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

Not Applicable

Withdrawn

• Conditions: Heart Failure
• Interventions: Other: clinical treatment; Procedure: isovolumetric hemofiltration; Procedure: ultrafiltration

• Registration Number: NCT01154504
• Lead Sponsor: Federal University of São Paulo

Brief Summary

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.

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 Timeline

• Study Start: 2010-04
• Study First Submitted: 2010-06-28
• Study First Submitted QC: 2010-06-30
• Study First Posted: 2010-07-01
• Primary Completion: 2010-12
• Study Completion: 2012-12
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-02
• Last Update Posted: 2016-11-04

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
clinical treatment	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).
isovolumetric hemofiltration	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).
ultrafiltration	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.

Primary Outcome Measures

Name	Time	Method
Levels of Adrenomedullin plasma in different treatments- clinical,ultrafiltration and isovolumetric hemofiltration	at discharge	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

Name	Time	Method
The Adrenomedullin plasma levels in three different treatment approaches will be related to clinical outcome.	90 days after randomization (plus or minus 3)	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	90 days after randomization(plus or minus 3)	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	90 days after randomization(plus or minus 3)	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	at discharge	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	90 days after randomization(plus or minus 3)	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	90 days after randomization(plus or minus 3)	The correlation of adrenomedullin plasma levels in all 3 arms related to sympathetic nervous system.

Trial Locations

Locations (1)

Instituto de Cardiologia; 🇧🇷 Porto Alegre, Rio Grande do Sul, Brazil