Heart Failure, CongestivePhase 4NCT00233480
Statin Therapy in Heart Failure: Potential Mechanisms of Benefit
A Phase 4 study testing atorvastatin in people with Heart Failure, Congestive, run by University of California, Los Angeles at 1 site in United States.
Trial summary
The goal of the investigators' study is to further understand the potentially beneficial effects of statin therapy in patients with heart failure. It is hypothesized that statins will 1) increase the heart's pumping ability 2) improve functioning of the sympathetic nervous system and 3) decrease immune activation in… 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?
- atorvastatin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2005to Feb 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age≥18 years old
- LVEF ≤ 35%, as documented by echocardiography, radionuclide ventriculography, gated SPECT, or contrast ventriculography within past 6 months
- Symptomatic HF (NYHA II-IV) or current NYHA I with history of symptomatic HF within the last year
- Stable doses of optimal HF medical therapy, unless documented contraindication.
Who cannot join
- Ischemic etiology of HF, defined as the presence of at least one of the following four criteria; angiographic evidence of > 50% lesion in 1 or more of the 3 major epicardial vessels; history of myocardial infarction; history of revascularization procedure; evidence of significant perfusion defect in the setting of ischemic symptoms.
- Clinical indication for statin treatment - coronary artery, cerebrovascular, or peripheral vascular disease
- Major cardiovascular event or surgical procedure within past 8 weeks
- LDL<70 mg/dL
- HF secondary to congenital heart disease or uncorrected valvular disease
- Treatment with statin within past 2 months
Show all 10Show fewer
- Pregnancy
- Contraindication to statin: moderate liver disease, AST/ALT > 150 U/ L, known hypersensitivity
- Likely to receive heart transplant within 3 months
- Known peripheral or autonomic neuropathy
Trial locations and contacts
1 site in 1 country.
United States1 site
Ahmanson-UCLA Cardiomyopathy Center
Los Angeles, California, 90095
About this study
Official title: A Double-blind Randomized, Placebo-Controlled, Single-Center Study to Assess the Impact of Statins on the Autonomic Nervous System and Cardiac Structure/Function in Non-Ischemic Heart Failure
The goal of the investigators' study is to further understand the potentially beneficial effects of statin therapy in patients with heart failure. It is hypothesized that statins will 1) increase the heart's pumping ability 2) improve functioning of the sympathetic nervous system and 3) decrease immune activation in heart failure.
Read the detailed description
Recent evidence suggests that HMG-Coenzyme A (statin) therapy may be associated with improved survival in both ischemic and non-ischemic heart failure (HF). Large, randomized outcome studies of statins in HF are currently underway, but these trials will not address underlying mechanisms. The aim of the study is to investigate statins' potentially beneficial mechanisms of action in HF, focusing on: 1) sympathetic nervous system activation and 2) myocardial remodeling, and 3) immune activation in heart failure.
Fifty patients with systolic HF of non-ischemic etiology from a single center will be randomized in a double-blinded fashion to 3 months of atorvastatin 10mg QD (25 subjects) vs matching placebo QD (25 subjects). The following exams will be performed at baseline (pre-treatment) and at end of study (post-treatment): sympathetic microneurography, echocardiography, and peripheral blood chemokine analysis. Sympathetic microneurography at the peroneal nerve will directly quantify changes in sympathetic nerve activity (bursts/minute). Echocardiography (with the addition of MRI in a subset of subjects without pacemakers or implantable defibrillators) will be used to track changes in cardiac structure and function; indices of remodeling will include measurement of left ventricular mass index, left ventricular volume indices, left ventricular ejection fraction, and subendocardial scar quantification (MRI only). Immune activation will be characterized by circulating cytokines and chemokines. Additionally, quantification of established cardiac biomarkers (cardiac troponin, B-type natriuretic peptide, and C-reactive Protein), Holter monitor/heart rate variability studies, and quality of life and global clinical assessment will be performed pre- and post- treatment.
Neither sympathetic microneurography nor MRI have been previously utilized to assess statins' effects in humans with HF. The impact of statin therapy on inflammatory chemokine activation in HF also has not been studied. The knowledge gained from our proposed investigations may serve as a basis for understanding how statin therapy has potential to improve clinical outcomes in HF, and may ultimately lead to new therapeutic strategies for HF.
