Effects of Beta-Blocker Therapy and Phosphodiesterase Inhibition on Cardiac Neurohormonal Activation

May 29, 2007 updated by: Klinikum Ludwigshafen

The Influence of Continuous Perioperative Beta-Blocker Therapy in Combination With Phosphodiesterase Inhibition on Cardiac Neurohormonal Activation and Myocardial Ischaemia in High-Risk Vascular Surgery Patients

Previous clinical investigations have demonstrated the utility of β-adrenergic blockade in reducing perioperative ischaemic events, ultimately translating into a decrease in cardiac morbidity and mortality. However, β-blocker therapy remains underutilized in clinical practice because of concerns of potential adverse effects such as a reduced inotropic state, which might result in acute congestive heart failure or hypotension. Therefore, additional treatment with a positive inotropic agent might be needed. Phosphodiesterase inhibitors (PDEIs) offer a favourable pharmacological profile in this setting and stimulate cardiac function in the absence of the β-adrenergic receptor.

We hypothesize that the combination of PDEI and β-blocker therapy would decrease perioperative plasma concentrations of brain natriuretic peptide (BNP) in patients requiring major vascular surgery. BNP is chosen as our primary outcome variable because of its importance as a sensitive correlate of myocardial dysfunction and its prognostic value for predicting the risk of cardiac death across the entire spectrum of acute coronary syndromes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cardiac complications, such as, myocardial infarction, heart failure, and life-threatening dysrhythmias, are the leading cause of perioperative death among patients undergoing major vascular surgery.

The pathogenesis of perioperative ischaemic events is most certainly multifactorial and includes persistent activation of several neurohormonal pathways, such as the natriuretic peptide system.

Previous clinical investigations have demonstrated the utility of β-adrenergic blockade in reducing perioperative ischaemic events, ultimately translating into a decrease in cardiac morbidity and mortality especially in patients who had or were at high risk for coronary artery disease. Therefore, the administration of β-blockers to all patients at high risk for coronary events who are scheduled to undergo major noncardiac surgery is strongly supported by consensus recommendations and clinical guidelines. Despite the evidence of benefit, β-blockers remain underutilized in clinical practice because of concerns of potential adverse effects such as a reduced inotropic state, which might result in myocardial depression, acute congestive heart failure, and hypotension [13]. Therefore, additional treatment with a positive inotropic agent might be needed.

Phosphodiesterase inhibitors (PDEIs) offer a favourable pharmacological profile in this setting and retain their haemodynamic effects in the face of full β-blockade. Preliminary data suggest that the combination of PDEI and β-blocker therapy may be better tolerated and allows for expression of the known effects of β-blocker therapy and improved myocardial functioning without the adverse effects of either therapy alone.

We therefore hypothesize that the combination of PDEI and β-blocker therapy would decrease perioperative plasma concentrations of brain natriuretic peptide (BNP) in patients requiring major vascular surgery documented to have a high prevalence of coronary artery disease and limited coronary reserve. BNP is chosen because of its pivotal role as a sensitive correlate of myocardial dysfunction and its prognostic value for predicting the short- and long-term risk of cardiac death across the entire spectrum of acute coronary syndromes.

Study Type

Interventional

Enrollment (Actual)

75

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Ludwigshafen, Germany, 67063
        • Department of Anesthesiology and Intensive Care Medicine Klinikum Ludwigshafen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • scheduled for major vascular surgery
  • can sign informed consent before surgery
  • documented CAD or risk factors for CAD

Exclusion Criteria:

  • Preoperative treatment with beta-adrenergic agonists or glucocorticoids,
  • electrocardiographic (ECG) abnormalities like nonsinus rhythm, second- or third degree heart block, or left bundle branch block,
  • cardiac pacemaker dependency,
  • symptomatic mitral or aortic valvular disease,
  • a history of asthma, bronchospasm, or severe chronic obstructive pulmonary disease necessitating bronchodilator therapy,
  • severe liver dysfunction
  • known allergies against the study drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure
We hypothesize that the combination of PDEI and β-blocker therapy
would decrease perioperative plasma concentrations of brain natriuretic peptide
BNP) in patients requiring major vascular surgery.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Klinikum Ludwigshafen

Investigators

  • Principal Investigator: Stefan Suttner, M.D., Aarhus University hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Study Completion (Actual)

May 1, 2007

Study Registration Dates

First Submitted

July 3, 2006

First Submitted That Met QC Criteria

July 3, 2006

First Posted (Estimate)

July 4, 2006

Study Record Updates

Last Update Posted (Estimate)

May 30, 2007

Last Update Submitted That Met QC Criteria

May 29, 2007

Last Verified

April 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ESPEKLILU05

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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