Heart FailurePhase 4NCT01005602
Digoxin Dosing in Heart Failure: A Simplified Nomogram Versus Standard Care
A Phase 4 study testing Digoxin Dosing per Nomogram and Digoxin in people with Heart Failure, run by University of Illinois at Chicago at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Digoxin Dosing per Nomogram and Digoxin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 131 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Dec 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 21 years
- Diagnosis of heart failure secondary to left ventricular dysfunction
- Receiving chronic digoxin therapy or digoxin therapy is being initiated
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Illinois at Chicago
Chicago, Illinois, 60612
About this study
Official title: Use of a Simplified Nomogram and Pharmacogenetics to Individualize Digoxin Dosing in Heart Failure Patients vs. Standard Care
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.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- Digoxin Dosing per Nomogram, Digoxin
- Keywords
- Digoxin, Pharmacokinetics, Dosing, Heart Failure
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Digoxin Dosing per NomogramOther
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).
DigoxinDrug
Also called Lanoxin
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.
| Study group | Role | What they receive |
|---|---|---|
| Digoxin Dosing per Nomogram | Experimental | Subjects will have their digoxin maintenance dose determined according to the nomogram we have developed. Receives: 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. Receives: Drug: Digoxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Patients Achieving a Desired Steady-state Serum Digoxin Concentration Between 0.5 - 0.9ng/ml
Measured: Steady-state (2 - 4 weeks after initiation)
Secondary outcomes (5)
Mean Serum Digoxin Concentration
Measured: Steady-state (2 - 4 weeks after initiation)
Serum Digoxin Concentration < 1.0 ng/ml
Measured: Steady-state (2 - 4 weeks after initiation)
Serum Digoxin Concentration by ABCB1 Single Nucleotide Polymorphism (SNP) C1236T
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.
Measured: Steady-state (2 - 4 weeks after initiation)
Serum Digoxin Concentration by ABCB1 SNP C3435T
Serum digoxin concentration by genotypes for the ABCB1 SNP C3435T
Measured: Steady-state (2 - 4 weeks after initiation)
Serum Digoxin Concentration by ABCB1 SNP G2677T/A
Serum digoxin concentration by ABCB1 SNP genotypes
Measured: Steady-state (2 - 4 weeks after initiation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2009 (estimated)
- Study startDec 2006
- Primary completionDec 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois at Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- American College of Clinical Pharmacy
- Responsible party
- Principal investigator, Robert J. DiDomenico, University of Illinois at Chicago
- Investigators
- Robert J DiDomenico, PharmD, Principal investigator, University of Illinois at Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01005602
- Sponsor's protocol ID
- ACCP 2006-07
- Other IDs
- 2008-05762, 2008
- Status last verified
- May 2014
- First submitted
- 30 Oct 2009
- Last updated
- 22 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 17159022DiDomenico 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.
PubMed 25164709
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of a Simplified Nomogram and Pharmacogenetics to Individualize Digoxin Dosing in Heart Failure Patients vs. Standard Care
- ClinicalTrials.gov ID
- NCT01005602
- Acronym / sponsor ID
- ACCP 2006-07
- Conditions
- Heart Failure
- Keywords
- Digoxin, Pharmacokinetics, Dosing, Heart Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- University of Illinois at ChicagoUniversity, hospital or other
- Collaborators
- American College of Clinical Pharmacy
- Study start
- Dec 2006
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 2 Nov 2009 (estimated)
- Results
- Posted 19 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Digoxin Dosing per Nomogram | Experimental | Other: Digoxin Dosing per Nomogram, Drug: DigoxinSubjects will have their digoxin maintenance dose determined according to the nomogram we have developed. |
| Standard Digoxin Dosing | Other | Drug: DigoxinThis arm represents historical control subjects in whom the dose of digoxin was determined at the physician's discretion using traditional dosing methods. |
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age > 21 years
- Diagnosis of heart failure secondary to left ventricular dysfunction
- Receiving chronic digoxin therapy or digoxin therapy is being initiated
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Digoxin Dosing per NomogramSimplified 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). | Other | Digoxin Dosing per Nomogram |
| DigoxinAlso: LanoxinAll 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. | Drug | Digoxin Dosing per Nomogram, Standard Digoxin Dosing |
Primary outcome
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)
5 secondary outcomes
Mean Serum Digoxin Concentration
Time frame: Steady-state (2 - 4 weeks after initiation)
Serum Digoxin Concentration < 1.0 ng/ml
Time frame: Steady-state (2 - 4 weeks after initiation)
Serum Digoxin Concentration by ABCB1 Single Nucleotide Polymorphism (SNP) C1236T
Time frame: Steady-state (2 - 4 weeks after initiation)
Serum Digoxin Concentration by ABCB1 SNP C3435T
Time frame: Steady-state (2 - 4 weeks after initiation)
Serum Digoxin Concentration by ABCB1 SNP G2677T/A
Time frame: Steady-state (2 - 4 weeks after initiation)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17159022Bauman 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.
- Derived from this study: PubMed 25164709DiDomenico 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert J DiDomenico, PharmD principal investigator
University of Illinois at Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Digoxin Dosing per Nomogram and Digoxin in people with Heart Failure, run by University of Illinois at Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01005602, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2014.