The Role of Adrenomedullin on the Outcome of Severe Heart Failure: a Clinical Randomized Study

1. Study Hypothesis:

   • The decrease of plasma adrenomedullin (ADM) concentration by ultrafiltration and isovolumetric hemofiltration in patients with acute III and IV Class New York Heart Association Functional(NYHA) heart failure is more pronounced than a standard diuretic treatment and is related with clinical improvement.
2. Outcome Measurements:

To correlate the adrenomedullin plasma levels with clinical treatment, ultrafiltration and hemofiltration related to:

• Brain natriuretic peptide (BNP) level
• angiotensin II level
• sympathetic nervous activity
• oxydative stress
• clinical outcome at the beginning, at discharge and 90 days after randomization.

Study Overview

• Status: Withdrawn
• Conditions: Heart Failure
• Intervention / Treatment: Other: clinical treatment; Procedure: ultrafiltration; Procedure: isovolumetric hemofiltration

Detailed Description

Testing the hypothesis that adrenomedullin (ADM) is a important peptide in severe heart failure and that is related to clinical condition, we will study the effects of 3 different treatments (clinical usual treatment,ultrafiltration and isovolumetric hemofiltration with diuretics) to participants are followed until discharge to Adrenomedullin level and clinical outcomes,and also their relationship with angiotensin II level, brain natriuretic peptide(BNP), sympathetic nervous system and oxydative stress.

The patients will be randomized in three different treatment group and analyzed in three moments: on the randomization, at discharge and 90 days after randomization(plus or minus 3).

The clinical treatment will be optimized, the ultrafiltration will be done until clinically adequate fluid removal or until hematocrit increased 10% from basal level, and isovolumetric hemofiltration will be done for 8 hours- dose of 35 ml/kg/h in association with diuretic. All this dialytic procedures will be done with PAES membrane- filter HF1400 and automatic machine.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 94801970
      • Instituto de Cardiología

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• more than two item:

  • more than eighteen years of age
  • orthopnea
  • Chest Rx with cardiomegaly and pulmonary infiltration
  • edema
  • diuretic resistance

Exclusion Criteria:

