STEMIPhase 2ENAMORNCT00854711
Randomized Placebo-controlled Trial of Inhaled iNO in Acute ST-segment Elevation MI Treated by Primary Angioplasty
A Phase 2 study testing inhaled nitric oxide in people with STEMI, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
Trial summary
Reperfusion of ischemic myocardium, termed ischemia/reperfusion during the treatment of MI may result in paradoxical myocardial injury compromising myocardial salvage and left ventricular functional recovery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- STEMI
- What is being tested?
- inhaled nitric oxide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteIsrael
- Study dates
- Aug 2009to Aug 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is over 18 years old
- Subject has an acute ST segment elevation myocardial infarction defined as the presence of ST segment elevation in at least two contiguous leads or new left bundle branch block and the presence of symptoms at rest typical of myocardial ischemia for at least 30 minutes but less than 12 hours prior to admission
- Subject is eligible for primary PCI
- Subject understands the nature of the procedure and provides written informed consent prior to the catheterization procedure
- Subject is willing to comply with pre specified follow up evaluation and can be contacted by telephone
- Subject is male or a non pregnant female
- Subject is a candidate for urgent PCIintervention for reperfusion of an infarct related artery that is totally occluded and is more than 2.5mm in diameter.
Who cannot join
- Subject is currently enrolled in another investigational study of a new drug, biologic or device at the time of study screening
- Ischemic symptom onset more than 12 hours prior to presentation
- Subject with a history of a previous Q wave myocardial infarction
- A PCI procedure of any kind within 30 days prior to the procedure.
- Subject with previously known impaired left ventricular function from any reason
- Subject with STEMI that requires treatment of the left main coronary artery during the primary PCI.
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- Patients who are hemodynamically unstable (Killip class 3 or 4, mechanical ventilation, life threatening ventricular arrhythmias, patients resuscitated from cardiac arrest)
- Co-morbid condition that could limit the subject's ability to participate in the trial or to comply with follow-up requirements
- Concurrent medical condition with a life expectancy of less than 12 months.
- Documented left ventricular ejection fraction less than 45% prior to the index event
- History of cerebrovascular accident or transient ischemic attack in the last 6 months
- Known severe renal failure (serum creatinine level more than2.5 mg/dl
- History of bleeding diathesis or coagulopathy or inability or unwillingness to receive blood transfusions.
- Known hypersensitivity or contraindication to aspirin, heparin or bivalirudin, clopidogrel and ticlopidine, cobalt, nickel, L 605 Cobalt chromium alloy, or sensitivity to contrast media, which cannot be adequately pre-medicated
- Bleeding diathesis.
- Evidence of active gastrointestinal bleeding or a history of such bleeding that is not known to have been treated and proven to have resolved
- History of hepatitis (viral, ischemic or chemically induced), clinical jaundice, history of cirrhosis
- Subject is deemed in definite need of CABG surgery during the index hospitalization
- Recent (less than 72 hours) use of sildenafil (Viagra, Revatio), verdenafil (Lefvitra), or tadalfil (Cialis)
- Angiographic exclusion criteria:
- The infarct vessel is a surgical bypass graft, clinically significant left main coronary artery disease (obstruction greater than 50 percent in the left main coronary artery) in the absence of patent bypass grafts to the left anterior descending and left circumflex arteries;
- Target lesion is located in an aorto-ostial position or within 2 mm of the origin of the left anterior descending (LAD) or left circumflex (LCX)
- target lesion(s) with severe calcification.
Trial locations and contacts
1 site in 1 country.
About this study
Reperfusion of ischemic myocardium, termed ischemia/reperfusion during the treatment of MI may result in paradoxical myocardial injury compromising myocardial salvage and left ventricular functional recovery. Nitric oxide (NO) modulates many of the processes contributing to ischemia-reperfusion injury (IR)and inhaled NO (iNO) has been shown to decease infarct size in animal models of IR. iNO has been studied in various clinical settings and has shown promise im modulating the detrimental effects of IR. Clinical toxicity potentially associated with the use of iNO was of no apparent concern in these studies. Although controlled trials of iNO therapy in humans with acute MI have not been published, anecdotal experience indicates a beneficial impact of iNO on the hemodynamic course of patients with right ventricular MI. iNO is widely used to treat neonatal hypoxemia and acute pulmonary hypertension. iNO has been studied at this dose in various clinical settings and side effects related to its use at such doses are extremely uncommon. The effect of iNO on IR injury in patients with acute ST-segment elevation MI is unknown. The investigator intend to perform a prospective, randomized, placebo-controlled, clinical trial of iNO in patients with acute MI undergoing primary percutaneous intervention to determine whether this form of therapy can decrease infarct size and improve clinical outcomes.
