Effects of Pentoxiphylline on Left Ventricular (LV) Systolic Function Indices and Circulating Biomarkers in Patients With Chronic Congestive Heart Failure (CHF)

Study Overview
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Brief Summary
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This is a prospective, double blinded randomized clinical study to evaluate the Effects of Pentoxifylline on left ventricular systolic function indices and circulating biomarkers in patients with chronic congestive heart failure. A few studies all focused in Africa have consistently shown marked beneficial effects of pentoxifylline in improvement of left ventricular size and systolic function along with marked decrease in biomarkers of heart failure and apoptosis markers on top of standard CHF therapy. Furthermore pentoxifylline was shown to have negligible effects on heart rate, blood pressure in those studies. Limitations of these studies are that they are largely single center originating in the African subcontinent and have never been tested in the North American population, particularly Caucasians. Despite major advances in medical therapy for congestive heart failure, it is still one of the leading causes of morbidity and mortality in North America. Most medications tested for improvement of Ejection Fraction with the exception of Beta-Blockers and Ace-Inhibitors have been associated with worsening mortality. Pentoxifylline is a medication that has negligible effects on myocardial oxygen consumption, yet promising effects on inflammatory markers seen in CHF with the possibility of improvement in LV systolic function and symptomology and may prove to be a useful addition for CHF patients. This would prove to be especially useful, particularly when associated with no major side effects.

Detailed Description
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Patients who meet inclusion criteria will have a baseline physical exam, Heart Failure status assessment based on the Kansas City Heart Failure Questionnaire, EF assessment based on SPECT MUGA, cardiopulmonary exam to evaluate Vo2 max and assessment of left ventricular end diastolic and systolic dimensions based on 2D echo and labs drawn to assess circulating biomarkers. Patients will than be randomized into the control population where they will receive a placebo medication vs. the study population who will receive pentoxiphylline 400mg three times daily for 6 months. Patients will also have a one and three month clinic visit to assess for any potential change in symptoms and to assess medication compliance. Patients will then have a 6 month follow-up with repeat physical exam, Heart Failure status assessment based on the Kansas City Heart Failure Questionnaire, EF assessment based on SPECT MUGA, cardiopulmonary exam to assess Vo2 Max and assessment of left ventricular end diastolic and systolic dimensions based on 2D echo and labs drawn to assess circulating biomarkers.

Official Title
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Effects of Pentoxiphylline on Left Ventricular Systolic Function Indices and Circulating Biomarkers in Patients With Chronic Congestive Heart Failure.

Conditions
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Congestive Heart Failure

Intervention / Treatment
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* Drug: Placebo
* Drug: Pentoxifylline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-ischemic and ischemic class II-III heart failure patients on maximally tolerated evidence based medications. (i.e. BB (coreg, toprol, bisoprolol), ACEI/ARBS, Diuretics, +/- aldactone, digoxin). Patients should also have an expected survival of greater than 6 months, including all other co-morbidities. Sinus Rhythm Age >18 LVEF <40% as assessed by (SPECT MUGA, ECHO). Exclusion Criteria: Class I and Class IV heart failure patients, patients who are newly diagnosed and currently are not on traditional evidence based medications. Patients who have BiV-ICD placement. Patients who decompensate into class IV heart failure during the study period requiring inotropes, LVAD, upgrade to BiV-ICD, will be reported on for potential treatment failure but will be taken out of the study. Patients whose clinical conditions other than cardiomyopathy could influence inflammatory biomarkers. (i.e. Connective Tissue disorders, HIV) Pregnancy Severe exercise induced malignant ventricular arrhythmia Any systemic process other than cardiomyopathy that would lead to survival <6 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sugar Pill<br>Placebo control Group with sugar pill three times daily for 6 months | Drug: Placebo<br>* Sugar Pill 400mg taken orally three times a day for 6 months<br>|
| Experimental: Pentoxifylline<br>Pentoxifylline 400mg tablets to be taken three times daily for 6 months | Drug: Pentoxifylline<br>* Pentoxifylline 400mg taken orally Three times a day for 6 months<br>* Other names: Trental;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in Left Ventricular Ejection Fraction > 5% | Improvement in Left Ventricular Ejection Fraction > 5% (i.e: 20 to 25%) measured by SPECT MUGA after 6 months of pentoxifylline use. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular End Systolic Volume Index | Improvement in Left Ventricular End Systolic Volume Index (decrease of 10%) as measured by 2D echo | 6 months | 
| Left Ventricular End Diastolic Volume Index | Improvement in Left Ventricular End Diastolic Volume Index (decrease of 10%) as measured by 2D echo | 6 Months | 
| Quality of Life Improvement | Improvement in Quality of Life as Quantified by the Kansas City Heart Failure Questionaire. | 6 Months | 
| Circulating Inflammatory Biomarkers | Improvement in Circulating Inflammatory Biomarkers (e.g. TNF, IL6). | 6 Months | 
| Change in VO2 Max | Change in VO2 max over the study period. (With a change of 1 ml/kg/min as measured by cardiopulmonary exam considered meaningful.) | 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Congestive Heart Failure, Left Systolic Function, Biomarkers, Pentoxifylline