Cilostazol for HFpEF

Cilostazol for HFpEF (Heart Failure With a Preserved Ejection Fraction)

Determine if cilostazol improves symptoms and NTproBNP levels (heart failure blood marker) in heart failure with preserved ejection fraction (HFpEF) - a prevalent syndrome without targeted evidence-based treatment.

This will be assessed in a prospective 1-month single blinded study with 2 cross-overs n-of-1 study design with placebo and cilostazol

Study Overview

• Status: Completed
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: Placebo; Drug: Cilostazol 100Mg Tab

Detailed Description

Heart failure (HF) is the #1 reason for hospital admissions. About half of the patients with HF have a preserved ejection fraction (HFpEF). There is no targeted evidence-based treatment for HFpEF. We recently reported that elevating the heart rate with pacemakers conveys clinical benefits e.g. reduction in heart failure symptoms, lowering filling pressures and an increase in walk distance. Cilostazol is a PDE3 inhibitor that increases the heart rate by about 5-8 beats per minute and has other potentially beneficial HFpEF effects such as peripheral vasodilation, lusitropic effects and dromotropic effects. By activating proteinkinase A, cilostazol may also phosphorylate titin, which may reduce myocardial stiffness.

n-of-1 study design using the standard dose cilostazol formulation of 100mg twice a day approved for peripheral vascular disease. The investigators and patients are blinded. The patients serve as their own controls with two crossovers (Week 1: cilostazol or placebo - Week 2: placebo or cilostazol - Week 3: cilostazol or placebo - Week 4: placebo or cilostazol).

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • M Health Fairview

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• >18 yrs
• LVEF ≥ 50% (on last assessment, <2 years)

• Diagnosis of HFpEF or Shortness of breath with NYHA Class ≥ 2 and one of the following:

  1. pulmonary edema on chest imaging or documented on exam or on loop diuretics
  2. NTproBNP >400 ng/ml in the last 24 months
  3. HFpEF>50% hospitalization in the last 3 years
  4. Qualitative echo: > mild diastolic dysfunction on echo report and > mild left ventricular hypertrophy and left atrial dilation or quantitative echo: left ventricular hypertrophy [men ≥115 g/m², women ≥95 g/m² or relative wall thickness >0.42 or any LV wall thickness >1.2cm and has LA dilation (>28ml/m2)

Exclusion Criteria:

• <18yo
• resting heart rate >100/min
• patients with LVEF <50%
• advanced end-stage heart failure,
• symptomatic COPD on home O2,
• uncontrolled severe HTN (SBP >160/100 mmHg)
• patients with life expectancy <6 months,
• end-stage liver cirrhosis,
• more than moderate valve disease,
• infiltrative myocardial disease
• constrictive pericarditis or myocarditis,
• patients unable to participate in follow up,
• pregnant patients or patients without reliable contraceptive agent for the duration of study participation),
• left ventricular outflow tract obstruction,
• bleeding dyscrasias, blood dyscrasias,
• Patients on oral ketoconazole, itraconazole, fluconazole, miconazole, fluvoxamine, fluoxetine, nefazodone, sertraline, erythromycin, clarithromycin or azithromycin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cilostazol; First week, Cilostazol 100mg twice a day Second week, Placebo twice a day Third week, Cilostazol 100mg twice a day Forth week, Placebo twice a day	Drug: Placebo; Placebo; Drug: Cilostazol 100Mg Tab; Cilostazol Twice a Day
Other: Placebo; First week, Placebo twice a day Second week, Cilostazol 100mg twice a day Third week, Placebo twice a day Forth week, Cilostazol 100mg twice a day	Drug: Placebo; Placebo; Drug: Cilostazol 100Mg Tab; Cilostazol Twice a Day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
KCCQ-12	The Kansas City Cardiomyopathy Questionnaire contains 12 items that measure the effect of heart failure on health and quality of life. Total scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NTproBNP	Blood marker of heart failure severity [pg/mL], average of 2 time points 1st and 3rd week	1st and 3rd week

Collaborators and Investigators

• Sponsor: University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: November 1, 2021
• First Submitted That Met QC Criteria: November 18, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Neuroprotective Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Cilostazol
• Other Study ID Numbers: CV-2020-29436

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No