Aldosterone Blockade Early After Acute Myocardial Infarction

Myocardial Infarction Clinical Trial

— ALBATROSS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01059136
• Other study ID #: P071216
• Status: Completed
• Phase: Phase 3
• First received: January 28, 2010
• Last updated: June 10, 2015
• Start date: February 2010
• Est. completion date: August 2014

Study information

• Verified date: June 2015
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1603
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

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

Locations

Country	Name	City	State
France	Hôpital PITIE-SALPETRIERE - Institut de Cardiologie	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Any of the criteria of the primary endpoint		6 months	Yes
Secondary	primary endpoint+ myocardial infarction+stroke cardiovascular death		6 months	Yes
Secondary	death + resuscitated cardiac arrest		6 months	Yes
Secondary	Death+resuscitated cardiac arrest+ventricular arrhythmia+indication for implantable defibrillator device		6 months	Yes
Secondary	death+heart failure		6 months	Yes
Secondary	Acute renal failure		6 months	Yes
Secondary	primary endpoint		hospital discharge and 30 days	Yes
Secondary	rate of hyperkaliemia (> 5.5 mmol.l-1)		6 months	Yes