Heart Failure, CongestivePhase 3NCT00077948
Enoximone Plus Extended-Release Metoprolol Succinate in Subjects With Advanced Chronic Heart Failure
A Phase 3 study testing Enoximone and Metoprolol succinate in people with Heart Failure, Congestive, run by Gilead Sciences at 2 sites in United States.
Trial summary
Beta-blocker medications have been shown to improve heart function and prolong the lives of patients with chronic heart failure (CHF). Some people with advanced CHF have difficulty taking beta-blocker medications due to troublesome side effects, such as low blood pressure and/or low heart rate, severe tiredness… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Congestive
- What is being tested?
- Enoximone and Metoprolol succinate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 175 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2003to Jun 2005
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In order to be considered an eligible subject, all of the following entry criteria must be met:
- Subjects must be competent to provide informed written consent. Subjects must sign an IRB/IEC approved informed consent form prior to the initiation of any study procedures.
- Subjects must be 18 years of age or older.
- Subjects must have ischemic or nonischemic cardiomyopathy with symptoms of NYHA Class III or IV chronic heart failure.
- Subjects must have a LVEF of less than or equal to 35%, measured within 60 days of the Screening Visit. LVEF must be assessed by radionuclide ventriculography (MUGA). If the subject has experienced any cardiovascular events, has undergone any interventions, or received any changes in treatment that may have affected LV function since the most recent EF measurement, an LVEF measurement must be completed prior to the subject being randomized.
- Subjects must have a left ventricular end diastolic dimension (LVEDD) of >2.7 cm/m2 as measured by 2-D ECHO within 12 months of the Screening Visit.
- Subjects must be on optimal conventional heart failure therapy (with the exception of a beta-blocker), including an ACEI for at least 30 days prior to the Screening Visit, or the subject must have had a trial of an ACEI and proven to be intolerant, or the subject must be taking an ARB for at least 30 days prior to the Screening Visit or proved to be intolerant. Optimal conventional therapy may also include spironolactone, digitalis glycosides, diuretics, or other vasodilators.
- Subjects must have failed the initiation, or the up-titration, of a beta-blocker drug due to hemodynamic intolerance within 12 months prior to the Screening Visit. Failure to tolerate beta-blockade for hemodynamic reasons is defined as worsening signs and symptoms of chronic heart failure, hypotension accompanied with symptoms, or evidence of organ hypoperfusion, which in the judgment of the treating physician precluded further treatment with the beta-blocker. This beta-blocker intolerance must have been documented prior to Screening, and a narrative description of the intolerance must be approved by Myogen prior to Randomization.
Who cannot join
- Subjects who meet any one of the following criteria will be deemed ineligible for participation in the study:
- Subjects with CHF due to or associated with uncorrected primary valvular disease, uncorrected thyroid disease, obstructive/hypertrophic cardiomyopathy, pericardial disease, amyloidosis, active myocarditis, malfunctioning artificial heart valve, uncorrected congenital heart disease, isolated right-sided heart failure, or primary pulmonary hypertension.
- Subjects who have undergone a cardiac revascularization, valvular surgery, or bi-ventricular resynchronization procedure within 60 days prior to the Screening Visit.
- Subjects listed for heart transplantation who are expected to be transplanted within 6 months of randomization.
- Subjects who have had a myocardial infarction within 90 days prior to the Screening Visit.
- Subjects with an ECG recorded at the Screening Visit showing any of the following: 1) evidence of transmural ischemia (dynamic ST elevation or ST elevation associated with ischemic symptoms), or 2) ventricular tachycardia (VT) or premature ventricular complexes (PVCs) associated with symptoms, or 3) VT of greater than or equal to 6 beats
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- Subjects with sustained (>15 seconds) VT, unless precipitated by an event such as an acute myocardial infarction, induction by catheter placement, or by an electrophysiology procedure, or addressed by AICD placement.
- Subjects with an AICD that has fired for any ventricular arrhythmia within 90 days of the Randomization Visit.
