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ST-elevation Myocardial InfarctionPhase 3MINIMISE-STEMINCT01882179

Early Mineralocorticoid Receptor Antagonist Treatment to Reduce Myocardial Infarct Size

A Phase 3 study testing Mineralocorticoid receptor antagonist potassium-canrenoate in people with ST-elevation Myocardial Infarction, run by University College, London at 4 sites 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

Heart attacks, or myocardial infarcts, are a major cause of death and disability in the UK. Immediate unblocking of the obstructed heart vessel with a balloon catheter and implantation of a mesh scaffold (stent) in heart centers is warranted in these patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
ST-elevation Myocardial Infarction
What is being tested?
Mineralocorticoid receptor antagonist potassium-canrenoate
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
61 participants
Where
4 sitesUnited Kingdom
Study dates
Nov 2013to May 2016
Phase
Phase 3
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

  • Patients >18 years
  • Patients presenting with acute STEMI (as assessed by 12 lead ECG; ST segment elevation ≥2 mm (0.2 mV) in 2 or more contiguous precordial leads or ≥1mm (0.1mm) in 2 or more adjacent limb leads).
  • Presentation within 12 hours after symptom onset
  • Inclusion criteria for randomization (assessed in catheter laboratory)
  • Angiographically proven proximal occlusion (TIMI 0) of a major coronary vessel (LAD, LCX, RCA).
  • Normal potassium (<5.0 mmol/l)

Who cannot join

  • Patients with known LVEF ≤40%
  • Participation in another trial
  • Cardiogenic shock (positive shock index OR need for catecholamine support OR systolic blood pressure < 90 mmHg)
  • Killip class > 2
  • Prior myocardial infarction
  • Known compromised renal function (eGFR < 30 ml/min/1.73 m2) or potassium > 5.0 mmol/l
Show all 10Show fewer
  • Current treatment with mineralocorticoid receptor antagonists
  • Pregnant or lactating females
  • Allergies to IMP or its excipients
  • Known contraindication to cardiac magnetic resonance imaging (MRI) such as significant claustrophobia, severe allergy to gadolinium chelate contrast, , presence of MRI contraindicated implanted devices (eg, pacemaker, implanted cardiac defibrillator, cardiac resynchronization therapy device, cochlear implant), imbedded metal objects (eg, shrapnel), or any other contraindication for cardiac MRI.

Trial locations and contacts

4 sites in 1 country.

United Kingdom4 sites

  • Cardiothoracic Center - Basildon and Thurrock University Hospitals

    Basildon, Essex, SS16 5NL

  • Leeds Genereal Infirmary

    Leeds

  • London Chest Hospital

    London, London, E2 9JX

  • Heart Hospital London

    London, London, W1G 8PH

Other trials in United Kingdom

About this study

Official title: MINeralocorticoid Receptor Antagonist Pretreatment to MINIMISE Reperfusion Injury After ST-Elevation Myocardial Infarction (STEMI)

Heart attacks, or myocardial infarcts, are a major cause of death and disability in the UK. Immediate unblocking of the obstructed heart vessel with a balloon catheter and implantation of a mesh scaffold (stent) in heart centers is warranted in these patients. Morbidity and mortality in this patient group is related to the infarct size. Therefore, there is a need to discover novel therapeutic agents which reduce myocardial infarct size and preserve the contractile heart function.

Large trials involving several thousand patients have demonstrated a survival benefit in patients with impaired heart function due to a heart attack, who received a mineralo-corticoid receptor antagonist (MRA, drug name: spironolactone). In these trials patients received the drug late, 3-14 days after the heart attack.

Read more

Our proposal is to investigate whether MRA therapy administered intravenously prior to unblocking an occluded heart vessel, can reduce infarct size and as such can prevent long term sequelae of heart attacks.

150 patients admitted to 4 tertiary care hospitals (Heart Hospital London, London Chest, Essex Cardiothoracic Center and Leeds General Infirmary) for heart attack will be randomly assigned to receive MRA treatment or placebo. The first dose of the MRA will be applied intravenously immediately in the catheter suite, even before re-opening of the occluded vessel. From the second day on, patients will be prescribed oral MRA treatment, as a pill, for a total of three months. Before hospital discharge and after three months, a magnetic resonance image (MRI) of the heart will accurately investigate the evolution of infarct (scar) size and the contractile heart function and compare the group of patients who received the MRA drug versus the placebo control group. Of note, patients with an ejection fraction <40% AND signs of heart failure OR diabetes will go on open label eplerenone according to current guidelines, instead of the study drug.

