Clinical Trials Register

Summary
EudraCT Number:	2007-002931-95
Sponsor's Protocol Code Number:	LCC2010.01
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2007-11-08
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2007-002931-95

A.3

Full title of the trial

The Effects of Nitric Oxide for Inhalation on Myocardial Infarction Size.

A.3.1

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

Is breathing a new medical gas better than oxigen in protecting your heart after a heart attack?

A.3.2

Name or abbreviated title of the trial where available

NOMI

A.4.1

Sponsor's protocol code number

LCC2010.01

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	UZ Leuven
B.1.3.4	Country	Belgium
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	Institute for Science and Technology
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	UZ Leuven
B.5.2	Functional name of contact point	Leuven Coordinating Centre
B.5.3	Address:
B.5.3.1	Street Address	Herestraat 49
B.5.3.2	Town/ city	Leuven
B.5.3.3	Post code	3000
B.5.3.4	Country	Belgium
B.5.4	Telephone number	3216342114
B.5.5	Fax number	3216342100
B.5.6	E-mail	katleen.vandenberghe@uzleuven.be

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	VASOkinox 450 ppm (nitric oxide) for inhalation
D.2.1.1.2	Name of the Marketing Authorisation holder	Air Liquide Santé International
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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	VASOkinox 450 ppm (nitric oxide) for inhalation
D.3.2	Product code	n/a
D.3.4	Pharmaceutical form	Inhalation gas
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	nitric oxide
D.3.9.1	CAS number	10102-43-9
D.3.9.2	Current sponsor code	n/a
D.3.9.3	Other descriptive name	n/a
D.3.10	Strength
D.3.10.1	Concentration unit	PPM part per million
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	450
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	Yes
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	Inhalation gas
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Myocardial Infarction

E.1.1.1

Medical condition in easily understood language

Acute heart attack

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	PT
E.1.2	Classification code	10028596
E.1.2	Term	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 primary objective of the trial is to assess whether or not inhaled nitric oxide can decrease myocardial infarction (MI) size as a fraction of left ventricular (LV) size at 48-72 hours in patients presenting with an ST segment elevation MI who undergo successful percutaneous coronary intervention.

E.2.2

Secondary objectives of the trial

The secondary objectives of the trial are to assess impact of NO inhalation on:
1. MI size at 48–72 h (MRI).
2. MI size normalized to area at risk at 48–72 h (MRI).
3. Myocardial perfusion after PCI.
4. MI transmurality at 48–72 h and 4 months.
5. Myocardial perfusion at 48-72 h and 4 months (MRI).
6. Global & regional left ventricular (LV) function and LV mass at 48–72 h and 4 months after MI. MI size as a fraction of LV size at 4 months after MI.
7. Resolution of ST segment elevation at 4 h compared to enrollment.
8. Troponin T levels & CPK-MB area under the curve at 48 h.
9. Change between 48-72 h and 4 months in LV end-diastolic volume; end-systolic volume; end-diastolic myocardial wall thickness in infarct, peri-infarct & remote areas; & sphericity index at end-diastole & end-systole.
10. Death; nonfatal recurrent MI; recurrent ischemia necessitating re-hospitalization, PCI, or surgical revascularization; & stroke at 4 months.
11. Safety-determined by reported AEs.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The patient must meet the following criteria:
1. Acute myocardial infarction (defined as an episode of chest pain or related symptom lasting greater than 2 hours but less than 12 hours and electrocardiographic evidence of ST elevation (measured as 0.08 seconds after the J point; sum >= 0.6 mV in leads I, II, III, AVL, AVF, V1-V6).
2. No evidence of congestive heart failure (no S3 or evidence of pulmonary edema) and normal oxygen saturation on ≤ 2L oxygen by NC.
3. Age > 18 years.
4. Signed EC approved informed consent.

E.4

Principal exclusion criteria

The patient will be excluded from enrollment if any of the following are true:
1. Prior myocardial infarction (as determined by patient history and/or ECG), cardiac surgery, or severe pericardial, congenital, cardiomyopathic or valvular heart disease.
2. Requirement for urgent cardiac surgery.
3. Previous CABG or PCI.
4. Left bundle branch block.
5. Unable to tolerate magnetic resonance imaging (including disallowed metallic implants or BMI > 35) or unable to tolerate gadolinium contrast media, including patients with calculated creatinine clearance less than 60 ml/min/1.73 m2 BSA.
6. Active or recent hemorrhage requiring an invasive procedure for evaluation or transfusion within 6 weeks prior to presentation or hemorrhagic stroke within the 6 weeks prior to presentation.
7. Known or suspected aortic dissection.
8. Prior history of pulmonary disease requiring chronic oxygen therapy.
9. Pregnancy, lactating and woman of childbearing potential.
10. Use of investigational drugs or device within the 30 days prior to enrollment to the study. Investigational uses of approved therapies will be allowed.
11. Medical problem likely to preclude completion of the study.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable for this study will be myocardial infarction size as a fraction of left ventricular size as measured by contrast-enhanced cardiac MRI.

E.5.1.1

Timepoint(s) of evaluation of this end point

at 48-72 hours

E.5.2

Secondary end point(s)

1. MI size, extent and transmurality of microvascular obstruction at 48 –
72 hours (MRI).
2. MI size normalized to area at risk at 48 – 72 hours (MRI).
3. Myocardial perfusion at coronary angiography at the completion of
PCI (corrected TIMI frame count and myocardial blush grade).
4. Infarct transmurality (as average percent wall thickness in all
segments showing delayed enhancement) at 48 – 72 hours and 4
months.
5. Myocardial perfusion at 48 – 72 hours and 4 months (MRI).
6. Global and regional left ventricular function and left ventricular mass
at 48 – 72hours and 4 months after MI, and the change in global LV
function and mass between 48 – 72 hours and 4 months. MI size as a
fraction of LV size at4 months after MI.
7. Resolution of ST segment elevation (serial ECGs) as indicated by the
decrease in the total ST elevation (in mV) at 4 hours compared with that
observed at enrollment.
8. Troponin T levels and CPK-MB area under the curve at 48 hours.
9. Change in adverse remodeling parameters at 4 months (compared
with 48 – 72 hours): changes in LV end-diastolic volume, end-systolic
volume, end-diastolic myocardial wall thickness in infarct, peri-infarct
and remote areas and in sphericity index at end-diastole and endsystole.
10. Incidence of death; nonfatal recurrent myocardial infarction;
recurrent ischemia necessitating re-hospitalization, PCI, or surgical
revascularization; and stroke (i.e. combined CV endpoint) at 4 months.
Enzyme leak during subsequent scheduled PCI will not be considered
new ischemia/MI.
11. Assess the safety of inhaled NO for this use as determined by
reported adverse events (including bleeding and laboratory changes).

E.5.2.1

Timepoint(s) of evaluation of this end point

48-72 hours and at 4 months

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

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

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

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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

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.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

138

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

130

F.4.2

For a multinational trial

F.4.2.1

In the EEA

230

F.4.2.2

In the whole clinical trial

230

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2007-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-01-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-05-01

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