Effects of Atorvastatin Treatment on Left Ventricular Diastolic Function in Peritoneal Dialysis Patients (ALEVENT)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01503671
First received: January 2, 2012
Last updated: January 3, 2012
Last verified: November 2011
  Purpose

Background

Heart failure is the final consequence of various heart disease and is also the leading cause of mortality worldwide. Diastolic dysfunction refers to an abnormality of diastolic distensibility, filling, or relaxation of the left ventricle. Patients with hypertensive left ventricular hypertrophy and an echocardiogram showing a normal ejection fraction and abnormal left ventricular filling can be said to have diastolic dysfunction. If pulmonary edema or effort dyspnea developed in such a patient. The term diastolic heart failure would be appropriate.

Pathology leading to diastolic heart failure include: impaired relaxation, increased passive stiffness, endocardial and pericardial disorders, microvacular flow and neurohormonal regulation. Among them, the association of pro-inflammatory system and diastolic dysfunction are already established. The investigators therefore hypothesized that the change of serum inflammatory markers might be associated with the change of left ventricular diastolic function and the investigators thus conducted a randomized case-control trial with this regard.

Method and materials

This is a case-control randomized study. The definition of left ventricular diastolic function is according to Guideline from the ACC and AHA. The investigators will evaluate left ventricular diastolic function noninvasively by echocardiography before and after the intervention. Exclusion criteria include coronary artery disease, significant valvular heart disease, cardiomyopathy, pericardial disease and renal insufficiency. The investigators would like to enroll 50 cases and the same numbers of the controls. The inclusion criteria are subjects who underwent peritoneal dialysis at the investigators hospital for more than 6 months with higher pro-inflammation serum cytokine levels (TNF-alpha > 5ng/ml and IL-6 > 5 ng/ml). Atorvastatin (40mg/day) would be given to those who were allocated to the intervention group. The investigators will than follow up cardiac diastolic function by echocardiography and also the change of serum markers. The investigators would also genotype the inflammation-associated genes and their promoter region and find the association between genetic polymorphisms and the treatment effects of statins.


Condition Intervention Phase
Heart Failure
Drug: Atorvastatin
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Atorvastatin Treatment on Left Ventricular Diastolic Function in Peritoneal Dialysis Patients (ALEVENT)

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Left ventricular diastolic function [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    We will arrange UCG follow up to delineate the change of LV diastolic function after intervention


Secondary Outcome Measures:
  • Mortality [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Total Mortality differences

  • Major cardiovascular events [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Check the MACE differences

  • Side effects [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Follow up the number of rhabdomyolyis, hepatitis


Estimated Enrollment: 100
Study Start Date: November 2011
Estimated Study Completion Date: November 2012
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvastatin
Atorvastatin 40 mg/day for high inflammation CAPD patient
Drug: Atorvastatin
Atorvastatin 40 mg/day
Other Name: Lipitor
Placebo Comparator: Placebo
Placebo arm
Drug: Placebo
Give Placebo
Other Name: Placebo

Detailed Description:

We will evaluate left ventricular diastolic function noninvasively by echocardiography before and after the intervention. Exclusion criteria include coronary artery disease, significant valvular heart disease, cardiomyopathy, pericardial disease and renal insufficiency. We would like to enroll 50 cases and the same numbers of the controls. The inclusion criteria are subjects who underwent peritoneal dialysis at our hospital for more than 6 months with higher pro-inflammation serum cytokine levels (TNF-alpha > 5ng/ml and IL-6 > 5 ng/ml). Atorvastatin (40mg/day) would be given to those who were allocated to the intervention group. We will than follow up cardiac diastolic function by echocardiography and also the change of serum markers. We would also genotype the inflammation-associated genes and their promoter region and find the association between genetic polymorphisms and the treatment effects of statins.

Patients population and Monitoring The study population will consist of patients with CAPD and DHF (NYHA Class II-IV), aged 18 years or older without reduced systolic function, defined as left ventricular EF ≤ 45%, Patients fulfilling the inclusion and exclusion criteria will be randomized in a 1:1 ratio into the study from the single medical centers.