- Conditions
- Heart Failure, Congestive
- Being tested
- atorvastatin, placebo
- Keywords
- Randomized Controlled Trial, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Sympathetic Nervous System, Ventricular Remodeling, Chemokines
- Medical subject headings
- Heart Failure, Ventricular Remodeling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atorvastatinDrug
Also called lipitor
atorvastatin 10mg PO QD
placeboDrug
matched placebo Qd x 3 months
| Study group | Role | What they receive |
|---|---|---|
| active treatment | Experimental | atorvastatin 10mg QD x 3 months Receives: Drug: atorvastatin |
| placebo | Placebo comparator | matched placebo QD x 3 months Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
LVEF (Left Ventricular Ejection Fraction)
Left ventricular ejection fraction was assessed by transthoracic echocardiography according to Simpson's rule (biplane method of disks).
Measured: baseline and three months
Muscle Sympathetic Nerve Activity (by Sympathetic Microneurography)
Measured: Baseline and three months
Secondary outcomes (4)
Left Ventricular End-diastolic Dimension (LVEDD)
The end-diastolic dimension of the left ventricle (in mm) was measured with 2D echocardiography performed by experienced technicians using Acuson Sequoia Echocardiography System
Measured: Baseline and three months
Cardiac Biomarker Level BNP
B-type natriuretic peptide, measured pg/mL at baseline and post-treatment
Measured: Baseline, 3 months
High-sensitivity C-reactive Protein (hsCRP) as a Cardiac Biomarker
Measured: Baseline, Three months
Cardiac Troponin I (cTnI)
Participants with cTnI ≥0.04 ng/mL
Measured: Baseline, Three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2005 (estimated)
- Study startAug 2005
- Primary completionFeb 2009
- Study completionFeb 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 (4)Papers the sponsor has linked to this study.
- Other trials for Heart Failure, CongestiveStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Tamara Horwich, University of California, Los Angeles
- Investigators
- Tamara B Horwich, MD, Principal investigator, UCLA Division of Cardiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00233480
- Sponsor's protocol ID
- UCLA IRB #04-12-007-01
- Other IDs
- 1K23HL085097-01A1
- Status last verified
- Mar 2020
- First submitted
- 4 Oct 2005
- Last updated
- 20 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Horwich TB, Middlekauff HR. Potential autonomic nervous system effects of statins in heart failure. Heart Fail Clin. 2008 Apr;4(2):163-70. doi: 10.1016/j.hfc.2008.01.004.
PubMed 18433696Horwich TB, MacLellan WR. Atorvastatin and statins in the treatment of heart failure. Expert Opin Pharmacother. 2007 Dec;8(17):3061-8. doi: 10.1517/14656566.8.17.3061.
PubMed 18001265PubMed ID 22041323
Horwich TB, Middlekauff HR, Maclellan WR, Fonarow GC. Statins do not significantly affect muscle sympathetic nerve activity in humans with nonischemic heart failure: a double-blind placebo-controlled trial. J Card Fail. 2011 Nov;17(11):879-86. doi: 10.1016/j.cardfail.2011.07.008. Epub 2011 Sep 3.
PubMed 22041323
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind Randomized, Placebo-Controlled, Single-Center Study to Assess the Impact of Statins on the Autonomic Nervous System and Cardiac Structure/Function in Non-Ischemic Heart Failure
- ClinicalTrials.gov ID
- NCT00233480
- Acronym / sponsor ID
- UCLA IRB #04-12-007-01
- Conditions
- Heart Failure, Congestive
- Keywords
- Randomized Controlled Trial, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Sympathetic Nervous System, Ventricular Remodeling, Chemokines
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- Pfizer, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Aug 2005
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 5 Oct 2005 (estimated)
- Results
- Posted 20 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of the investigators' study is to further understand the potentially beneficial effects of statin therapy in patients with heart failure. It is hypothesized that statins will 1) increase the heart's pumping ability 2) improve functioning of the sympathetic nervous system and 3) decrease immune activation in heart failure.
Detailed description
Recent evidence suggests that HMG-Coenzyme A (statin) therapy may be associated with improved survival in both ischemic and non-ischemic heart failure (HF). Large, randomized outcome studies of statins in HF are currently underway, but these trials will not address underlying mechanisms. The aim of the study is to investigate statins' potentially beneficial mechanisms of action in HF, focusing on: 1) sympathetic nervous system activation and 2) myocardial remodeling, and 3) immune activation in heart failure.