- Subjects with a documented diagnosis of angina that meets either of the following criteria: 1) angina diagnosed as unstable at any time within the 60 days prior to the Screening Visit or 2) angina is the primary symptom that limits daily physical activity
- Subjects who have had ventricular reduction surgery or cardiac myoplasty.
- Subjects on a mechanical assist device.
- Subjects with evidence of a concomitant disease that may interfere with the natural course of the subject's underlying heart failure for the duration of the trial.
- Subjects having a concomitant life-threatening disease for which their life expectancy is estimated to be less than one year.
- Subjects with uncontrolled insulin-dependent diabetes mellitus with a history of frequent hypoglycemic episodes or frequent hospitalizations for hyperglycemia.
- Subjects on the following concomitant medications at the time of Screening are excluded from participating in the study: 1) Calcium antagonists other than amlodipine or felodipine; 2) Flecainide, encainide, propafenone, sotalol, dofetilide or disopyramide; 3) Subjects receiving i.v. positive inotropic agents within seven days of the Screening Visit or Randomization Visit; 4) Subjects receiving a human BNP, including nesiritide, within seven days of the Screening Visit or Randomization Visit; 5) Subjects receiving oral or i.v. type-III PDE inhibitors within seven days of the Screening Visit or Randomization Visit.
- Subjects with a contraindication to treatment with a positive inotropic agent (defined as a serious adverse event attributed to previous treatment with a positive inotrope).
- Subjects with a known contraindication to beta-blocker therapy. This may include beta-agonist-dependent chronic obstructive pulmonary disease or asthma, a heart rate <55 BPM, the presence of second- or third-degree heart block without an implanted pacemaker, and first-degree heart block with a PR interval >220 milliseconds.
- Subjects with active hepatic (screening serum total bilirubin greater than or equal to 3.0 mg/dL), renal (screening serum creatinine greater than or equal to 2.0 mg/dL), hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease, which in the opinion of the Investigator, may adversely affect the safety and efficacy of the study drug or the life span of the subject.
- Subjects known to abuse or actively abusing alcohol or illicit drugs. Abuse of alcohol is defined as the usual daily intake of more than 100 grams of ethanol per day, or more than approximately 6 twelve-ounce bottles of beer, one 750 mL bottle of wine or 250 mL of 80 proof spirits.
- Subjects with a serum potassium <4.0 mEq/L or >5.5 mEq/L at Screening.
- Subjects with a serum digoxin of >1.2 ng/mL at Screening are excluded.
- Pregnant women and women at risk of becoming pregnant (i.e., not using effective methods of birth control).
- Subjects who have participated in a clinical trial involving another investigational drug or device within 30 days of the Screening Visit or at any time during the study.
- Subjects who have demonstrated noncompliance with previous medical regimens.
- Subjects who are hospitalized at the time of the Randomization Visit and are not hemodynamically stable, or for whom there is an acute cardiac or non-cardiac illness that requires further hospitalization.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Colorado
Denver, Colorado, 80262
University of Utah
Salt Lake City, Utah, 84132
About this study
Official title: A Phase III, Randomized, Double-Blind, Double Placebo-Controlled, Multicenter, Three Parallel Group Study of Enoximone Plus Extended-Release Metoprolol Succinate in Advanced CHF Subjects Previously Intolerant to Beta-Blocker Treatment
Beta-blocker medications have been shown to improve heart function and prolong the lives of patients with chronic heart failure (CHF). Some people with advanced CHF have difficulty taking beta-blocker medications due to troublesome side effects, such as low blood pressure and/or low heart rate, severe tiredness, dizziness, or shortness of breath. In other words, they have difficulty tolerating beta-blocker medications. The purpose of this study is to determine if enoximone can improve a patient's ability to tolerate a beta-blocker medication.
