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Myocardial InfarctionPhase 2NITRITE-AMINCT01584453

Safety and Effectiveness of Intra-coronary Nitrite in Acute Myocardial Infarction

A Phase 2 study testing Sodium Nitrite in people with Myocardial Infarction and Reperfusion Injury, run by Barts & The London NHS Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Despite advances in the treatment of heart attacks the complications and death rates from failure of the heart to pump properly after treatment remain high. A heart attack occurs when one or more of the arteries that supply blood to the heart become blocked, causing the heart to be starved of oxygen and nutrients. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Sodium Nitrite
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
80 participants
Where
1 siteUnited Kingdom
Study dates
Apr 2012to Jan 2016
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients aged at least 18 years
  • Acute STEMI with ECG showing ST-segment elevation of 1mm or more in two adjacent limb leads or 2mm or more in at least two contiguous precordial leads or new left bundle branch block;
  • Haemodynamically stable
  • Estimated symptom to balloon or aspiration time < 6 hours
  • Angiographically i) PPCI indicated for revascularisation ii) Single epicardial artery to be treated iii) Expected ability to use over the wire balloon

Who cannot join

  • Patients on organic nitrate treatment (Nicorandil, isosorbide mononitrate)
  • Previous history of AMI, systolic dysfunction or CABG
  • Subjects presenting with cardiogenic shock (systolic blood pressure <80 mmHg for > 30 minutes, or requiring inotropes/emergency intra aortic balloon pump or cardiopulmonary resuscitation
  • Current diagnosis of or treatment for malignancy, other than non-melanoma skin cancer.
  • Current life-threatening condition other than vascular disease that may prevent a subject completing the study.
  • Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication.
Show all 13Show fewer
  • Patients considered unsuitable to participate by the research team (e.g., due to medical reasons, laboratory abnormalities, or subject's unwillingness to comply with all study-related procedures).
  • Severe acute infection, or significant trauma (burns, fractures).
  • Pregnancy.
  • Contra-indications to CMR scanning i) Pacemakers, intracranial clips or other metal implants ii) Claustrophobia iii) Renal failure (eGFR < 30mls/min)
  • History of alcohol or drug abuse within the past 6 months.
  • History of congenital methaemoglobinaemia.
  • Angiographically severe vessel tortuosity, diffuse disease or severe calcification which may impede successful delivery of the the over the wire balloon.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • London Chest Hospital

    Bethnal Green, London, E2 9JX

Other trials in United Kingdom

About this study

Official title: A Randomised, Double-blind, Placebo-controlled Trial Assessing the Safety and Efficacy of Intracoronary Nitrite Infusion During Acute Myocardial Infarction

Despite advances in the treatment of heart attacks the complications and death rates from failure of the heart to pump properly after treatment remain high. A heart attack occurs when one or more of the arteries that supply blood to the heart become blocked, causing the heart to be starved of oxygen and nutrients. This results in damage to the heart and so the the heart pumps less well. The main treatment for a heart attack is balloon treatment to open the blocked artery (called primary angioplasty). Whilst re-opening the artery is essential and allows blood to flow to the area of the heart starved of oxygen, this process also causes damage itself (called reperfusion injury) and increases the size of the heart attack further. Currently there are no treatments available that reduce this reperfusion injury. The investigators and others have shown that a substance called sodium nitrite reduces reperfusion injury in experimental models of a heart attack. The aim of this research is to perform a trial to investigate whether during a heart attack, an infusion of sodium nitrite into the damaged artery protects against reperfusion injury and reduces heart attack size in patients.

Read the detailed description

Coronary heart disease is still the commonest cause of death in the UK (in the main as a consequence of acute myocardial infarction (AMI)). Presently, timely and effective reperfusion with primary percutaneous coronary intervention (PPCI) remains the most effective treatment strategy for limiting infarct size, preserving left ventricular ejection fraction (LVEF), and improving the clinical outcomes in such patients. However, substantial mortality and morbidity rates still persist with respect to longer term outcome. One of the main determinants of prognosis after AMI is the size of the infarct. Thus, identification of additional strategies that might decrease infarct size is desirable.

Evidence from pre-clinical studies suggests that inorganic nitrite administration reduces infarct size in animal models of AMI. In this study we aim to translate these findings into man. We will test the hypothesis that in patients with STEMI undergoing PPCI, an intra-coronary injection of nitrite, initiated prior to establishment of full reperfusion reduces infarct size through prevention of ischemia-reperfusion injury.

