Midodrine in Heart Failure With Reduced Ejection Fraction With Hypotension

Registry record from ClinicalTrials.gov (NCT06405555). This is a study registration, not published results. Lead sponsor: Ottawa Heart Institute Research Corporation. Recruitment status: RECRUITING. Phase: PHASE2, PHASE3. Study type: INTERVENTIONAL. Enrollment: 56 participants (ESTIMATED). Conditions: Heart Failure With Reduced Ejection Fraction, Hypotension, LV Dysfunction. Interventions: DRUG: Midodrine Oral Tablet. Primary outcome measures: Enrollment rate , From the date of enrolment of the first study participant, to the date of enrolment of up to 56 patients, assessed up to a maximum of 80 weeks (20 months); Percent enrollment , From the date of enrolment of the first study participant, to the date of enrolment of up to 56 patients, assessed up to a maximum of 80 weeks (20 months); Randomization proportion , From the date of enrolment of the first study participant, to the date of enrolment of up to 56 patients, assessed up to a maximum of 80 weeks (20 months); Percentage of protocol completion , From the date of enrolment of the first study participant, to the date of enrolment of up to 56 patients, assessed up to a maximum of 80 weeks (20 months); Percentage lost to follow-up , From the date of enrolment of the first study participant, to the date of enrolment of up to 56 patients, assessed up to a maximum of 80 weeks (20 months). Brief summary: The evidence-based pharmacologic treatments available for patients with heart failure with reduced ejection fraction (HFrEF) has been established over the last few decades of cardiovascular research. These treatments, termed Foundational Guideline-Directed-Medical Therapies (GDMT), prolong patient life, improve patient-reported symptoms, and reduce hospitalizations for heart failure. A direct effect of most medication classes encompassed within GDMT is the reduction in blood pressure due to their mechanisms of action. In addition, as patients with HFrEF become more advanced in their disease, a significant proportion develop hypotension related to pump failure and autonomic dysfunction, amongst other possible mechanisms. As a result, a significant proportion of HFrEF patients are not optimized on GDMT with hypotension as their limiting barrier that would otherwise have served to improve their heart function, heart failure symptoms, and mortality. Currently, there does not exist any evidence-based strategies to address the problem of hypotension in HFrEF patients who are not optimized on GDMT. Midodrine is an alpha-adrenergic agonist (α1-AR) that exerts its effects on peripheral venous and arteriolar vasculature to increase blood pressure. This medication has been used off-label by some clinicians in the hypotensive HFrEF population to increase blood pressure and has been reported to have beneficial effects in improving GDMT utilization as well as increasing left ventricular ejection fraction (LVEF) in published case reports/case series. There does not exist any randomized prospective data on the use of midodrine in the hypotensive HFrEF population. The investigators' objective is to complete the first open-label, randomized control trial of midodrine in the hypotensive HFrEF population to demonstrate feasibility in performing a trial in this patient population and to show efficacy in increasing blood pressure without associated harm. The results of this trial will be used as the foundation and rationale for future studies assessing the impact of midodrine use on GDMT utilization as well as hard cardiovascular outcomes in the hypotensive HFrEF population, including hospitalizations for heart failure and mortality.