Recruiting
Phase 2
Phase 3

Midodrine

Sponsor:

Ottawa Heart Institute Research Corporation

Code:

NCT06405555

Conditions

Heart Failure With Reduced Ejection Fraction

Hypotension

LV Dysfunction

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Midodrine Oral Tablet

Study Details

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.

Conditions

Heart Failure With Reduced Ejection Fraction

Hypotension

LV Dysfunction

Study ID

NCT06405555

Start date

Aug 7, 2026

Status verified date

Aug, 2026

Completion date

Jun 1, 2028

Anticipated

Primary completion date

Jun 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

56 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Midodrine treatment

Patients randomized to receive midodrine for up to 5 days in hospital at escalating doses starting at 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. Patients may be discharged from hospital prior to completion of the full 5 day protocol. All patients in the midodrine treatment arm will receive otherwise usual standard of care treatments.

no intervention: Control

Patients randomized to the control arm will receive usual standard of care treatments without addition of midodrine.

Interventions

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.

Primary outcome measure

  • Enrollment rate [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) ]

Central Contacts and Locations

Central contacts

Ian Paterson, MD

6136967000dpaterson@ottawaheart.ca

Shihab Sarwar, MD

ssarwar@ottawaheart.ca

Locations

University of Ottawa Heart Institute

Recruiting

Ottawa, Ontario, Canada, K1Y 4W7

Contacts

Poppy MacPhee, RN

613-696-7000pmacphee@ottawaheart.ca

Principal Investigator:

Ian Paterson, MD

More Information

Sponsor

Ottawa Heart Institute Research Corporation

Last update posted

Sep 8, 2026

Last verified

Aug, 2026

Keywords

  • Heart Failure
  • GDMT
  • Midodrine

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Ottawa Heart Institute Research Corporation on 2026-09-08.