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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Henry Ford Health System
Sponsor:
Information provided by (Responsible Party):
Karthikeyan Ananthasubramaniam, Henry Ford Health System
ClinicalTrials.gov Identifier:
NCT01337349
First received: April 15, 2011
Last updated: August 27, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention
Congestive Heart Failure
Drug: Placebo
Drug: Pentoxifylline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Pentoxiphylline on Left Ventricular Systolic Function Indices and Circulating Biomarkers in Patients With Chronic Congestive Heart Failure.

Resource links provided by NLM:


Further study details as provided by Henry Ford Health System:

Primary Outcome Measures:
  • Improvement in Left Ventricular Ejection Fraction > 5% [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Improvement in Left Ventricular Ejection Fraction > 5% (i.e: 20 to 25%) measured by SPECT MUGA after 6 months of pentoxifylline use.


Secondary Outcome Measures:
  • Left Ventricular End Systolic Volume Index [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Improvement in Left Ventricular End Systolic Volume Index (decrease of 10%) as measured by 2D echo

  • Left Ventricular End Diastolic Volume Index [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    Improvement in Left Ventricular End Diastolic Volume Index (decrease of 10%) as measured by 2D echo

  • Quality of Life Improvement [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    Improvement in Quality of Life as Quantified by the Kansas City Heart Failure Questionaire.

  • Circulating Inflammatory Biomarkers [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]
    Improvement in Circulating Inflammatory Biomarkers (e.g. TNF, IL6).

  • Change in VO2 Max [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    Change in VO2 max over the study period. (With a change of 1 ml/kg/min as measured by cardiopulmonary exam considered meaningful.)


Estimated Enrollment: 45
Study Start Date: July 2010
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Sugar Pill
Placebo control Group with sugar pill three times daily for 6 months
Drug: Placebo
Sugar Pill 400mg taken orally three times a day for 6 months
Experimental: Pentoxifylline
Pentoxifylline 400mg tablets to be taken three times daily for 6 months
Drug: Pentoxifylline
Pentoxifylline 400mg taken orally Three times a day for 6 months
Other Name: Trental

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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).
  2. Patients should also have an expected survival of greater than 6 months, including all other co-morbidities.
  3. Sinus Rhythm
  4. Age >18
  5. LVEF <40% as assessed by (SPECT MUGA, ECHO).

Exclusion Criteria:

  1. Class I and Class IV heart failure patients, patients who are newly diagnosed and currently are not on traditional evidence based medications.
  2. Patients who have BiV-ICD placement.
  3. 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.
  4. Patients whose clinical conditions other than cardiomyopathy could influence inflammatory biomarkers. (i.e. Connective Tissue disorders, HIV)
  5. Pregnancy
  6. Severe exercise induced malignant ventricular arrhythmia
  7. Any systemic process other than cardiomyopathy that would lead to survival <6 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01337349

Contacts
Contact: Karthikeyan Ananthasubramaniam, MD 313-916-2721 kananth1@hfhs.org
Contact: Prasanth Lingam, MD 313-916-2721 plingam1@hfhs.org

Locations
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Karthikeyan Ananthasubramaniam, MD    313-916-2721    kananth1@hfhs.org   
Contact: Prasanth Lingam, MD    313-916-2721    plingam1@hfhs.org   
Principal Investigator: Karthikeyan Ananthasubramaniam, MD         
Sub-Investigator: Prasanth Lingam, MD         
Sponsors and Collaborators
Henry Ford Health System
Investigators
Principal Investigator: Karthikeyan Ananthasubramaniam, MD Henry Ford Health Systems
  More Information

No publications provided

Responsible Party: Karthikeyan Ananthasubramaniam, Director Nuclear Cardiology and Echocardiography, Henry Ford Health System
ClinicalTrials.gov Identifier: NCT01337349     History of Changes
Other Study ID Numbers: 2192010
Study First Received: April 15, 2011
Last Updated: August 27, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Henry Ford Health System:
Pentoxifylline
Chronic Congestive Heart Failure
Left Systolic Function
Biomarkers

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Pentoxifylline
Antioxidants
Cardiovascular Agents
Enzyme Inhibitors
Free Radical Scavengers
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Protective Agents
Radiation-Protective Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 21, 2014