Read the detailed description
Over the last decade, it has become evident that certain beta-blocking agents (beta-blockers) exert a favorable effect on the natural history of mild to moderate chronic heart failure (CHF), including reducing mortality and hospitalization rate. However, as heart failure becomes more severe, beta-blockers become difficult to administer because of myocardial depression leading to hemodynamic intolerance. A recent clinical study demonstrated that subjects who could not tolerate the beta-blocker metoprolol experienced improved tolerability when low-dose, oral enoximone was administered prior to the introduction of metoprolol and during ongoing treatment. This study will investigate the hypotheses that by stabilizing subjects on enoximone first, advanced CHF subjects who are intolerant of beta-blockade will be able to 1) tolerate the effects of beta-blocker therapy, and 2) have clinical benefit that is due to the combination of both enoximone and extended-release metoprolol succinate (ER metoprolol). Support for these hypotheses will be sought by demonstrating that, as compared to placebo, low-dose, oral enoximone plus ER metoprolol will increase left ventricular ejection fraction (LVEF), improve symptoms of heart failure, and improve submaximal exercise tolerance in subjects with CHF.
- Conditions
- Heart Failure, Congestive
- Being tested
- Enoximone, Metoprolol succinate, Placebo to match enoximone, Placebo to match metoprolol succinate
- Keywords
- positive inotrope, enoximone, beta-blocker, intolerant
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnoximoneDrug
Enoximone administered orally
Metoprolol succinateDrug
Metoprolol succinate administered orally
Placebo to match enoximoneDrug
Placebo to match match enoximone administered orally
Placebo to match metoprolol succinateDrug
Placebo to match metoprolol succinate administered orally
| Study group | Role | What they receive |
|---|---|---|
| active enoximone plus active ER metoprolol | Experimental | Not described Receives: Drug: Enoximone; Drug: Metoprolol succinate |
| placebo enoximone plus active ER metoprolol | Active comparator | Not described Receives: Drug: Metoprolol succinate; Drug: Placebo to match enoximone |
| placebo enoximone plus placebo ER metoprolol | Placebo comparator | Not described Receives: Drug: Placebo to match enoximone; Drug: Placebo to match metoprolol succinate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants experiencing improved metoprolol tolerability when coadministered with enoximone
Improved tolerability measured by increased left ventricular ejection fraction (LVEF), improvement of heart failure symptoms, and improvement in submaximal exercise tolerance.
Measured: Baseline to Week 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2004 (estimated)
- Study startJul 2003
- Primary completionJun 2005
- Study completionJun 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure, CongestiveStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 175 participants
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00077948
- Sponsor's protocol ID
- EMPOWER (Protocol My-023)
- Status last verified
- Jan 2014
- First submitted
- 13 Feb 2004
- Last updated
- 10 Jan 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Double-Blind, Double Placebo-Controlled, Multicenter, Three Parallel Group Study of Enoximone Plus Extended-Release Metoprolol Succinate in Advanced CHF Subjects Previously Intolerant to Beta-Blocker Treatment
- ClinicalTrials.gov ID
- NCT00077948
- Acronym / sponsor ID
- EMPOWER (Protocol My-023)
- Conditions
- Heart Failure, Congestive
- Keywords
- positive inotrope, enoximone, beta-blocker, intolerant
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 175 participants
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Study start
- Jul 2003
- Primary completion
- Jun 2005 (actual)
- Study completion
- Jun 2005 (actual)
- First posted
- 18 Feb 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Beta-blocker medications have been shown to improve heart function and prolong the lives of patients with chronic heart failure (CHF). Some people with advanced CHF have difficulty taking beta-blocker medications due to troublesome side effects, such as low blood pressure and/or low heart rate, severe tiredness, dizziness, or shortness of breath. In other words, they have difficulty tolerating beta-blocker medications. The purpose of this study is to determine if enoximone can improve a patient's ability to tolerate a beta-blocker medication.
