Effects of Nitric Oxide for Inhalation in Myocardial Infarction Size (NOMI)

The Effects of Nitric Oxide for Inhalation on Myocardial Infarction Size

The purpose of this study is to determine the effects of Nitric Oxide for Inhalation on Myocardial Infarction Size.

Study Overview

• Status: Completed
• Conditions: Acute Myocardial Infarction
• Intervention / Treatment: Drug: Nitric Oxide; Drug: MI size at 48-72 hours

Detailed Description

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 size at 48-72 hours in patients presenting with an ST segment elevation MI who undergo successful percutaneous coronary intervention.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Hasselt, Belgium
    • Jessa Hospital
  • Leuven, Belgium, 3000
    • UZ Leuven
• Hungary
  • Budapest, Hungary, 1122
    • Semmelweis University Heart Center
• Poland
  • Krakow, Poland, 31-202
    • John Paul II Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion 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 greater or equal to 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. All patients must undergo successful percutaneous coronary intervention for TIMI 0 or 1 coronary flow with resulting TIMI 2 or 3 (residual stenosis less than 30% if stented and less than 50% if opened by balloon angioplasty).
4. Age > 18 years.
5. Signed EC approved informed consent.

Exclusion Criteria:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nitric Oxide; nitric oxide for inhalation	Drug: Nitric Oxide; MI size at 48-72 hours; Other Names: vasoKINOX 450
Placebo Comparator: Placebo; inhalation gas	Drug: MI size at 48-72 hours; Placebo gas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial infarction size as a fraction of left ventricular size	Myocardial infarction size as a fraction of left ventricular size at 48-72 hours in patients presenting with an ST segment elevation MI who undergo successful percutaneous coronary intervention.	48-72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MI size, extent and transmurality of microvascular obstruction	MI size, extent and transmurality of microvascular obstruction measured by MRI	48-72 hours
MI size normalized to area at risk		48-72 hours
Myocardial perfusion at coronary angiography at the completion of PCI (corrected TIMI frame count and myocardial blush grade).		at completion of PCI, as expected 1 day
Transmurality of infarct (as average percent wall thickness in all segments showing delayed enhancement).		at 48 - 72 hours and 4 months
Myocardial perfusion(MRI).		at 48-72 hours and 4 months
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 at 4 months after MI.		48-72 hours and 4 months
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.		at 4 hours
Troponin T levels and CPK-MB area under the curve at 48 hours.		48 hours
Change in adverse remodeling parameters (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.	Change in adverse remodeling parameters (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 end-systole.	4 months
Death, nonfatal recurrent MI, 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.		4 months
Assess the safety of inhaled NO for this use as determined by reported adverse events (including bleeding and laboratory changes).		during treatment gas period, an average of 6 hours

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Stefan Janssens, Prof Dr, UZ Leuven; Principal Investigator: Frans Van de Werf, Prof Dr, UZ Leuven

Publications and helpful links

General Publications

• Janssens SP, Bogaert J, Zalewski J, Toth A, Adriaenssens T, Belmans A, Bennett J, Claus P, Desmet W, Dubois C, Goetschalckx K, Sinnaeve P, Vandenberghe K, Vermeersch P, Lux A, Szelid Z, Durak M, Lech P, Zmudka K, Pokreisz P, Vranckx P, Merkely B, Bloch KD, Van de Werf F; NOMI investigators. Nitric oxide for inhalation in ST-elevation myocardial infarction (NOMI): a multicentre, double-blind, randomized controlled trial. Eur Heart J. 2018 Aug 1;39(29):2717-2725. doi: 10.1093/eurheartj/ehy232.

Helpful Links

• NOMI: Final Statistical Analysis Plan 19 May 2014

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: July 18, 2011
• First Submitted That Met QC Criteria: July 19, 2011
• First Posted (Estimate): July 20, 2011

Study Record Updates

• Last Update Posted (Estimate): May 21, 2014
• Last Update Submitted That Met QC Criteria: May 20, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: STEMI; ST Elevation MI
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: LCC2010.01