• insulin dependent diabetes
• hepatic cirrhosis
• vascular access problems
• creatinine more than 2,5 mg/dl before acute heart failure
• systemic infection
• aortic stenosis and heart transplantation
• radiologic contrast up to 72 hours prior randomization
• advanced neoplasia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: clinical treatment; Patients with previous diagnosis of decompensated III and IV Heart Failure will be included. The clinical treatment will be optimized. Clinical assessment, Adrenomedullin, Angiotensin II, Brain Natriuretic Peptide, oxydative stress, sympathetic nervous system activity will be evaluated at the beginning, at discharge and 90 days after randomization(plus or minus3).	Other: clinical treatment; The clinical treatment will be optimized to gold standard international heart failure treatment; Other Names: adrenomedullin
Experimental: ultrafiltration; ultrafiltration will be done on decompensated patients III and IV acute heart failure on Intensive Care Unit. This patients will have biochemical analysis, adrenomedullin, angiotensin II,Brain Natriuretic Peptide, oxydative stress measurements,sympathetic nervous system activity evaluated and clinical outcome analyzed at the beginning,at discharge and 90 days after randomization(plus or minus 3). Diuretic will be withdrawn during ultrafiltration.	Procedure: ultrafiltration; The ultrafiltration procedure will be done on Intensive Care Unit with automatic machine and HF 1400 filter. The fluid will be removed until a increased of 10% in hematocrit or clinical improvement.; Other Names: adrenomedullin; dialysis
Experimental: isovolumetric hemofiltration; Patients randomized to this group will have isovolumetric hemofiltration on Intensive Care Unit. They will have biochemical analysis, Adrenomedullin plasmatic level, Brain Natriuretic Peptide Level, Angiotensin II level, Oxydative stress measurement,sympathetic nervous system, and clinical outcome evaluated at the study beginning,at discharge and 90 days after randomization(plus or minus 3).	Procedure: isovolumetric hemofiltration; The isovolumetric hemofiltration will be done in Intensive Care Unit for 8 hours, and will be permitted the diuretic use.The dose will be 35 ml/kg/hour and will e used automatic machine and MF1400 filter.Diuretic use will be maintained.; Other Names: adrenomedullin; dialysis; hemofiltration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of Adrenomedullin plasma in different treatments- clinical,ultrafiltration and isovolumetric hemofiltration	The adrenomedullin level will be compared in three different treatments: clinical treatment, ultrafiltration treatment and isovolumetric hemofiltration.	90 days after randomization (plus or minus 3 days).
Levels of Adrenomedullin plasma in different treatments- clinical,ultrafiltration and isovolumetric hemofiltration	The adrenomedullin level will be compared in three different treatments: clinical treatment, ultrafiltration treatment and isovolumetric hemofiltration. The patients will be followed until discharge.	at discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Adrenomedullin plasma levels in three different treatment approaches will be related to clinical outcome.	The correlation of adrenomedullin plasma levels in all 3 arms related to optimized clinical outcome. The patients will be followed until discharge	at discharge
The Adrenomedullin plasma levels in three different treatment approaches will be related to clinical outcome.	The correlation of adrenomedullin plasma levels in all 3 arms related to optimized clinical outcome.	90 days after randomization (plus or minus 3)
The Adrenomedullin plasma levels in three different treatment approaches will be related to oxydative stress	The correlation of adrenomedullin plasma levels in all 3 arms related to oxydative stress. The patients will be followed until discharge.	at discharge
The Adrenomedullin plasma levels in three different treatment approaches will be related to oxydative stress	The correlation of adrenomedullin plasma levels in all 3 arms related to oxydative stress.	90 days after randomization(plus or minus 3)
The Adrenomedullin plasma levels in three different treatment approaches will be related to angiotensin II plasma level	The correlation of adrenomedullin plasma levels in all 3 arms related to angiotensin II level. The patients will be followed until discharge.	at discharge
The Adrenomedullin plasma levels in three different treatment approaches will be related to angiotensin II plasma level	The correlation of adrenomedullin plasma levels in all 3 arms related to angiotensin II plasma level.	90 days after randomization(plus or minus 3)
The Adrenomedullin plasma levels in three different treatment approaches will be related to Brain natriuretic peptide plasma level	The correlation of adrenomedullin plasma levels in all 3 arms related to Brain natriuretic peptide level. The patients will be followed until discharge.	at discharge
The Adrenomedullin plasma levels in three different treatment approaches will be related to Pro-Brain natriuretic peptide plasma level	The correlation of adrenomedullin plasma levels in all 3 arms related to Brain natriuretic peptide level, 90 days after randomization(plus or minus 3)	90 days after randomization(plus or minus 3)
The Adrenomedullin plasma levels in three different treatment approaches will be related to sympathetic nervous system activity	The correlation of adrenomedullin plasma levels in all 3 arms related to sympathetic nervous system.The patients will be followed until discharge.	at discharge
The Adrenomedullin plasma levels in three different treatment approaches will be related to sympathetic nervous system activity	The correlation of adrenomedullin plasma levels in all 3 arms related to sympathetic nervous system.	90 days after randomization(plus or minus 3)

Collaborators and Investigators

• Sponsor: Federal University of São Paulo

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: June 28, 2010
• First Submitted That Met QC Criteria: June 30, 2010
• First Posted (Estimate): July 1, 2010

Study Record Updates

• Last Update Posted (Estimate): November 4, 2016
• Last Update Submitted That Met QC Criteria: November 2, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: heart failure; ultrafiltration; adrenomedullin; hemofiltration
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Cardiotonic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenomedullin
• Other Study ID Numbers: CEP1781/07