This study will give first evidence, if very early MRA treatment improves heart function and should be used as early as possible for treatment of patients after a heart attack.

Being tested
Mineralocorticoid receptor antagonist potassium-canrenoate, placebo
Keywords
Reperfusion injury, myocardial infarct size, MRI, spironolactone
Medical subject headings
ST Elevation Myocardial Infarction, Reperfusion Injury

What participants receive

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

  • Mineralocorticoid receptor antagonist potassium-canrenoateDrug

  • placeboDrug

Study groups in NCT01882179
Study groupRoleWhat they receive
PlaceboPlacebo comparatorIntravenous saline bolus prior to PPCI followed by oral placebo for 3 months
Receives: Drug: placebo
Mineralocorticoid receptor antagonistActive comparator1st dose (day 0) given i.v. (potassium-canrenoate), before primary PCI day 1 - 12 weeks: spironolactone 25mg daily, which is uptitrated to 50mg daily after 2 weeks, if possible In case the LVEF <40% on baseline MRI and the patient shows signs of heart failure or is diabetic, the patient will receive open label eplerenone instead of the study drug, according to current guidelines.
Receives: Drug: Mineralocorticoid receptor antagonist potassium-canrenoate

What is being measured

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

  1. Myocardial infarct (MI) size, as assessed by cardiac magnetic resonance imaging

    Measured: 12 weeks after STEMI

Secondary outcomes (6)

  1. Markers of myocardial reperfusion injury

    TIMI flow post-PPCI, ST-segment resolution post-PPCI

    Measured: 48 hours

  2. Microvascular obstruction on cardiac MRI

    hypodense area of late gadolinium enhancement

    Measured: 1-3 days after STEMI

  3. Myocardial salvage

    Area at risk assessed by T2 weighted imaging subtract final MI size

    Measured: 12 weeks

  4. Acute myocardial infarct size

    serum biomarkers: hsTnT, CK-MB, CK and cardiac MRI: late gadolinium enhancement

    Measured: 1-3 days

  5. LV remodelling

    LV end-diastolic and end-systolic volumes, LV ejection fraction, LV mass and wall-thickness

    Measured: 12 week cardiac MRI scan

  6. Clinical outcome measures

    cardiovascular death, non-fatal myocardial infarction, revascularisation, hospitalisation for heart failure, hyperkalemia, deterioration of kidney function, need for dialysis

    Measured: 12 weeks

Timeline

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

  1. First posted20 Jun 2013 (estimated)
  2. Study startNov 2013
  3. Primary completionMay 2016
  4. Study completionMay 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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01882179
Sponsor's protocol ID
12/0533
Acronym
MINIMISE-STEMI
Status last verified
May 2016
First submitted
17 Jun 2013
Last updated
26 Oct 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 Apr 3;348(14):1309-21. doi: 10.1056/NEJMoa030207. Epub 2003 Mar 31.

    PubMed 12668699

  • Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B; EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011 Jan 6;364(1):11-21. doi: 10.1056/NEJMoa1009492. Epub 2010 Nov 14.

    PubMed 21073363

  • Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2;341(10):709-17. doi: 10.1056/NEJM199909023411001.

    PubMed 10471456

  • Schmidt K, Tissier R, Ghaleh B, Drogies T, Felix SB, Krieg T. Cardioprotective effects of mineralocorticoid receptor antagonists at reperfusion. Eur Heart J. 2010 Jul;31(13):1655-62. doi: 10.1093/eurheartj/ehp555. Epub 2009 Dec 21.

    PubMed 20028693

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Mineralocorticoid receptor antagonist potassium-canrenoate in people with ST-elevation Myocardial Infarction, run by University College, London at 4 sites 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 6 inclusion and 10 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 26 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Myocardial infarct (MI) size, as assessed by cardiac magnetic resonance imaging (time frame: 12 weeks after STEMI). 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 NCT01882179, which also lists 4 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 26 Oct 2016.

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