Read the detailed description
Eligible consenting patients will be randomly assigned to either of the 2 treatment arms using a computer-generated randomization sequence. Treatment arms: 1) Intervention group, treated with inhalation of a mixture of NO 80 ppm and oxygen; or, 2) Control group, inhalation oxygen and nitrogen (placebo). In both groups, oxygen will be administered at the minimal FiO2 required to maintain arterial oxygen saturation determined by pulse oxymetry >97%. Inhalation treatment will be given throughout the angioplasty procedure via a reservoir face mask and a dedicated respiratory circuit. Nitric oxide will be delivered using an FDA-approved device marketed in Israel under license by the Ministry of Health. The device is in routine clinical use in intensive care units, neonatal care units, and catheterization laboratories. An NO-level detector will be employed in the catheterization laboratory to monitor the ambient NO exposure of the staff.
Upon arrival in the catheterization laboratory, a 40 ml blood sample will be obtained for a full chemistry panel, lipid levels, complete blood count. Creatine kinase, creatine kinase MB fraction, and troponin I will be measured at baseline and every 4 hours following the angioplasty procedure during the first 24 hours, and then every 6 hours during the second and third days, and as clinically indicated thereafter.Methemoglobin levels will be measured at baseline, every 30 minutes throughout the interventional procedure, at procedure completion, and at 4 hours post procedure.
All patients will undergo diagnostic angiography and interventional procedures as per standard clinical practice. Post procedural pharmacotherapy, sheath removal, and deployment of hemostatic devices will be left to the discretion of the attending physicians.
Following treatment in the catheterization laboratory, medical treatment throughout hospitalization and recommendations for therapy after discharge will be left to the discretion of the attending cardiologists managing patient care on the hospital wards. These cardiologists will be blinded to the patient randomization status.
- Conditions
- STEMI
- Being tested
- inhaled nitric oxide
- Keywords
- ST elevated Myocardical infraction
- Medical subject headings
- ST Elevation Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inhaled nitric oxideProcedure or surgery
Also called iNO
80 PPM
| Study group | Role | What they receive |
|---|---|---|
| nitric oxide | Experimental | inhaled nitric oxide 80 ppm and oxygen Receives: Procedure: inhaled nitric oxide |
| standart of care | Placebo comparator | no intervention Receives: Procedure: inhaled nitric oxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infarct size assessed by measurements of myocardial biomarkers (creatine kinase [CK], CK MB, troponin I) from blood samples obtained at admission and repeatedly over the next 3 days.
Measured: 3-days post randomization
Secondary outcomes (1)
Major Adverse Cardiac Events (MACE), defined as death, myocardial infarction (MI, Q wave and non-Q wave), emergent bypass surgery, or clinically driven target lesion(s) revascularization (TLR) (repeat PCI or CABG) at 12-months.
Measured: 12-month post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2009 (estimated)
- Study startAug 2009
- Primary completionOct 2011
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for STEMIStudies of the same condition, open and under way.
- More trials run by Tel-Aviv Sourasky Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tel-Aviv Sourasky Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, michal roll, Tel-Aviv Sourasky Medical Center
- Investigators
- Amir S Halkin, MD, Principal investigator, TASMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00854711
- Sponsor's protocol ID
- TASMC-09-AH-7009-CTIL
- Acronym
- ENAMOR
- Status last verified
- Jul 2016
- First submitted
- 16 Feb 2009
- Last updated
- 7 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Placebo-controlled Trial of Inhaled iNO in Acute ST-segment Elevation MI Treated by Primary Angioplasty
- ClinicalTrials.gov ID
- NCT00854711
- Acronym / sponsor ID
- ENAMOR / TASMC-09-AH-7009-CTIL
- Conditions
- STEMI
- Keywords
- ST elevated Myocardical infraction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Tel-Aviv Sourasky Medical CenterOther government
- Study start
- Aug 2009
- Primary completion
- Oct 2011 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 3 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Reperfusion of ischemic myocardium, termed ischemia/reperfusion during the treatment of MI may result in paradoxical myocardial injury compromising myocardial salvage and left ventricular functional recovery. Nitric oxide (NO) modulates many of the processes contributing to ischemia-reperfusion injury (IR)and inhaled NO (iNO) has been shown to decease infarct size in animal models of IR. iNO has been studied in various clinical settings and has shown promise im modulating the detrimental effects of IR. Clinical toxicity potentially associated with the use of iNO was of no apparent concern in these studies. Although controlled trials of iNO therapy in humans with acute MI have not been published, anecdotal experience indicates a beneficial impact of iNO on the hemodynamic course of patients with right ventricular MI. iNO is widely used to treat neonatal hypoxemia and acute pulmonary hypertension. iNO has been studied at this dose in various clinical settings and side effects related to its use at such doses are extremely uncommon. The effect of iNO on IR injury in patients with acute ST-segment elevation MI is unknown. The investigator intend to perform a prospective, randomized, placebo-controlled, clinical trial of iNO in patients with acute MI undergoing primary percutaneous intervention to determine whether this form of therapy can decrease infarct size and improve clinical outcomes.
