A Phase 2/3 interventional study of Midodrine Oral Tablet in Heart Failure With Reduced Ejection Fraction, Hypotension and LV Dysfunction, sponsored by Ottawa Heart Institute Research Corporation. Recruiting at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-08.
Sponsored by Ottawa Heart Institute Research Corporation · Phase 2/3, Interventional, and Treatment
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.
This will be a pilot, open-label, randomized controlled trial with the intervention/treatment being midodrine in hospitalized patients with HFrEF. The comparator/control arm will be patients following standard of care, which is to undergo no further pharmacologic intervention directed at hypotension unless clinically indicated. Patients who meet inclusion criteria will be randomized (1:1) to either midodrine group or control group, which will occur at the time of recruitment. In the treatment group, patients will receive midodrine for a total planned duration of up to 5 days, or until hospital discharge, whichever comes first. The midodrine will initially be started at 2.5 mg po TID for 1 day, followed by 5.0 mg po TID x 1 day, 7.5 mg po TID x 1 day, and 10 mg po TID x 2 days. Side effects reported by patients and any adverse drug events will be documented. At the end of the inpatient study period, continuation of midodrine off-label will be at the treating clinician's discretion in the treatment arm.
For patients discharged home less than 1 week from the exposure period, patients will be followed for 2 weeks with the Telehome monitoring program (THM), which is a virtual outpatient service intended to closely follow heart failure patients, to monitor blood pressure, heart rate, weight and adverse events or side effects. For patients discharged home between 1 to 2 weeks from the exposure period, they will be followed for 1 week with THM. For patients discharged after 2 or more weeks from the exposure period, no THM follow-up will occur. Frequency of THM follow-up, as well as inpatient monitoring parameters is as outlined in the "Data Capture" section.
Key clinical measurements will be obtained in both treatment and control arms including blood pressure measurements (every 6 hours while awake, with each measurement in the treatment arm consisting of BP measured 1 hour after the administration of midodrine dose and in the supine position. For patients in the control arm, a similar frequency of blood pressures will be obtained at pre-specified times), NT-proBNP at the time of recruitment (Day 0, prior to administration of midodrine in treatment arm) and after 5 days (ie. Sample obtained at time of last dose at Day 4 or at Day 5) or hospital discharge (whichever comes first). Safety outcomes will be monitored for and assessed. The study will be open-label and neither the patient nor the treating physicians will be blinded in this study.
885 studies on the registry are indexed under Hypotension; 195 are open to participants now.
This study's planned enrollment of 56 is below the median of 87 across 590 interventional studies indexed under Hypotension.
Browse Hypotension studies →Ottawa Heart Institute Research Corporation is the lead sponsor of 182 studies on the registry; 42 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Midodrine Oral Tablet
Patients randomized to the control arm will receive usual standard of care treatments without addition of midodrine.
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.
Also known as: Midodrine hydrochloride
Enrollment rate
Number of participants enrolled per week
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
Number of participants enrolled divided by number screened eligible
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
Number of participants randomized divided by number of participants enrolled
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
Number of participants completing the study protocol divided by the number of participants randomized.
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
Number of participants lost to follow-up divided by number of participants randomized.
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)
SBP at baseline compared to Day 4 or hospital discharge if earlier
Measurement of systolic blood pressure averaged over at least two measurements per day at study enrolment compared to average systolic blood pressure averaged over at least three measures on Day 4, or hospital discharge if earlier. The measurement is numerical difference in systolic blood pressure averages (mmHg). Blood pressure measurements are both supine lying measurements.
Time frame: Measures from time of enrolment (Day -1 or 0) and Day 4, or hospital discharge if earlier
Proportion of patients achieving sBP > 105 mmHg on Day 4 or hospital discharge if earlier
Measurement of systolic blood pressure averaged over at least three measures on Day 4, or hospital discharge if earlier. The measurement is numerical percentage. Blood pressure measurements are both supine lying measurements.
Time frame: Measurement from Day 4 of study protocol, or hospital discharge if earlier
DBP at baseline compared to Day 4 or hospital discharge if earlier
Measurement of diastolic blood pressure averaged over at least two measurements per day at study enrolment compared to average diastolic blood pressure averaged over at least three measures on Day 4, or hospital discharge if earlier. The measurement is numerical difference in diastolic blood pressure averages (mmHg). Blood pressure measurements are both supine lying measurements.
Time frame: Measures from time of enrolment (Day -1 or 0) and Day 4, or hospital discharge if earlier
NT-proBNP at baseline compared to Day 4 or hospital discharge if earlier.
Measurement of NT-proBNP blood test at baseline at time of study enrolment minus the measurement of NT-proBNP at Day 4 of the study protocol, or hospital discharge if earlier.
Time frame: Measures from time of enrolment (Day -1, or earlier if available) and Day 4, or hospital discharge if earlier
Time from randomization to hospital discharge (days).
Date of hospital discharge subtracted by date of study randomization, expressed in days.
Time frame: From the date of participant randomization to the date of discharge from hospital (to home, rehabilitation or transitional institution, long-term care/nursing home), up to 4 weeks.
Hypotension events with SBP<80 mmHg within 48 hours of discontinuation of midodrine not attributable to other reversible causes
Blood pressure event is recorded with systolic blood pressure \< 80 mmHg during the study protocol in patients on midodrine where the team involved within the participants clinical circle of care do not have other attributable reversible causes.
Time frame: From time of study Day 4 (or last day of midodrine exposure) up to 48 hours after last exposure.
