Clinical Trials Register

Summary
EudraCT Number:	2015-001321-17
Sponsor's Protocol Code Number:	11275
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2016-08-31
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2015-001321-17

A.3

Full title of the trial

A randomised control trial of 5-Aminolevulinic Acid in combination with Sodium Ferrous Citrate to Enhance Cardioprotection in Adults undergoing Cardiac Surgery

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Does 5-Aminolevulinic acid in combination with sodium ferrous citrate improve the strength of the heart beat following surgery using a heart lung machine?

A.3.2

Name or abbreviated title of the trial where available

Trial of 5-Aminolevulinic Acid to Enhance Cardioprotection (TALEN)

A.4.1

Sponsor's protocol code number

11275

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University of Oxford
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Oxford
B.5.2	Functional name of contact point	Prof Houman Ashrafian
B.5.3	Address:
B.5.3.1	Street Address	Radcliffe Department of Medicine
B.5.3.2	Town/ city	Level 6, West Wing, John Radcliffe Hospital
B.5.3.3	Post code	OX3 9DU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01865 234670
B.5.5	Fax number	01865 234658
B.5.6	E-mail	houman.ashrafian@cardiov.ox.ac.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Gliolan
D.2.1.1.2	Name of the Marketing Authorisation holder	Medac Gesellschaft für klinische Spezialpräparate mbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	131371
D.3 Description of the IMP
D.3.1	Product name	5-Aminolevulinic acid
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	5-Aminolevulinic acid
D.3.9.1	CAS number	5451-09-2
D.3.9.3	Other descriptive name	5-Amino-4-oxopentanoic acid hydrochloride
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	5-Aminolevulinic acid
D.3.9.1	CAS number	5451-09-2
D.3.9.3	Other descriptive name	5-Amino-4-oxopentanoic acid hydrochloride
D.3.9.4	EV Substance Code	AS5
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.4	EV Substance Code	AS6
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	N/A
D.2.1.1.2	Name of the Marketing Authorisation holder	Quantum Generics
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Sodium Ferrous Citrate
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sodium Ferrous Citrate
D.3.9.1	CAS number	50717-86-7
D.3.9.3	Other descriptive name	Tetrasodium biscitrato iron (II)
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	117.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sodium Ferrous Citrate
D.3.9.1	CAS number	50717-86-7
D.3.9.3	Other descriptive name	Tetrasodium biscitrato iron (II)
D.3.9.4	EV Substance Code	AS3
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	235
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.4	EV Substance Code	AS4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Low cardiac output states following cardioplegic arrest for cardiac surgery

E.1.1.1

Medical condition in easily understood language

Weakened heart beat following surgery using a heart lung machine

E.1.1.2

Therapeutic area

Body processes [G] - Cell Physiological Phenomena [G04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	HLT
E.1.2	Classification code	10007602
E.1.2	Term	Cardiac and vascular procedural complications
E.1.2	System Organ Class	100000004863

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10051624
E.1.2	Term	Myocardial reperfusion injury
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10066123
E.1.2	Term	Cardiopulmonary bypass
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10024920
E.1.2	Term	Low output state
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Does 5-Aminolevulinic acid in combination with sodium ferrous citrate improve the performance of the heart following surgery which required stopping of the heart and use of a heart lung machine?

E.2.2

Secondary objectives of the trial

Does 5-Aminolevulinic acid in combination with sodium ferrous citrate reduce the amount of heart tissue damaged by stopping the heart and using the heart lung machine as measured by chemical markers of heart cell damage in the blood?
Does 5-Aminolevulinic acid in combination with sodium ferrous citrate reduce the proportion of patients who require a pump to be inserted into the main blood vessel down the centre of their body to support their heart following surgery that require the use of the heart lung machine?
Do patients who receive 5-Aminolevulinic acid in combination with sodium ferrous citrate need less medications to support their blood pressure and help their heart to beat more forcefully after their operation?
Does 5-Aminolevulinic acid in combination with sodium ferrous citrate reduce the damage to other organs, for example the kidneys, which results from the weakening of the heart due to stopping it and using heart lung machine?
Does 5-Aminolevulinic acid in combination

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Undergoing on-pump cardiac surgery. Procedure must be: Coronary artery by-pass grafting, Aortic valve replacement/repair or combination of both.
• Participant is willing and able to give informed consent for participation in the trial.
• Male or Female, aged 18 years or above.
• In the Investigator’s opinion, is able and willing to comply with all trial requirements.
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial.

E.4

Principal exclusion criteria

• Female participant who is pregnant or lactating.
• Porphyria or family history of porphyria
• Haemochromatosis
• Past history of photosensitization
• Current use of photo-sensitising medications e.g. tetracyclines, sulfonamides, fluoroquinolones
• Current use of Fluoroquinolones, hypericin extract or iron replacement therapy
• Known sensitivity to 5-ALA or SFC
• Involvement in another trial of an investigational medical product within the past month
• Intention to perform other cardiac procedures and surgery for catastrophic events
• Emergency cases where 3-days pre-treatment is not possible

E.5 End points

E.5.1

Primary end point(s)

Reduction in the incidence of low cardiac output state (LCOS) 6 hours post cessation of cardiopulmonary bypass. LCOS defined a priori as a cardiac index of <2.2 L. min-1. m-2 refractory to appropriate intravascular volume expansion after correction or attempted correction of any dysrhythmias

E.5.1.1

Timepoint(s) of evaluation of this end point

6 hours post cessation of cardiopulmonary bypass

E.5.2

Secondary end point(s)

Area under the curve of Troponin T release
Gross inotrope requirement
Requirement of intra-aortic balloon pump support
Incidence of acute kidney injury
Length of stay
Mortality
Differences in cardiomyocyte proteomics related to ischaemia-reperfusion response

E.5.2.1

Timepoint(s) of evaluation of this end point

At discharge

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of trial will be the date of discharge of the last participant. At the end of the study the patient’s usual treatment and care will continue exactly as that of a patient who had not participated in the study.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1