Clinical Trials Register

Summary
EudraCT Number:	2010-023211-34
Sponsor's Protocol Code Number:
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-02-03
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

2010-023211-34

A.3

Full title of the trial

Randomized Controlled Trial Comparing Intracoronary Administration
of Adenosine or Sodium Nitroprusside to Control for Attenuation of Microvascular
Obstruction During Primary Percutaneous Coronary Intervention

A.3.1

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

MVO Study

A.3.2

Name or abbreviated title of the trial where available

MVO 09/150/28

A.4.1

Sponsor's protocol code number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University Hospitals of Leicester NHS Trust
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor
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
B.5.2	Functional name of contact point

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	Adenocor
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-aventis
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	Adenosine
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intracoronary use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Adenosine
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3 to 1
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.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	Nitroprussiat Fides
D.2.1.1.2	Name of the Marketing Authorisation holder	Rottapharm
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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 Nitroprusside
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intracoronary use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sodium Nitroprusside
D.3.9.1	CAS number	13755-38-9
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
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	50
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute ST-segment Elevation Myocardial Infarction

E.1.1.1

Medical condition in easily understood language

Heart attack where the coronary artery is completely blocked off by the blood clot, and as a result virtually all the heart muscle being supplied by the affected artery starts to die.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10041894
E.1.2	Term	ST segment elevation
E.1.2	System Organ Class	10022891 - Investigations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10000891
E.1.2	Term	Acute myocardial infarction
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

The principal objective of our proposed study is to determine:-
1) Whether adjunctive medical treatment given via a very small tube placed beyond the blockage downstream in the affected heart attack artery at time of angioplasty for heart attack and following blood clot removal from the heart vessel, reduces downstream small blood vessel obstruction and heart muscle damage size as determined by using CMR scanners.
The principal study question is:
1) How might we attenuate small blood vessel obstruction and thus reduce heart attack size in patients undergoing angioplasty for heart attack?

E.2.2

Secondary objectives of the trial

The secondary objectives of our proposed study are to determine:-
1) Whether there is a difference between the small downstream artery dilating drugs -adenosine and sodium nitroprusside in their ability to reduce small blood vessel obstruction and heart muscle damage size determined using CMR scanners, both given via a very small tube (catheter) placed beyond the blockage in the downstream affected heart artery.
2) The correlation of markers of poor blood flow in heart vessels as determined by the flow seen on the angiogram, with CMR detected small blood vessel obstruction and heart muscle damage, as well as with clinical outcome at six months.
The secondary study questions are:
1) Should all,some or no patients receive adjunctive therapies (adenosine / sodium nitroprusside) given via a small tube (catheter) to reduce small downstream blood vessel obstruction routinely in addition to the standard current treatment of blood clots removal(aspiration) from the heart's artery and if so

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Title:Assessment of platelet activation and inflammation during the procedures. See Full protocol Version 5, Date: 04/11/11, Page 14.

This mechanistic sub-study will be carried out on patients entered into the study at Glenfield hospital (Leicester), and will be performed in Professor Goodall’s laboratory by the Clinical Fellow, using established methods, and with support from experienced technical staff.

Objective: Small samples of blood (≤2ml) will be taken from the patients to assess the effect of these short lived treatment agents on platelet activation within the coronary circulation.

E.3

Principal inclusion criteria

• ≥ 18 years age with written informed ASSENT prior to angiography. (ASSENT is being used following Ethical Committee approval in another trial run by University Hospitals of Leicester- The STREAM study).
• ST – segment elevation myocardial infarction (STEMI) ≤ 6 hrs of symptom onset requiring primary reperfusion by PCI.
• Single-vessel and coronary artery disease (non culprit disease ≤70% stenosis at angiography) to avoid bias which may occur in analysis of microvascular obstruction (MVO) and infarct size if intervention should be undertaken in more than one vessel.
• TIMI flow 0/I at angiography.

E.4

Principal exclusion criteria

• Any exclusion criteria for primary percutaneous coronary intervention (P-PCI) (see below).
• Previous Q wave myocardial infarction.
• Contraindications to cardiac MRI contrast agents, or study medications: Aspirin, Prasugrel, Bivalirudin.
• Cardiogenic Shock or systolic blood pressure ≤ 90mmHg needing intraortic balloon pump.
• Culprit lesion located in a by-pass graft.
• Culprit lesion non identified.
• Stent thrombosis.
• Left main disease.
• Known severe asthma.
• Known stage 4 or 5 chronic kidney disease (eGFR<30ml/min).
• Pregnancy.
Exclusion criteria for P-PCI: presentation timing, inadequate arterial access, patient unable to tolerate PCI procedure(in operators’ opinion).
Absolute contra-indication to cardiac MRI (Pacemaker, Implantable cardiac defibrillator, intra-cranial metal clips).

E.5 End points

E.5.1

Primary end point(s)

Cardiac magnetic resonance (CMR) measured infarct size (%LV mass) at 48-72 hours post procedure. Infarct size has been chosen rather than the microvascular obstruction (MVO) as the primary end point since there is a wealth of published data on infarct size following P-PCI. We are also uncertain as to the expected size of effect on MVO (incidence and absolute reduction in MVO as % of LV mass) of both sodium nitroprusside and adenosine. MVO and infarct size measured on CMR are closely inter-related and are both important predictors of prognosis.

E.5.2

Secondary end point(s)

1. CMR incidence and extent of MVO (% LV mass)at 48-72 hours post procedure.
2. CMR measured myocardial salvage index, haemorrhage, LV EF and volumes in the acute stage.
3. Angiographic markers of MVO including the recently designed computer-assisted myocardial blush quantification ‘Quantitative Blush Evaluator’ (QuBE)(83). (Assessed by two interventional cardiologists blinded to treatment arm).
4. Incidence pre and post procedure angiographic true “no-reflow”.
5. Incidence of angiographic slow/no-reflow after PCI with the three different management strategies.
6. Any in-patient clinical events (re-occlusion), need for repeat PCI, recurrent chest pain with new ECG changes, incidence of clinical heart failure (symptoms plus basal crackles plus X-ray evidence pulmonary congestion) proven cerebrovascular accident (CVA).
7. Overall MACCE and its components at 6 months: namely death, need for TLR, recurrent MI, severe heart failure, and CVA.
8. Comparing CMR markers with other myocardial perfusion markers: angiographic (TIMI grade CTFC, MBG, and computer-assisted myocardial blush quantification), ECG (ST segment resolution) and cardiac enzymes.
9. Degree of ST resolution.
10. Echocardiography assessment of LV (EDV, ESV and EF) at 8-12 weeks during a routine follow up visit.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

standard clinical care

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

Yes

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

last patient last visit / telephone interview

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