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Aldosterone Blockade Early After Acute Myocardial Infarction (ALBATROSS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01059136
First received: January 28, 2010
Last updated: August 25, 2014
Last verified: August 2014
History of Changes
  Purpose

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 Intervention Phase
Myocardial Infarction
 Drug: Spironolactone
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

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. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Any of the criteria of the primary endpoint [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • primary endpoint+ myocardial infarction+stroke cardiovascular death [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • death + resuscitated cardiac arrest [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Death+resuscitated cardiac arrest+ventricular arrhythmia+indication for implantable defibrillator device [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • death+heart failure [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Acute renal failure [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • primary endpoint [ Time Frame: hospital discharge and 30 days ] [ Designated as safety issue: Yes ]
  • rate of hyperkaliemia (> 5.5 mmol.l-1) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Enrollment: 1600
Study Start Date: February 2010
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: Spironolactone
No Intervention: 2:Standard therapy
Standard therapy

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
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01059136

Locations
France
Hôpital PITIE-SALPETRIERE - Institut de Cardiologie
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Farzin BEYGUI, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided by Assistance Publique - Hôpitaux de Paris

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01059136     History of Changes
Other Study ID Numbers: P071216
Study First Received: January 28, 2010
Last Updated: August 25, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Myocardial infarction
Outcome
Aldosterone
Spironolactone

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Cardiovascular Diseases
Heart Diseases
Ischemia
Myocardial Ischemia
Necrosis
Pathologic Processes
Vascular Diseases
Spironolactone
 Cardiovascular Agents
Diuretics
Diuretics, Potassium Sparing
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015