Digoxin Dosing in Heart Failure: A Simplified Nomogram Versus Standard Care
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Purpose
| Condition | Intervention | Phase |
|---|---|---|
|
Heart Failure |
Other: Digoxin Dosing per Nomogram Drug: 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 |
- 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: No ]
- Mean Serum Digoxin Concentration [ Time Frame: Steady-state (2 - 4 weeks after initiation) ] [ Designated as safety issue: No ]
- Serum Digoxin Concentration < 1.0 ng/ml [ Time Frame: Steady-state (2 - 4 weeks after initiation) ] [ Designated as safety issue: No ]
- Serum Digoxin Concentration by ABCB1 Single Nucleotide Polymorphism (SNP) C1236T [ Time Frame: Steady-state (2 - 4 weeks after initiation) ] [ Designated as safety issue: No ]55 patients in the Digoxin Dosing per Nomogram group consented to the Pharmacogenetic substudy and provided blood samples to perform pharmacogenetic analyses. We compared serum digoxin concentrations by ABCB1 genotype.
- Serum Digoxin Concentration by ABCB1 SNP C3435T [ Time Frame: Steady-state (2 - 4 weeks after initiation) ] [ Designated as safety issue: No ]Serum digoxin concentration by genotypes for the ABCB1 SNP C3435T
- Serum Digoxin Concentration by ABCB1 SNP G2677T/A [ Time Frame: Steady-state (2 - 4 weeks after initiation) ] [ Designated as safety issue: No ]Serum digoxin concentration by ABCB1 SNP genotypes
| Enrollment: | 131 |
| Study Start Date: | December 2006 |
| Study Completion Date: | December 2009 |
| 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: Digoxin Dosing per Nomogram
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).
Drug: Digoxin
All patients included in the trial were treated with digoxin as clinically indicated. The intervention for this study required determining the digoxin dose via a proposed nomogram.
Other Name: Lanoxin
|
|
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.
|
Drug: Digoxin
All patients included in the trial were treated with digoxin as clinically indicated. The intervention for this study required determining the digoxin dose via a proposed nomogram.
Other Name: Lanoxin
|
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 (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01005602
| United States, Illinois | |
| University of Illinois at Chicago | |
| Chicago, Illinois, United States, 60612 | |
| Principal Investigator: | Robert J DiDomenico, PharmD | University of Illinois at Chicago |
More Information
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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 |
| Results First Received: | April 16, 2014 |
| Last Updated: | May 19, 2014 |
| 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 Anti-Arrhythmia Agents |
Cardiotonic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on September 27, 2016