experimental group

Description:

225 mg 5-ALA with 354 mg SFC bd for three days before surgery (n=8 patients)

Treatment:

Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA)

Drug: Sodium ferrous citrate (SFC)

Cohort 4

Experimental group

Description:

300 mg 5-ALA with 472 mg SFC bd (maximum dose) for three days before surgery (n=8 patients)

Treatment:

Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA)

Drug: Sodium ferrous citrate (SFC)

Placebo

Placebo Comparator group

Description:

2 patients in each cohort above will be allocated to placebo (n=8 patients in total across the study)

Treatment:

Other: Placebo