Digoxin Dosing in Heart Failure: A Simplified Nomogram Versus Standard Care

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2009 by University of Illinois at Chicago.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
University of Illinois at Chicago
ClinicalTrials.gov Identifier:
NCT01005602
First received: October 30, 2009
Last updated: NA
Last verified: October 2009
History: No changes posted
  Purpose

Dosing methods for digoxin, a drug used to treat heart failure, have not been updated in decades despite evidence in recent years suggesting that blood levels of digoxin achieved with traditional dosing practices may increase the risk of adverse events. We developed a simple dosing tool that targets lower blood levels of digoxin that have been associated with improved outcomes compared to higher blood levels. The aim of this study is to determine if this simplified dosing tool is more effective than standard digoxin dosing practices at achieving lower blood levels and also to determine if digoxin dosing may be further optimized by incorporating patients' genetic information believed to influence the drug's properties.


Condition Intervention Phase
Heart Failure
Other: Dosing nomogram for digoxin
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Use of a Simplified Nomogram and Pharmacogenetics to Individualize Digoxin Dosing in Heart Failure Patients vs. Standard Care

Resource links provided by NLM:


Further study details as provided by University of Illinois at Chicago:

Primary Outcome Measures:
  • Percent of patients achieving a desired steady-state serum digoxin concentration between 0.5 - 0.9ng/ml [ Time Frame: Steady-state (2 - 4 weeks after initiation) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Difference in steady-state serum digoxin concentrations across C3435T genotypes [ Time Frame: Steady-state (2 - 4 weeks after initiation) ] [ Designated as safety issue: No ]
  • Steady-state serum digoxin concentration between TTT haplotype carriers and non-carriers [ Time Frame: Steady-state (2 - 4 weeks after initiation) ] [ Designated as safety issue: No ]

Estimated Enrollment: 170
Study Start Date: December 2006
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Digoxin Dosing per Nomogram
Subjects will have their digoxin maintenance dose determined according to the nomogram we have developed.
Other: Dosing nomogram for digoxin
Simplified dosing nomogram for digoxin. The dose is determined by plotting a subject's creatinine clearance (x-axis) and ideal body weight (y-axis) on the nomogram. Alternatively, the dose may be determined by plotting creatinine clearance (x-axis) and gender/height (z-axis).
No Intervention: Standard Digoxin Dosing
This arm represents historical control subjects in whom the dose of digoxin was determined at the physician's discretion using traditional dosing methods.

Detailed Description:

Digoxin is recommended as adjunctive therapy in patients with left ventricular dysfunction and symptoms of heart failure despite treatment with standard therapy. Recently, the therapeutic range for digoxin in patients with heart failure has been redefined to a narrower therapeutic window (0.5 - 0.9 ng/ml) because lower serum levels in this range have been associated with improved survival whereas higher serum levels have been associated with increased mortality. However, dosing methods have not been updated to reflect the newly defined therapeutic range for digoxin. We developed a simplified dosing nomogram for digoxin in patients with heart failure designed to achieve serum digoxin concentrations (SDC) within the new therapeutic range using retrospective data. The long-term goal of this study is to prospectively validate the ability of our digoxin dosing nomogram to achieve desired SDC and provide clinicians a simplified tool to optimize digoxin dosing in patients with heart failure. Because digoxin is a substrate of the efflux pump p-glycoprotein (pGP) and genetic polymorphisms of the MDR1 gene (known to regulate pGP expression) have demonstrated conflicting results on the pharmacokinetic profile of digoxin, we will also characterize the influence MDR1 functional gene variants may have on digoxin dosing. This study will include a total of 170 subjects with symptomatic heart failure treated with digoxin, comparing steady-state SDC in a prospective group of patients dosed according to our nomogram to a historical control group in whom the dose of digoxin was derived from standard dosing practices. We will also conduct an analysis of genetic polymorphisms of the MDR1 gene known to affect digoxin pharmacokinetics. The primary objectives of the study are to compare the percentage of patients in each group achieving steady-state SDC within the desired range of 0.5 - 0.9 ng/ml, characterize the relationship between genetic variability in the MDR1 gene and digoxin dosing, and to update our digoxin dosing nomogram to account for the clinical and genetic variability shown to have the greatest influence on digoxin dosing. The rationale for this study is that lower doses of digoxin are recommended because lower SDC are associated with improved survival. Therefore, digoxin dosing methods must be updated to reflect these recommendations and account for genetic variability of the MDR1 gene in an effort to improve clinical outcomes and minimize the potential for adverse events. To address these issues, the specific aims of this research are:

Aim 1: Compare steady-state SDC observed using our dosing nomogram to those obtained using standard dosing practices.

Aim 2: Characterize the relationship of the genetic variability of the MDR1 gene and SDC observed using our digoxin dosing nomogram.

  Eligibility

Ages Eligible for Study:   22 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 21 years
  • Diagnosis of heart failure secondary to left ventricular dysfunction
  • Receiving chronic digoxin therapy or digoxin therapy is being initiated

Exclusion Criteria:

  • Pregnant
  • Unstable renal function, defined as either a rise in serum creatinine by > 0.5mg/dl from baseline or a decrease in creatinine clearance by 25% or more within two to four weeks of study entry.
  • End-stage renal disease requiring hemodialysis
  • Concomitant therapy with drugs known to interact with digoxin (e.g., amiodarone, quinidine, verapamil, macrolide antibiotics)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01005602

Locations
United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
University of Illinois at Chicago
Investigators
Principal Investigator: Robert J DiDomenico, PharmD University of Illinois at Chicago
  More Information

Publications:
Responsible Party: Robert J. DiDomenico/Clinical Associate Professor, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT01005602     History of Changes
Other Study ID Numbers: ACCP 2006-07, 2008-05762
Study First Received: October 30, 2009
Last Updated: October 30, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by University of Illinois at Chicago:
Digoxin
Pharmacokinetics
Dosing
Heart Failure

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Digoxin
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014