Clinical trial NCT01059136: Aldosterone Blockade Early After Acute Myocardial Infarction
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myocardial Infarction
Keywords: Myocardial infarction
Outcome
Aldosterone
Spironolactone
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2010-01-29
Enrollment: 1603
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 ans
2. Ischemic symptom of ≥ 20 minutes
3. Randomization within 72 hours after symptom onset
4. 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 ≥ 3.
5. Patients with health insurance
6. Written informed consent obtained from:

   1. - the patient
   2. -A member of the family or the person of confidence if the patient is unable to provide informed consent

Exclusion Criteria:

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

Primary outcomes:
measure: 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.
timeFrame: 6 months
Secondary outcomes:
measure: Any of the criteria of the primary endpoint
timeFrame: 6 months
measure: primary endpoint+ myocardial infarction+stroke cardiovascular death
timeFrame: 6 months
measure: death + resuscitated cardiac arrest
timeFrame: 6 months
measure: Death+resuscitated cardiac arrest+ventricular arrhythmia+indication for implantable defibrillator device
timeFrame: 6 months
measure: death+heart failure
timeFrame: 6 months
measure: Acute renal failure
timeFrame: 6 months
measure: primary endpoint
timeFrame: hospital discharge and 30 days
measure: rate of hyperkaliemia (> 5.5 mmol.l-1)
timeFrame: 6 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital PITIE-SALPETRIERE - Institut de Cardiologie
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Farzin BEYGUI, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Beygui F, Cayla G, Roule V, Roubille F, Delarche N, Silvain J, Van Belle E, Belle L, Galinier M, Motreff P, Cornillet L, Collet JP, Furber A, Goldstein P, Ecollan P, Legallois D, Lebon A, Rousseau H, Machecourt J, Zannad F, Vicaut E, Montalescot G; ALBATROSS Investigators. Early Aldosterone Blockade in Acute Myocardial Infarction: The ALBATROSS Randomized Clinical Trial. J Am Coll Cardiol. 2016 Apr 26;67(16):1917-27. doi: 10.1016/j.jacc.2016.02.033.
citation: Beygui F, Vicaut E, Ecollan P, Machecourt J, Van Belle E, Zannad F, Montalescot G. Rationale for an early aldosterone blockade in acute myocardial infarction and design of the ALBATROSS trial. Am Heart J. 2010 Oct;160(4):642-8. doi: 10.1016/j.ahj.2010.06.049.