Number of GDMT drugs at any dosage
Average number of Guideline Directed Medical Therapy medications for HFrEF (of the following medication classes: (1) ACEi/ARB/ARNI, (2)Beta-blocker, (3) Mineralocorticoid Receptor Antagonist, (4) SGLT2i) in the midodrine group and control groups.
Time frame: Days 0, 4 (or hospital discharge if earlier), and at up to 4 weeks (Day 27) at the end of the protocol..
Number of GDMT drugs at >= 50% of goal trial dosages as outlined in clinical practice guidelines
Average number of Guideline Directed Medical Therapy medications for HFrEF (of the following medication classes: (1) ACEi/ARB/ARNI, (2)Beta-blocker, (3) Mineralocorticoid Receptor Antagonist, (4) SGLT2i) at \>=50% of goal trial dosages as outlined in the CCS/CHFS 2021 HFrEF guidelines in the midodrine group and control groups.
Time frame: Days 0, 4 (or hospital discharge if earlier), and at up to 4 weeks (Day 27) at the end of the protocol..
Heart Failure Collaboratory(HFC) score
Heart Failure Collaboratory score calculated in the midodrine and control groups. Minimum 0, Maximum 8, with higher scores reflecting better outcomes.
Time frame: Days 0, 4 (or hospital discharge if earlier), and at up to 4 weeks (Day 27) at the end of the protocol..
Number of hospital re-admissions within 4 weeks of inpatient exposure period
Number of hospital admissions in the timeframe specified in both midodrine and control groups.
Time frame: From time of study Day 0 to 28 days (inclusive) after inpatient exposure period (up to five days).
Number of hospitalizations for heart failure within 4 weeks of inpatient exposure period
Number of hospital admissions for heart failure in the timeframe specified in both midodrine and control groups.
Time frame: From time of study Day 0 to 28 days (inclusive) after inpatient exposure period (up to five days).
Number of deaths within 4 weeks of protocol completion
Number of deaths in the timeframe specified in both midodrine and control groups.
Time frame: From time of study Day 0 to 28 days (inclusive) after inpatient exposure period (up to five days).
Heart rate
Heart rate average measurement at baseline at time of enrolment and Day 4 (or hospital discharge if earlier) in both midodrine and control groups.
Time frame: Physiologic parameters at baseline and Day 4 (if available) or hospital discharge if earlier.
Sodium laboratory value
Blood test. Units in mmol/L.
Time frame: Biochemical parameters at baseline and Day 4 (if available) or hospital discharge if earlier.
Potassium laboratory value
Blood test. Units in mmol/L.
Time frame: Biochemical parameters at baseline and Day 4 (if available) or hospital discharge if earlier.
Chloride laboratory value
Blood test. Units in mmol/L.
Time frame: Biochemical parameters at baseline and Day 4 (if available) or hospital discharge if earlier.
Bicarbonate (HCO3) laboratory value
Blood test. Units in mmol/L.
Time frame: Biochemical parameters at baseline and Day 4 (if available) or hospital discharge if earlier.
Urea laboratory value
Blood test. Units in mmol/L.
Time frame: Biochemical parameters at baseline and Day 4 (if available) or hospital discharge if earlier.
Creatinine laboratory value
Blood test. Units in micromol/L (umol/L)
Time frame: Biochemical parameters at baseline and Day 4 (if available) or hospital discharge if earlier.
Alanine Transaminase (ALT) laboratory value
Blood test. Units in U/L (Units/L)
Time frame: Biochemical parameters at baseline and Day 4 (if available) or hospital discharge if earlier.
Aspartate Transaminase (AST) laboratory value
Blood test. Units in U/L (Units/L)
Time frame: Biochemical parameters at baseline and Day 4 (if available) or hospital discharge if earlier.
Alkaline Phosphatase (ALP) laboratory value
Blood test. Units in U/L (Units/L)
Time frame: Biochemical parameters at baseline and Day 4 (if available) or hospital discharge if earlier.
Total Bilirubin (TBili) laboratory value
Blood test. Units in micromol/L (umol/L).
Time frame: Biochemical parameters at baseline and Day 4 (if available) or hospital discharge if earlier.
Number of serious adverse events after initiation of midodrine.
Defined as any untoward medical occurrence that: * Results in death * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity (i.e. a substantial disruption in an individual's ability to conduct normal life functions) * Is a congenital anomaly or birth defect * Other medically important condition that, based on medical judgment, may jeopardize the patient, and may require medical or surgical intervention to prevent one of the outcomes listed above
Time frame: At Day 0 (or hospital discharge if earlier) up to 48 hours after last dose of midodrine
Midodrine intolerance
Intolerance defined as the percentage of patients that needed to stop taking midodrine due to any AE or SAE, or other reasons as indicated by the patient.
Time frame: At Day 0 to Day 4 (or hospital discharge if earlier).
Adverse Drug Reactions (ADR) reported after initiating midodrine
* Supine hypertension (SBP\>160 mmHg) * New bradycardia (if HR \< 50 bpm) * Genitourinary symptoms (Increased urinary frequency, retention, incomplete emptying, dysuria) * Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea) * Pilomotor reaction * Paresthesia * Pruritis * Chills * Worsening pain (including headache) * Rash * Other
Time frame: At Day 0 (or hospital discharge if earlier) up to 48 hours after last dose of midodrine
Plan to share: Yes — Deidentified IPD will be made available upon request to qualified researchers requesting the data for scientific analysis.
No publications or documents are linked to this record.
Started Aug 2026 (actual). Primary completion is estimated for Jun 2028, 21 months after the start.
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Studies of the drug tested here: Midodrine
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