Polypharmacy in the Heart Failure Patient: Are All Prescribed Drug Classes Required? Statin Withdrawal Study
Primary Purpose
Heart Failure
Status
Completed
Phase
Not Applicable
Locations
Australia
Study Type
Interventional
Intervention
Withdrawal of statin therapy
Statin therapy
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Heart Failure, Statin withdrawal
Eligibility Criteria
Inclusion Criteria:
- Over the age of 18 years
- Documented heart failure of ischaemic, idiopathic or hypertensive cause
- New York Heart Association (NYHA) class II, III or IV symptoms
- LVEF < 0.40, or no more than 0.35 if NYHA class II and ischaemic aetiology.
- Receiving ACE inhibitor or ARB (Angiotensin II Receptor Blockers), β-blocker and diuretic therapy at the optimal doses.
- Has been receiving statin therapy for at least 3 months
- Willing and able to provide informed consent
Exclusion Criteria:
- Treatment with statins primarily for treatment of hypercholesterolaemia
- Obstructive or restrictive cardiomyopathy
- Uncorrected primary valvular disease
- Active myocarditis
- Decompensated heart failure or a need for inotropic therapy
- Myocardial infarction within the past 6 months
- Unstable angina or stroke within the past 3 months
- PCI (Percutaneous coronary intervention), CABG (coronary artery bypass graft)or implantation of cardioverter-defibrillator or biventricular pacemaker within the past 3 months or a planned implantation of such a device
- Previous or planned cardiac transplantation
- Pericardial disease or systemic disease (eg amyloidosis)
- Acute or chronic liver disease
- Alanine and aspartate transminase concentrations more than 1.5 times the upper limit of normal
- Chronic muscle disease or an unexplained creatinine kinase level of more than 2.5 times the upper limit of normal
- Serum creatinine level greater than 221 micromol/L
- Previous treatment with cyclosporine
- Exercise capacity limited by factors other than cardiac dyspnoea
- Hospitalisation within one month of randomisation
- Pregnant or lactating women or women of childbearing potential who were not adequately protected against becoming pregnant
- Any other concurrent condition that, in the opinion of the investigator, would prevent completion of the clinical trial
Sites / Locations
- Clinical Pharmacology, Alfred Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Statin withdrawal
Stable statin therapy
Arm Description
Participants will received a placebo for 12 weeks.
Participants need to have been receiving statin therapy for at least 3 months and be on a stable dose.
Outcomes
Primary Outcome Measures
NYHA (New York Heart Association) Heart Failure class
Secondary Outcome Measures
6 minutes walk test
Quality of life questionnaire
Change in BNP (Brain natriuretic peptide)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01554592
Brief Title
Polypharmacy in the Heart Failure Patient: Are All Prescribed Drug Classes Required? Statin Withdrawal Study
Official Title
Polypharmacy in the Heart Failure Patient: Are All Prescribed Drug Classes Required? Statin Withdrawal Study.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Alfred
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Heart failure (cardiomyopathy) is a chronic condition in which the heart fails to function as a pump to move blood around the body. This sets up a complex physiologic response to compensate, which include activation of many hormonal mechanisms which result in fluid accumulation.
In recent years, medications to block the hormonal response to heart failure are given as standard drugs, and these include ACE inhibitors and beta blockers. Mortality is reduced with these medications, as well as symptoms improved. Other medications are also used in heart failure, for which a clear-cut benefit has not been demonstrated. Statins, also called HMG CoA reductase inhibitors, are used to reduce cholesterol levels and can help to prevent heart failure by preventing heart attacks. They have been used in heart failure that is not caused by heart attacks in the belief that they had "pleiotropic" effects, meaning that they had beneficial effects in heart failure separate from the reduction in cholesterol.
However large trials in heart failure have demonstrated that statins do not increase survival compared with placebo. There is no evidence to recommend their routine use in established heart failure caused by either heart attacks or genetics.
The investigators propose that the use of statins in heart failure is unnecessary and could be stopped. The importance of finding evidence to cease unproven medications in heart failure cannot be understated. Patients with heart failure take an average of six prescription medications each day. Each medication has side effects and the interactions of all the drugs together are unknown. Statins are the commonest reason for side effects in patients with heart failure, causing muscle pains and gastrointestinal upset.
In this study, the investigators plan to withdraw statins from patients with stable heart failure in a closely monitored environment and watch for the effect of this on heart failure and on how they feel generally.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Heart Failure, Statin withdrawal
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Statin withdrawal
Arm Type
Experimental
Arm Description
Participants will received a placebo for 12 weeks.
Arm Title
Stable statin therapy
Arm Type
Active Comparator
Arm Description
Participants need to have been receiving statin therapy for at least 3 months and be on a stable dose.
Intervention Type
Drug
Intervention Name(s)
Withdrawal of statin therapy
Intervention Description
Participants currently received statin therapy will have their statin stopped for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Statin therapy
Intervention Description
Participants will continue on stable statin therapy.
Primary Outcome Measure Information:
Title
NYHA (New York Heart Association) Heart Failure class
Time Frame
baseline and after 12 weeks of treatemnt
Secondary Outcome Measure Information:
Title
6 minutes walk test
Time Frame
Baseline and after 12 weeks of treatment
Title
Quality of life questionnaire
Time Frame
Baseline and after 12 weeks of treatment
Title
Change in BNP (Brain natriuretic peptide)
Time Frame
Baseline and after 12 weeks of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Over the age of 18 years
Documented heart failure of ischaemic, idiopathic or hypertensive cause
New York Heart Association (NYHA) class II, III or IV symptoms
LVEF < 0.40, or no more than 0.35 if NYHA class II and ischaemic aetiology.
Receiving ACE inhibitor or ARB (Angiotensin II Receptor Blockers), β-blocker and diuretic therapy at the optimal doses.
Has been receiving statin therapy for at least 3 months
Willing and able to provide informed consent
Exclusion Criteria:
Treatment with statins primarily for treatment of hypercholesterolaemia
Obstructive or restrictive cardiomyopathy
Uncorrected primary valvular disease
Active myocarditis
Decompensated heart failure or a need for inotropic therapy
Myocardial infarction within the past 6 months
Unstable angina or stroke within the past 3 months
PCI (Percutaneous coronary intervention), CABG (coronary artery bypass graft)or implantation of cardioverter-defibrillator or biventricular pacemaker within the past 3 months or a planned implantation of such a device
Previous or planned cardiac transplantation
Pericardial disease or systemic disease (eg amyloidosis)
Acute or chronic liver disease
Alanine and aspartate transminase concentrations more than 1.5 times the upper limit of normal
Chronic muscle disease or an unexplained creatinine kinase level of more than 2.5 times the upper limit of normal
Serum creatinine level greater than 221 micromol/L
Previous treatment with cyclosporine
Exercise capacity limited by factors other than cardiac dyspnoea
Hospitalisation within one month of randomisation
Pregnant or lactating women or women of childbearing potential who were not adequately protected against becoming pregnant
Any other concurrent condition that, in the opinion of the investigator, would prevent completion of the clinical trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henry Krum, MBBS FRACP PhD
Organizational Affiliation
Alfred Hospital/Monash University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Pharmacology, Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
12. IPD Sharing Statement
Learn more about this trial
Polypharmacy in the Heart Failure Patient: Are All Prescribed Drug Classes Required? Statin Withdrawal Study
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