Inclusion criteria:

  1. Outpatients ≥ 20 year of age, male or female with essential hypertension
  2. Patients must be on a stable condition of CAPD for at least 6 months.

Exclusion Criteria:

  1. History of hypersensitivity to any of the study drugs.
  2. Current acute decompensated HF (exacerbation of chronic HF manifested by signs & symptoms that may require IV therapy).
  3. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or major vascular surgery, percutaneous coronary intervention (PCI) or carotid angioplasty, within the past 3 months prior to visit 1.
  4. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 6 months after Visit 1.
  5. Right heart failure due to severe pulmonary disease.
  6. Diagnosis of peripartum or chemotherapy induced cardiomyopathy within the 12 months prior to visit 1.
  7. Patients with a history of heart transplant or who are on a transplant list or with left ventricular assistance device (LVAD device).
  8. Documented ventricular arrhythmia with syncopal episodes within past 3 months, prior to visit 1, that is untreated.
  9. Symptomatic bradycardia or second or third degree heart block without a pacemaker.
  10. Implantation of a CRT (cardiac resynchronization therapy) device within the prior 3 months from visit 1 or intent to implant a CRT device.
  11. Presence of hemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation.
  12. Presence of other hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic and sub-aortic stenosis.
  13. Severe primary pulmonary, renal or hepatic disease judged by physicians.
  14. Presence of any other disease with a life expectancy of < 1 year.
  15. Chronic long-term requirement for NSAIDs (high dose) or COX2 inhibitors, with the exception of aspirin at doses used for CV prophylaxis (≤325 mg o.d.).
  16. Subjects are now breast feeding, get pregnant or will be pregnant within 6 months.
  Eligibility

Ages Eligible for Study:   20 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Outpatients ≥ 20 year of age, male or female with essential hypertension
  2. Patients must be on a stable condition of CAPD for at least 6 months.

Exclusion Criteria:

  1. History of hypersensitivity to any of the study drugs.
  2. Current acute decompensated HF (exacerbation of chronic HF manifested by signs & symptoms that may require IV therapy).
  3. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or major vascular surgery, percutaneous coronary intervention (PCI) or carotid angioplasty, within the past 3 months prior to visit 1.
  4. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 6 months after Visit 1.
  5. Right heart failure due to severe pulmonary disease.
  6. Diagnosis of peripartum or chemotherapy induced cardiomyopathy within the 12 months prior to visit 1.
  7. Patients with a history of heart transplant or who are on a transplant list or with left ventricular assistance device (LVAD device).
  8. Documented ventricular arrhythmia with syncopal episodes within past 3 months, prior to visit 1, that is untreated.
  9. Symptomatic bradycardia or second or third degree heart block without a pacemaker.
  10. Implantation of a CRT (cardiac resynchronization therapy) device within the prior 3 months from visit 1 or intent to implant a CRT device.
  11. Presence of hemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation.
  12. Presence of other hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic and sub-aortic stenosis.
  13. Severe primary pulmonary, renal or hepatic disease judged by physicians.
  14. Presence of any other disease with a life expectancy of < 1 year.
  15. Chronic long-term requirement for NSAIDs (high dose) or COX2 inhibitors, with the exception of aspirin at doses used for CV prophylaxis (≤325 mg o.d.).
  16. Subjects are now breast feeding, get pregnant or will be pregnant within 6 months.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01503671

Contacts
Contact: Cho-Kai Wu, MD 886-23123456 ext 62152 chokaiwu@yahoo.com.tw

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Cho-Kai Wu, MD    886-23123456 ext 62152    chokaiwu@yahoo.com.tw   
Principal Investigator: Cho-Kai Wu, MD         
Sub-Investigator: Jenq-Wen Huang, MD         
Sub-Investigator: Chia-Ti Tsai, MD, PhD         
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Study Chair: Cho-Kai Wu, MD National Taiwan University Hospital
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01503671     History of Changes
Other Study ID Numbers: 201108035MD
Study First Received: January 2, 2012
Last Updated: January 3, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
left ventricular diastolic function
inflammation
peritoneal dialysis
LV diastolic function changes after statin intervention

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014