Detailed description
Over the last decade, it has become evident that certain beta-blocking agents (beta-blockers) exert a favorable effect on the natural history of mild to moderate chronic heart failure (CHF), including reducing mortality and hospitalization rate. However, as heart failure becomes more severe, beta-blockers become difficult to administer because of myocardial depression leading to hemodynamic intolerance. A recent clinical study demonstrated that subjects who could not tolerate the beta-blocker metoprolol experienced improved tolerability when low-dose, oral enoximone was administered prior to the introduction of metoprolol and during ongoing treatment. This study will investigate the hypotheses that by stabilizing subjects on enoximone first, advanced CHF subjects who are intolerant of beta-blockade will be able to 1) tolerate the effects of beta-blocker therapy, and 2) have clinical benefit that is due to the combination of both enoximone and extended-release metoprolol succinate (ER metoprolol). Support for these hypotheses will be sought by demonstrating that, as compared to placebo, low-dose, oral enoximone plus ER metoprolol will increase left ventricular ejection fraction (LVEF), improve symptoms of heart failure, and improve submaximal exercise tolerance in subjects with CHF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| active enoximone plus active ER metoprolol | Experimental | Drug: Enoximone, Drug: Metoprolol succinate |
| placebo enoximone plus active ER metoprolol | Active comparator | Drug: Metoprolol succinate, Drug: Placebo to match enoximone |
| placebo enoximone plus placebo ER metoprolol | Placebo comparator | Drug: Placebo to match enoximone, Drug: Placebo to match metoprolol succinate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- In order to be considered an eligible subject, all of the following entry criteria must be met:
- Subjects must be competent to provide informed written consent. Subjects must sign an IRB/IEC approved informed consent form prior to the initiation of any study procedures.
- Subjects must be 18 years of age or older.
- Subjects must have ischemic or nonischemic cardiomyopathy with symptoms of NYHA Class III or IV chronic heart failure.
- Subjects must have a LVEF of less than or equal to 35%, measured within 60 days of the Screening Visit. LVEF must be assessed by radionuclide ventriculography (MUGA). If the subject has experienced any cardiovascular events, has undergone any interventions, or received any changes in treatment that may have affected LV function since the most recent EF measurement, an LVEF measurement must be completed prior to the subject being randomized.
Key exclusion criteria (25 listed)
- Subjects who meet any one of the following criteria will be deemed ineligible for participation in the study:
- Subjects with CHF due to or associated with uncorrected primary valvular disease, uncorrected thyroid disease, obstructive/hypertrophic cardiomyopathy, pericardial disease, amyloidosis, active myocarditis, malfunctioning artificial heart valve, uncorrected congenital heart disease, isolated right-sided heart failure, or primary pulmonary hypertension.
- Subjects who have undergone a cardiac revascularization, valvular surgery, or bi-ventricular resynchronization procedure within 60 days prior to the Screening Visit.
- Subjects listed for heart transplantation who are expected to be transplanted within 6 months of randomization.
- Subjects who have had a myocardial infarction within 90 days prior to the Screening Visit.
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 |
|---|---|---|
| EnoximoneEnoximone administered orally | Drug | active enoximone plus active ER metoprolol |
| Metoprolol succinateMetoprolol succinate administered orally | Drug | active enoximone plus active ER metoprolol, placebo enoximone plus active ER metoprolol |
| Placebo to match enoximonePlacebo to match match enoximone administered orally | Drug | placebo enoximone plus active ER metoprolol, placebo enoximone plus placebo ER metoprolol |
| Placebo to match metoprolol succinatePlacebo to match metoprolol succinate administered orally | Drug | placebo enoximone plus placebo ER metoprolol |
Primary outcome
Proportion of participants experiencing improved metoprolol tolerability when coadministered with enoximone
Time frame: Baseline to Week 36
Improved tolerability measured by increased left ventricular ejection fraction (LVEF), improvement of heart failure symptoms, and improvement in submaximal exercise tolerance.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2014.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enoximone and Metoprolol succinate in people with Heart Failure, Congestive, run by Gilead Sciences at 2 sites 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 8 inclusion and 25 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: stopped early, as of the sponsor's last update on 10 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
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?
Proportion of participants experiencing improved metoprolol tolerability when coadministered with enoximone (time frame: Baseline to Week 36). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jan 2014.