ALBATROSS: Aldosterone Blockade Early After Acute Myocardial Infarction

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT01059136

Collaborator

(none)

1,603

Enrollment

Location

Arms

53.9

Duration (Months)

29.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study hypothesis : An early blockade of aldosterone receptors initiated at the first medical contact after acute myocardial infarction may reduce major cardiovascular events within 6 months after the occurrence of the myocardial infarction.

Primary efficacy criterion : The 6 month rate of the composite of death, resuscitated cardiac arrest, potentially lethal ventricular arrhythmia, indication for implantation of an implantable cardioversion device, occurrence or aggravation of heart failure.

Primary objective: To demonstrate the superiority of aldosterone blockade initiated as soon as possible within 72 hours after the onset of acute myocardial infarction on top of standard therapy, compared to standard therapy alone, with or without reperfusion therapy.

Study design : Prospective, multi-centre randomised, open labeled with 2 parallel study arms.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Drug: Spironolactone	Phase 3

Detailed Description

Rational :The blockade of the renin-angiotensin-aldosterone (RAA) pathway by angiotensin conversion enzyme inhibitors (ACEI) is one corner stone in the management of heart failure as well as the management of ischemic heart disease, especially after acute myocardial infarctionHigh plasma aldosterone levels have been associated with both direct and indirect toxic effects on myocardium. ACEIs are associated with partial and temporary reduction of plasma aldosterone levels.The RALES randomized controlled trial has shown a reduction of mortality associated with the use of the selective aldosterone receptor blocker spironolactone, on top of standard therapy including ACEIs in the setting of NYHA 3-4 chronic heart failure. The EPHESUS randomized controlled trial has shown a reduction of mortality associated with the use of another selective aldosterone receptor blocker Eplerenone, initiated 3 to 14 days after acute myocardial infarction complicated by clinical heart failure and left ventricular ejection fraction < 40%.Both previous studies have also reported a rapid reduction of global and arrhythmia-related mortality, within 30 days after the initiation of the medication.Such benefit has been reported after delayed initiation of aldosterone blocked, while aldosterone is at its highest level at presentation after acute myocardial infarction, with a rapid decrease within days after admission. Furthermore high aldosterone levels on admission are associated with adverse outcome independent of heart failure.

The ALBATROSS trial :Hypothesis: An early blockade of aldosterone receptors initiated at the first medical contact after acute myocardial infarction may reduce major cardiovascular events within 6 months after the occurrence of the myocardial infarction.

Study Design

Study Type:

Interventional

Actual Enrollment :

1603 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Aldosterone Lethal Effects Blocked in AMI Treated With or Without Reperfusion to Improve Outcome and Survival at Six Months Follow-up: THE ALBATROSS TRIAL

Study Start Date :

Feb 1, 2010

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1:Spironolactone Aldosterone blockade on top of standard therapy	Drug: Spironolactone Unique 200mg IV dose of Potassium Canrenoate followed by 25 mg daily oral dose of Spironolactone for 6 months
No Intervention: 2:Standard therapy Standard therapy

Arm

Intervention/Treatment

Experimental: 1:Spironolactone

Aldosterone blockade on top of standard therapy

Drug: Spironolactone

Unique 200mg IV dose of Potassium Canrenoate followed by 25 mg daily oral dose of Spironolactone for 6 months

No Intervention: 2:Standard therapy

Standard therapy

Outcome Measures

Primary Outcome Measures

The 6 month rate of the composite of death, resuscitated cardiac arrest, potentially lethal ventricular arrhythmia, indication for implantable cardioversion device, occurrence or aggravation of heart failure. [6 months]

Secondary Outcome Measures

Any of the criteria of the primary endpoint [6 months]
primary endpoint+ myocardial infarction+stroke cardiovascular death [6 months]
death + resuscitated cardiac arrest [6 months]
Death+resuscitated cardiac arrest+ventricular arrhythmia+indication for implantable defibrillator device [6 months]
death+heart failure [6 months]
Acute renal failure [6 months]
primary endpoint [hospital discharge and 30 days]
rate of hyperkaliemia (> 5.5 mmol.l-1) [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 ans
Ischemic symptom of ≥ 20 minutes
Randomization within 72 hours after symptom onset
Electrocardiogram or biological evidence of myocardial infarction:

ST segment elevation ≥ 2 mm in ≥ 2 adjacent precordial derivations
ST segment elevation ≥ 1 mm in ≥ 2 adjacent peripheral derivations
New left bundle branch block
New significant Q wave in ≥ 2 adjacent peripheral derivations
Troponin levels ≥3 times upper local limit of normal values and Thrombolysis In Myocardial Infarction (TIMI) non-ST elevation myocardial infarction risk score ≥

Patients with health insurance
Written informed consent obtained from:
- the patient
-A member of the family or the person of confidence if the patient is unable to provide informed consent

Exclusion Criteria:

Contraindication or known intolerance to study drugs
Patients already treated by aldosterone blockers for diseases other than systemic hypertension (e.g. primary hyperaldosteronism)
Hyperkaliemia >5.5 mmol/l at the time of randomization
Renal function impairment :Plasma creatinin level > 220 µmol/l and/or Creatinin clearance 30 ml/min
Severe liver deficiency (Child-Pugh Class 3)
Pregnant or breast feeding women, or women desiring pregnancy within 6 months after randomization
Patients already included in another biomedical intervention trial
Life expectancy < 1 year
Cardiac arrest lasting (ECM) >10 minutes prior to randomization
Patient unable or unwilling to comply with the treatment or the follow-up visits