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

NCT01005602 | Completed Phase 4 Results

• 2 other identifiers: ACCP 2006-072008-05762
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Failure

Keywords

Digoxin; Pharmacokinetics; Dosing; Heart Failure

Outcome Measures

Primary Outcomes (1)

• Percent of Patients Achieving a Desired Steady-state Serum Digoxin Concentration Between 0.5 - 0.9ng/ml

  Steady-state (2 - 4 weeks after initiation)

Secondary Outcomes (5)

• Mean Serum Digoxin Concentration

  Steady-state (2 - 4 weeks after initiation)

• Serum Digoxin Concentration < 1.0 ng/ml

  Steady-state (2 - 4 weeks after initiation)

• Serum Digoxin Concentration by ABCB1 Single Nucleotide Polymorphism (SNP) C1236T

  Steady-state (2 - 4 weeks after initiation)

• Serum Digoxin Concentration by ABCB1 SNP C3435T

  Steady-state (2 - 4 weeks after initiation)

• Serum Digoxin Concentration by ABCB1 SNP G2677T/A

  Steady-state (2 - 4 weeks after initiation)

Study Arms (2)

Digoxin Dosing per Nomogram

EXPERIMENTAL

Subjects will have their digoxin maintenance dose determined according to the nomogram we have developed.

Other: Digoxin Dosing per Nomogram; Drug: Digoxin

Standard Digoxin Dosing

OTHER

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

Interventions

Digoxin Dosing per Nomogram OTHER

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).

Digoxin Dosing per Nomogram

Digoxin DRUG

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.

Also known as: Lanoxin

Digoxin Dosing per Nomogram; Standard Digoxin Dosing

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• American College of Clinical Pharmacy: collaborator

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Related Publications (2)

• Bauman JL, DiDomenico RJ, Viana M, Fitch M. A method of determining the dose of digoxin for heart failure in the modern era. Arch Intern Med. 2006 Dec 11-25;166(22):2539-45. doi: 10.1001/archinte.166.22.2539.

  PMID: 17159022 BACKGROUND

• DiDomenico RJ, Bress AP, Na-Thalang K, Tsao YY, Groo VL, Deyo KL, Patel SR, Bishop JR, Bauman JL. Use of a simplified nomogram to individualize digoxin dosing versus standard dosing practices in patients with heart failure. Pharmacotherapy. 2014 Nov;34(11):1121-31. doi: 10.1002/phar.1480. Epub 2014 Aug 28.

  PMID: 25164709 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Digoxin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Results Point of Contact

• Title: Dr. Robert J. DiDomenico
• Organization: University of Illinois at Chicago

rdidom1@uic.edu

(312) 413-4654

Study Officials

• Robert J DiDomenico, PharmD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: October 30, 2009
• First Posted: November 2, 2009
• Study Start: December 1, 2006
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: May 22, 2014
• Results First Posted: May 19, 2014

Record last verified: 2014-05

Locations

US (1)