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NCT06405555

PHASE2/PHASE3

Midodrine in Heart Failure With Reduced Ejection Fraction With Hypotension

Sponsor: Ottawa Heart Institute Research Corporation

View on ClinicalTrials.gov

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.

Official title: Midodrine in Heart Failure With Reduced Ejection Fraction With Hypotension: A Pilot, Open-label, Randomized Controlled Trial

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2024-08-01

Completion Date

2026-07-01

Last Updated

2024-05-08

Healthy Volunteers

Conditions

Heart Failure With Reduced Ejection Fraction Hypotension LV Dysfunction

Interventions

DRUG

Midodrine Oral Tablet

Exposure to up to 5 days of midodrine (or until hospital discharge) in hospital at escalating doses with the following protocol: 2.5 mg po TID x 1 day, 5.0 mg po TID x 1 day, 7.5 mg po TID x 1 day, 10 mg po TID x 2 days.

Inclusion Criteria: * Adults \>= 18 years of age. * LVEF \<= 40 % within the last 3 months as determined by any one of: Transthoracic echocardiogram, transesophageal echocardiogram, cardiac magnetic resonance imaging, MUGA scan, angiogram with left ventriculogram. * AHA/ACC Stage B or C Heart Failure * Hospitalized patients in the ward setting OR in the cardiac intensive care unit (who are \>= 48 hours after their last dose of vasopressor or inotrope). * Seated upright or supine SBP \<= 100 mmHg on two or more consecutive BP measurements separated by at least 8 hours Exclusion Criteria: * Patient OR substitute decision-maker (SDM) unwilling or unable to provide informed consent * Documented allergy or intolerance to midodrine * Treatment for active infection (either documented infection or empiric treatment) with antimicrobials at the time of recruitment. * Current use OR any use within the last 48 hours of an intravenous inotrope or vasopressor medication OR the need for IV inotrope or vasoproessor use to treat hypotension * Patient within 72 hours of an acute coronary syndrome. * Heart transplant recipient. * Presence of temporary or durable mechanical circulatory support device. * Severe valvular disease expected to be intervened upon during the incident hospitalization. * Hyperkalemia \>= 5.5 mmol/L. * Baseline eGFR (as calculated by the CKD-EPI method) \<= 20 mL/min/1.73 m2 as measured within the last 3 months. * A treatable cause for hypotension, including but not limited to: hypovolemia (eg. Bleeding, overdiuresis, poor oral intake), obstructive shock, sepsis, adrenal insufficiency. * Clinical diagnosis of ongoing cardiogenic shock, or diagnosed as defined in SHOCK trial: sBP \<= 90 mmHg with evidence of end-organ hypoperfusion (cool extremities, urine output \< 30 mL/hr, HR \> 60 bpm, or elevated lactate \>=3.5 mmol/L), invasive hemodynamic measurements (if available) of CI \<= 2.2 L/min/m2 and a pulmonary capillary wedge pressure (PCWP) of \>=15 mmHg. * Pregnant patient. * Anticipated patient discharge in less than two days from enrolment (ie. less than 6 anticipated doses of midodrine, if randomized to treatment/intervention arm). * Acute brain pathology (including, but not limited to intracranial hemorrhage or hematoma) in which most-responsible clinician deems it unsafe to augment blood pressure. * Untreated thyrotoxicosis * Acute or acute on chronic liver failure * Patient unable to take oral medications * Bradycardia with resting heart rate less than 50 beats per minute. * Patients on an equivalent dose of Lasix \>= 80 mg IV BID