Contribution of Endothelin-1 to Exercise Intolerance in HF
Phase: EARLY_PHASE1
Conditions: Heart Failure
Sponsor: VA Office of Research and Development

Title: Contribution of Endothelin-1 to Exercise Intolerance in Heart Failure 
NCT Number: NCT02124824 
Date: December 17, 2021 
 
 

Study Objective: To compare the effect of Endothelin-1 on limb blood flow in patients with heart 
failure and healthy, age matched controls.  
 
Study Design: Single arm, unblinded. Limb blood flow will be determined in patients with heart 
failure and healthy, age-matched controls.     
 
Study Methods:  
Limb Blood Flow: An ultrasound Doppler system (Logiq 7, GE Medical Systems, Milwaukee, 
Wisconsin, USA) equipped with a linear array transducer operating at an imaging frequency of 7-
8 MHz and a Doppler frequency of 4-5 MHz will be used for determination of femoral artery 
diameter and blood velocity. 
Study drug: The ETA selective antagonist BQ-123 (0.6 mcg/dl/min) will be administered intra-
arterially (common femoral artery) rest and during knee extensor exercise (0, 5, 10, and 15 Watts).   
 
Statistical Analysis: Mixed model with repeated measures, with drug infusion at each work load 
is the dependent variable and HF (yes, no) and work load are the major predictor variables, with 
age and gender as additional explanatory variables. In a case where multivariate analysis is 
ultimately deemed appropriate and of interest, but the data do not satisfy the assumptions of 
normal distribution, we will invoke the central limit theorem and perform the bootstrap technique 
to estimate the bias and variation in the data and then correct accordingly. Because of the 
importance of ensuring a potential positive finding is not missed, no statistical adjustment will be 
made for multiple primary comparisons.