Midodrine for the Treatment of Refractory Hypotension

Study Overview
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Brief Summary
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We hypothesize that midodrine treatment of refractory hypotension in patients otherwise ready for discharge from the ICU shortens duration of receiving IV vasopressors and SICU length of stay without increasing MGH length of stay or putting the patient at risk of being readmitted to an ICU.

Detailed Description
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Persistent hypotension in critically ill patients remains a major barrier to discharging patients from the intensive care unit (ICU). In our hospital, in patients with adequate tissue perfusion, midodrine has been observed to treat hypotension in order to wean continuous intravenous (IV) vasopressors and therefore promote ICU discharge. There are several possible etiologies of hypotension in the ICU. The most frequently seen causes include septic shock, hypovolemia, adrenal insufficiency, and idiosyncratic reactions from medications. For patients whose reversible causes of hypotension have been addressed but still require vasopressors, midodrine may prove to be a useful adjunctive medication to successfully increase blood pressure. No previous studies have examined the use of midodrine for the treatment of hypotension in an ICU setting. Therefore, we are investigating a new indication for midodrine as the treatment of hypotension in critically ill patients.

Official Title
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Midodrine for the Treatment of Refractory Hypotension in Patients Otherwise Ready for Discharge From the ICU

Conditions
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Hypotension, Critical Illness

Intervention / Treatment
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* Drug: Midodrine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age Admitted to the SICU Requiring IV vasopressors at a rate of less than 100 mcg/min of phenylephrine, or 8 mcg/min of norepinephrine, or 60 mcg/min of metaraminol; and unable to wean for more than 24 hours while still maintaining desired blood pressure goal Exclusion Criteria: Inadequate tissue oxygenation Liver failure Renal failure Hypovolemic shock or hypotension due to adrenal insufficiency Pregnancy Severe organic heart disease Urinary retention Pheochromocytoma Thyrotoxicosis Midodrine as pre-admission medication Any known allergies to midodrine Enrollment in another clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Midodrine<br> | Drug: Midodrine<br>* Patients will be randomized to blinded to 20 mg of midodrine<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Patients will be randomized to blinded placebo control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Until Discontinuation of IV Vasopressors | Measured hours from initiation of midodrine until discontinuation of IV vasopressors | From initiation of the study drug until discontinuation of IV vasopressors, assessed up to 400 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU Length of Stay | Measured number of days from initiation of midodrine until discharge ready from the ICU | From initiation of midodrine until ICU discharge, assessed up to 45 days | 
| Hospital Length of Stay | Measured number of days from initiation of midodrine until discharged from hospital | From initiation of midodrine until hospital discharge, assessed up to 90 days | 
| Rates of ICU Readmission | Number of patients initiated on midodrine that are readmitted back to ICU after being discharged to floor | Up to 2 months after ICU discharge | 
| Rates of Hypertension, Bradycardia, and Hemodynamically Significant Tacharrythmias | Measured rates of hypertension (increase in systolic blood pressure to values higher than those set by the primary team or greater than 160 mmg), bradycardia (decrease in heart rate to values lower than those set by the primary team or less than 40 BPM), hemodynamically significant tachyarrythmias (greater than 20 mmhg decrease in systolic blood pressure). | From initiation of the study drug until discontinuation of the study drug, an average of 59 hours. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Midodrine, Hypotension, Intensive care unit, IV vasopressors, ICU discharge