Fifty patients with systolic HF of non-ischemic etiology from a single center will be randomized in a double-blinded fashion to 3 months of atorvastatin 10mg QD (25 subjects) vs matching placebo QD (25 subjects). The following exams will be performed at baseline (pre-treatment) and at end of study (post-treatment): sympathetic microneurography, echocardiography, and peripheral blood chemokine analysis. Sympathetic microneurography at the peroneal nerve will directly quantify changes in sympathetic nerve activity (bursts/minute). Echocardiography (with the addition of MRI in a subset of subjects without pacemakers or implantable defibrillators) will be used to track changes in cardiac structure and function; indices of remodeling will include measurement of left ventricular mass index, left ventricular volume indices, left ventricular ejection fraction, and subendocardial scar quantification (MRI only). Immune activation will be characterized by circulating cytokines and chemokines. Additionally, quantification of established cardiac biomarkers (cardiac troponin, B-type natriuretic peptide, and C-reactive Protein), Holter monitor/heart rate variability studies, and quality of life and global clinical assessment will be performed pre- and post- treatment.
Neither sympathetic microneurography nor MRI have been previously utilized to assess statins' effects in humans with HF. The impact of statin therapy on inflammatory chemokine activation in HF also has not been studied. The knowledge gained from our proposed investigations may serve as a basis for understanding how statin therapy has potential to improve clinical outcomes in HF, and may ultimately lead to new therapeutic strategies for HF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| active treatment | Experimental | Drug: atorvastatinatorvastatin 10mg QD x 3 months |
| placebo | Placebo comparator | Drug: placebomatched placebo QD x 3 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age≥18 years old
- LVEF ≤ 35%, as documented by echocardiography, radionuclide ventriculography, gated SPECT, or contrast ventriculography within past 6 months
- Symptomatic HF (NYHA II-IV) or current NYHA I with history of symptomatic HF within the last year
- Stable doses of optimal HF medical therapy, unless documented contraindication.
Key exclusion criteria (10 listed)
- Ischemic etiology of HF, defined as the presence of at least one of the following four criteria; angiographic evidence of > 50% lesion in 1 or more of the 3 major epicardial vessels; history of myocardial infarction; history of revascularization procedure; evidence of significant perfusion defect in the setting of ischemic symptoms.
- Clinical indication for statin treatment - coronary artery, cerebrovascular, or peripheral vascular disease
- Major cardiovascular event or surgical procedure within past 8 weeks
- LDL<70 mg/dL
- HF secondary to congenital heart disease or uncorrected valvular disease
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 |
|---|---|---|
| atorvastatinAlso: lipitoratorvastatin 10mg PO QD | Drug | active treatment |
| placebomatched placebo Qd x 3 months | Drug | placebo |
Primary outcome
LVEF (Left Ventricular Ejection Fraction)
Time frame: baseline and three months
Left ventricular ejection fraction was assessed by transthoracic echocardiography according to Simpson's rule (biplane method of disks).
Muscle Sympathetic Nerve Activity (by Sympathetic Microneurography)
Time frame: Baseline and three months
4 secondary outcomes
Left Ventricular End-diastolic Dimension (LVEDD)
Time frame: Baseline and three months
Cardiac Biomarker Level BNP
Time frame: Baseline, 3 months
High-sensitivity C-reactive Protein (hsCRP) as a Cardiac Biomarker
Time frame: Baseline, Three months
Cardiac Troponin I (cTnI)
Time frame: Baseline, Three months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18433696Horwich TB, Middlekauff HR. Potential autonomic nervous system effects of statins in heart failure. Heart Fail Clin. 2008 Apr;4(2):163-70. doi: 10.1016/j.hfc.2008.01.004.
- Background: PubMed 18001265Horwich TB, MacLellan WR. Atorvastatin and statins in the treatment of heart failure. Expert Opin Pharmacother. 2007 Dec;8(17):3061-8. doi: 10.1517/14656566.8.17.3061.
- Results publicationPubMed ID 22041323
- Derived from this study: PubMed 22041323Horwich TB, Middlekauff HR, Maclellan WR, Fonarow GC. Statins do not significantly affect muscle sympathetic nerve activity in humans with nonischemic heart failure: a double-blind placebo-controlled trial. J Card Fail. 2011 Nov;17(11):879-86. doi: 10.1016/j.cardfail.2011.07.008. Epub 2011 Sep 3.
Related trials for Heart Failure, Congestive
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
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.
Tamara B Horwich, MD principal investigator
UCLA Division of Cardiology
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 atorvastatin in people with Heart Failure, Congestive, run by University of California, Los Angeles 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 4 inclusion and 10 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 20 Mar 2020. 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. 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 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 20 Mar 2020). 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?
LVEF (Left Ventricular Ejection Fraction) (time frame: baseline and three months). The study lists 2 primary outcomes in all. 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 NCT00233480, which also lists 4 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 20 Mar 2020.