Being tested
Sodium Nitrite, Sodium Chloride Placebo
Medical subject headings
Myocardial Infarction, Reperfusion Injury, Myocardial Ischemia, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sodium NitriteDrug

    A bolus of sodium nitrite solution (1.8 micromol in 10 ml PRe-diluted in 0.9% sodium chloride in a syringe) will be delivered over 30-60 seconds via intracoronary injection initiated during the re-establishment of antegrade epicardial flow with PPCI.

  • Sodium Chloride PlaceboDrug

    The control intervention is a bolus of 0.9% sodium chloride solution (prepared with an identical appearance to the sodium nitrite).

Study groups in NCT01584453
Study groupRoleWhat they receive
Sodium NitriteExperimentalNot described
Receives: Drug: Sodium Nitrite
PlaceboPlacebo comparatorNot described
Receives: Drug: Sodium Chloride Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Infarct size measured by CK area under the curve

    AUC measured over the 1st 48 hours after PPCI (0,4,8,12,18,24,36 and 48 hours)

    Measured: 1st 48 hours after AMI

Secondary outcomes (9)

  1. Infarct size measured by Troponin T Area under the curve

    AUC measured over the 1st 48 hours after PPCI (0,4,8,12,18,24,36 and 48 hours)

    Measured: 1st 48 hours post AMI

  2. Infarct size, assessed by CMR at 6 months ± 2 weeks.

    Infarct size, assessed by CMR at 6 months ± 2 weeks.

    Measured: 6 months ± 2 weeks.

  3. Infarct size as a proportion of area at risk measured at 48 hours by CMR.

    Infarct size as a proportion of area at risk measured at 48 hours by CMR.

    Measured: 48 hours

  4. The acute safety and tolerability of intra-coronary nitrite in STEMI

    Safety profile of IC nitrate (death, MI, CVA, arrhythmia, hypotension, methaemoglobinaemia)

    Measured: 1st 48 hours

  5. Assessment of MACE endpoints at 6 and 12 months (death, heart failure, myocardial infarction, stroke, need for repeat revascularisation)

    Measured: 12 months

  6. Markers of inflammation measured at baseline, 30 minutes, 4 and 24 hours post PCI

    hs-CRP, MCP-1

    Measured: 24 hours

  7. Assessment of platelet reactivity at baseline, 30 minutes, 4 and 24 hours post PCI

    ADP, collagen, PBS

    Measured: 24 hours

  8. Plasma nitrite and cyclic guanosine monophosphatase (cGMP) concentrations measured at baseline, post procedure, at 4 hours and 24 hours post-PCI

    Measured: 24 hours

  9. Cost-utility of Nitrite over at 3 years

    ICER based on outcome and QoL (EQ5D)

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2012 (estimated)
  2. Study startApr 2012
  3. Primary completionNov 2013
  4. Study completionJan 2016

Resources

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
Single group
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01584453
Sponsor's protocol ID
11/LO/1500
Acronym
NITRITE-AMI
Status last verified
Jul 2015
First submitted
23 Apr 2012
Last updated
29 Nov 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Jones DA, Khambata RS, Andiapen M, Rathod KS, Mathur A, Ahluwalia A. Intracoronary nitrite suppresses the inflammatory response following primary percutaneous coronary intervention. Heart. 2017 Apr;103(7):508-516. doi: 10.1136/heartjnl-2016-309748. Epub 2016 Sep 28.

    PubMed 27683405

  • Jones DA, Pellaton C, Velmurugan S, Rathod KS, Andiapen M, Antoniou S, van Eijl S, Webb AJ, Westwood MA, Parmar MK, Mathur A, Ahluwalia A. Randomized phase 2 trial of intracoronary nitrite during acute myocardial infarction. Circ Res. 2015 Jan 30;116(3):437-47. doi: 10.1161/CIRCRESAHA.116.305082. Epub 2014 Dec 15.

    PubMed 25512434

  • Jones DA, Andiapen M, Van-Eijl TJ, Webb AJ, Antoniou S, Schilling RJ, Ahluwalia A, Mathur A. The safety and efficacy of intracoronary nitrite infusion during acute myocardial infarction (NITRITE-AMI): study protocol of a randomised controlled trial. BMJ Open. 2013 Apr 2;3(4):e002813. doi: 10.1136/bmjopen-2013-002813. Print 2013.

    PubMed 23550096

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sodium Nitrite in people with Myocardial Infarction and Reperfusion Injury, run by Barts & The London NHS Trust at 1 site in United Kingdom.

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 5 inclusion and 13 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 29 Nov 2017. 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 United Kingdom. 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 measured by CK area under the curve (time frame: 1st 48 hours after AMI). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01584453, which also lists 3 linked publications.

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 29 Nov 2017.

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