Clinical trial NCT01398384: Effects of Nitric Oxide for Inhalation in Myocardial Infarction Size
Official title: The Effects of Nitric Oxide for Inhalation on Myocardial Infarction Size
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myocardial Infarction
Keywords: ST Elevation MI
STEMI
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2011-07-20
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Myocardial infarction size as a fraction of left ventricular size
timeFrame: 48-72 hours
Secondary outcomes:
measure: MI size, extent and transmurality of microvascular obstruction
timeFrame: 48-72 hours
measure: MI size normalized to area at risk
timeFrame: 48-72 hours
measure: Myocardial perfusion at coronary angiography at the completion of PCI (corrected TIMI frame count and myocardial blush grade).
timeFrame: at completion of PCI, as expected 1 day
measure: Transmurality of infarct (as average percent wall thickness in all segments showing delayed enhancement).
timeFrame: at 48 - 72 hours and 4 months
measure: Myocardial perfusion(MRI).
timeFrame: at 48-72 hours and 4 months
measure: 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.
timeFrame: 48-72 hours and 4 months
measure: 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.
timeFrame: at 4 hours
measure: Troponin T levels and CPK-MB area under the curve at 48 hours.
timeFrame: 48 hours
measure: 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.
timeFrame: 4 months
measure: 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.
timeFrame: 4 months
measure: Assess the safety of inhaled NO for this use as determined by reported adverse events (including bleeding and laboratory changes).
timeFrame: during treatment gas period, an average of 6 hours
Other outcomes:
Locations:
city: Hasselt
country: Belgium
facility: Jessa Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
city: Budapest
country: Hungary
facility: Semmelweis University Heart Center
city: Krakow
country: Poland
facility: John Paul II Hospital
Study officials:
affiliation: UZ Leuven
name: Stefan Janssens, Prof Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: UZ Leuven
name: Frans Van de Werf, Prof Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.