NCT01882179

Brief 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. 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
61

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Nov 2013

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 17, 2013

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 20, 2013

Completed
4 months until next milestone

Study Start

First participant enrolled

November 1, 2013

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2016

Completed
Last Updated

October 26, 2016

Status Verified

May 1, 2016

Enrollment Period

2.5 years

First QC Date

June 17, 2013

Last Update Submit

October 25, 2016

Conditions

ST-elevation Myocardial Infarction

Keywords

Reperfusion injurymyocardial infarct sizeMRIspironolactone

Outcome Measures

Primary Outcomes (1)

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

    12 weeks after STEMI

Secondary Outcomes (6)

  • Markers of myocardial reperfusion injury

    48 hours

  • Microvascular obstruction on cardiac MRI

    1-3 days after STEMI

  • Myocardial salvage

    12 weeks

  • Acute myocardial infarct size

    1-3 days

  • LV remodelling

    12 week cardiac MRI scan

  • +1 more secondary outcomes

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Intravenous saline bolus prior to PPCI followed by oral placebo for 3 months

Drug: placebo

Mineralocorticoid receptor antagonist

ACTIVE COMPARATOR

1st 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.

Drug: Mineralocorticoid receptor antagonist potassium-canrenoate

Interventions

Mineralocorticoid receptor antagonist potassium-canrenoateDRUG
Mineralocorticoid receptor antagonist
placeboDRUG
Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • Angiographically proven proximal occlusion (TIMI 0) of a major coronary vessel (LAD, LCX, RCA).
  • Normal potassium (\<5.0 mmol/l)

You may not qualify if:

  • 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
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Cardiothoracic Center - Basildon and Thurrock University Hospitals

Basildon, Essex, SS16 5NL, United Kingdom

Location

London Chest Hospital

London, London, E2 9JX, United Kingdom

Location

Heart Hospital London

London, London, W1G 8PH, United Kingdom

Location

Leeds Genereal Infirmary

Leeds, United Kingdom

Location

Related Publications (4)

  • 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.

    PMID: 12668699BACKGROUND

  • 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.

    PMID: 21073363BACKGROUND

  • 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.

    PMID: 10471456BACKGROUND

  • 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.

    PMID: 20028693BACKGROUND

MeSH Terms

Conditions

ST Elevation Myocardial InfarctionReperfusion Injury

Condition Hierarchy (Ancestors)

Myocardial InfarctionMyocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosisPostoperative Complications

Study Officials

  • Derek J Hausenloy, PhD

    University College London, Hatter Cardiovascular Institute

    STUDY DIRECTOR

  • Georg M Fröhlich, MD

    University College London, The Heart Hospital

    STUDY CHAIR

  • Pascal Meier, MD

    University College London, The Heart Hospital

    PRINCIPAL INVESTIGATOR

  • Reto Gamma, MD

    Basildon and Thurrock University Hospitals

    PRINCIPAL INVESTIGATOR

  • Anthony Mathur, PhD

    London Chest Hospital

    PRINCIPAL INVESTIGATOR

  • John Greenwood, MD

    Leeds General Infirmary

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 17, 2013

First Posted

June 20, 2013

Study Start

November 1, 2013

Primary Completion

May 1, 2016

Study Completion

May 1, 2016

Last Updated

October 26, 2016

Record last verified: 2016-05

Locations

GB(4)