Detailed description
Eligible consenting patients will be randomly assigned to either of the 2 treatment arms using a computer-generated randomization sequence. Treatment arms: 1) Intervention group, treated with inhalation of a mixture of NO 80 ppm and oxygen; or, 2) Control group, inhalation oxygen and nitrogen (placebo). In both groups, oxygen will be administered at the minimal FiO2 required to maintain arterial oxygen saturation determined by pulse oxymetry >97%. Inhalation treatment will be given throughout the angioplasty procedure via a reservoir face mask and a dedicated respiratory circuit. Nitric oxide will be delivered using an FDA-approved device marketed in Israel under license by the Ministry of Health. The device is in routine clinical use in intensive care units, neonatal care units, and catheterization laboratories. An NO-level detector will be employed in the catheterization laboratory to monitor the ambient NO exposure of the staff.
Upon arrival in the catheterization laboratory, a 40 ml blood sample will be obtained for a full chemistry panel, lipid levels, complete blood count. Creatine kinase, creatine kinase MB fraction, and troponin I will be measured at baseline and every 4 hours following the angioplasty procedure during the first 24 hours, and then every 6 hours during the second and third days, and as clinically indicated thereafter.Methemoglobin levels will be measured at baseline, every 30 minutes throughout the interventional procedure, at procedure completion, and at 4 hours post procedure.
All patients will undergo diagnostic angiography and interventional procedures as per standard clinical practice. Post procedural pharmacotherapy, sheath removal, and deployment of hemostatic devices will be left to the discretion of the attending physicians.
Following treatment in the catheterization laboratory, medical treatment throughout hospitalization and recommendations for therapy after discharge will be left to the discretion of the attending cardiologists managing patient care on the hospital wards. These cardiologists will be blinded to the patient randomization status.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| nitric oxide | Experimental | Procedure: inhaled nitric oxideinhaled nitric oxide 80 ppm and oxygen |
| standart of care | Placebo comparator | Procedure: inhaled nitric oxideno intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subject is over 18 years old
- Subject has an acute ST segment elevation myocardial infarction defined as the presence of ST segment elevation in at least two contiguous leads or new left bundle branch block and the presence of symptoms at rest typical of myocardial ischemia for at least 30 minutes but less than 12 hours prior to admission
- Subject is eligible for primary PCI
- Subject understands the nature of the procedure and provides written informed consent prior to the catheterization procedure
- Subject is willing to comply with pre specified follow up evaluation and can be contacted by telephone
Key exclusion criteria (23 listed)
- Subject is currently enrolled in another investigational study of a new drug, biologic or device at the time of study screening
- Ischemic symptom onset more than 12 hours prior to presentation
- Subject with a history of a previous Q wave myocardial infarction
- A PCI procedure of any kind within 30 days prior to the procedure.
- Subject with previously known impaired left ventricular function from any reason
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inhaled nitric oxideAlso: iNO80 PPM | Procedure or surgery | nitric oxide, standart of care |
Primary outcome
Infarct size assessed by measurements of myocardial biomarkers (creatine kinase [CK], CK MB, troponin I) from blood samples obtained at admission and repeatedly over the next 3 days.
Time frame: 3-days post randomization
1 secondary outcome
Major Adverse Cardiac Events (MACE), defined as death, myocardial infarction (MI, Q wave and non-Q wave), emergent bypass surgery, or clinically driven target lesion(s) revascularization (TLR) (repeat PCI or CABG) at 12-months.
Time frame: 12-month post randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amir S Halkin, MD principal investigator
TASMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing inhaled nitric oxide in people with STEMI, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infarct size assessed by measurements of myocardial biomarkers (creatine kinase [CK], CK MB, troponin I) from blood samples obtained at admission and repeatedly over the next 3 days. (time frame: 3-days post randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2016.