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

This study has suspended participant recruitment.
Sponsor:
Information provided by (Responsible Party):
Anna Stein, Federal University of São Paulo
ClinicalTrials.gov Identifier:
NCT01154504
First received: June 28, 2010
Last updated: November 4, 2011
Last verified: November 2011
  Purpose
  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.

Condition Intervention
Heart Failure
Other: clinical treatment
Procedure: ultrafiltration
Procedure: isovolumetric hemofiltration

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Role of Adrenomedullin on the Outcome of Severe Heart Failure: a Clinical Randomized Study

Resource links provided by NLM:


Further study details as provided by Federal University of São Paulo:

Primary Outcome Measures:
  • Levels of Adrenomedullin plasma in different treatments- clinical,ultrafiltration and isovolumetric hemofiltration [ Time Frame: 90 days after randomization (plus or minus 3 days). ] [ Designated as safety issue: Yes ]
    The adrenomedullin level will be compared in three different treatments: clinical treatment, ultrafiltration treatment and isovolumetric hemofiltration.

  • Levels of Adrenomedullin plasma in different treatments- clinical,ultrafiltration and isovolumetric hemofiltration [ Time Frame: at discharge ] [ Designated as safety issue: Yes ]
    The adrenomedullin level will be compared in three different treatments: clinical treatment, ultrafiltration treatment and isovolumetric hemofiltration. The patients will be followed until discharge.


Secondary Outcome Measures:
  • The Adrenomedullin plasma levels in three different treatment approaches will be related to clinical outcome. [ Time Frame: at discharge ] [ Designated as safety issue: Yes ]
    The correlation of adrenomedullin plasma levels in all 3 arms related to optimized clinical outcome. The patients will be followed until discharge

  • The Adrenomedullin plasma levels in three different treatment approaches will be related to clinical outcome. [ Time Frame: 90 days after randomization (plus or minus 3) ] [ Designated as safety issue: Yes ]
    The correlation of adrenomedullin plasma levels in all 3 arms related to optimized clinical outcome.

  • The Adrenomedullin plasma levels in three different treatment approaches will be related to oxydative stress [ Time Frame: at discharge ] [ Designated as safety issue: Yes ]
    The correlation of adrenomedullin plasma levels in all 3 arms related to oxydative stress. The patients will be followed until discharge.

  • The Adrenomedullin plasma levels in three different treatment approaches will be related to oxydative stress [ Time Frame: 90 days after randomization(plus or minus 3) ] [ Designated as safety issue: Yes ]
    The correlation of adrenomedullin plasma levels in all 3 arms related to oxydative stress.

  • The Adrenomedullin plasma levels in three different treatment approaches will be related to angiotensin II plasma level [ Time Frame: at discharge ] [ Designated as safety issue: Yes ]
    The correlation of adrenomedullin plasma levels in all 3 arms related to angiotensin II level. The patients will be followed until discharge.

  • The Adrenomedullin plasma levels in three different treatment approaches will be related to angiotensin II plasma level [ Time Frame: 90 days after randomization(plus or minus 3) ] [ Designated as safety issue: Yes ]
    The correlation of adrenomedullin plasma levels in all 3 arms related to angiotensin II plasma level.

  • The Adrenomedullin plasma levels in three different treatment approaches will be related to Brain natriuretic peptide plasma level [ Time Frame: at discharge ] [ Designated as safety issue: Yes ]
    The correlation of adrenomedullin plasma levels in all 3 arms related to Brain natriuretic peptide level. The patients will be followed until discharge.

  • The Adrenomedullin plasma levels in three different treatment approaches will be related to Pro-Brain natriuretic peptide plasma level [ Time Frame: 90 days after randomization(plus or minus 3) ] [ Designated as safety issue: Yes ]
    The correlation of adrenomedullin plasma levels in all 3 arms related to Brain natriuretic peptide level, 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 [ Time Frame: at discharge ] [ Designated as safety issue: Yes ]
    The correlation of adrenomedullin plasma levels in all 3 arms related to sympathetic nervous system.The patients will be followed until discharge.

  • The Adrenomedullin plasma levels in three different treatment approaches will be related to sympathetic nervous system activity [ Time Frame: 90 days after randomization(plus or minus 3) ] [ Designated as safety issue: Yes ]
    The correlation of adrenomedullin plasma levels in all 3 arms related to sympathetic nervous system.


Estimated Enrollment: 51
Study Start Date: April 2010
Estimated Study Completion Date: December 2012
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • clinical treatment
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:
  • ultrafiltration
  • dialysis
  • adrenomedullin
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:
  • hemofiltration
  • dialysis
  • adrenomedullin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01154504

Locations
Brazil
Instituto de Cardiologia
Porto Alegre, Rio Grande do Sul, Brazil, 94801970
Sponsors and Collaborators
Federal University of São Paulo
  More Information

No publications provided

Responsible Party: Anna Stein, MD, Federal University of São Paulo
ClinicalTrials.gov Identifier: NCT01154504     History of Changes
Other Study ID Numbers: CEP1781/07
Study First Received: June 28, 2010
Last Updated: November 4, 2011
Health Authority: Brazil: Ethics Committee

Keywords provided by Federal University of São Paulo:
adrenomedullin
heart failure
ultrafiltration
hemofiltration

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Natriuretic Peptide, Brain
Adrenomedullin
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Cardiotonic Agents
Vasodilator Agents
Protective Agents

ClinicalTrials.gov processed this record on August 19, 2014