Midodrine Use in Septic Shock

Study Overview
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Brief Summary
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The investigators aim to perform a randomized, double-blind, placebo-controlled trial to investigate the efficacy of midodrine in decreasing time to IV vasopressor liberation in patients with septic shock.

Detailed Description
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A growing body of literature comprising largely retrospective data seems to support the safety and efficacy of midodrine in the intensive care unit for decreasing IV vasopressor use. The investigators hypothesize that administration of midodrine in the early phase of septic shock in patients with adequate enteral access will result in a significant decrease in time to IV vasopressor liberation (increase in vasopressor-free days), secondarily resulting in decreased central venous catheter dwell times and intensive care unit length of stay.

Official Title
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Midodrine Use for Hypotension Requiring IV Vasopressor Therapy in Early Septic Shock

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: Midodrine Hydrochloride
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥18-89 years old Admitted to UVA medical ICU with diagnosis of septic shock. Patients requiring at least 5 mcg/min norepinephrine infusion (or equivalent) for blood pressure support for at least 3 hours Patients with enteral access established within 12 hours of admission (either able to swallow, or feeding tube in place) Exclusion Criteria: Pregnant females; (due to the potential adverse effects to an unborn child); patients with childbearing potential will have results of pregnancy test checked (which is routinely performed on admission); should the patient have child-bearing potential and the pregnancy status is not checked as part of routine care, such patients will be excluded from the study (i.e. pregnancy testing will not be performed for research purposes) Patients < 18 years Prisoners Patients already taking midodrine Patients with cirrhosis of the liver as defined by either biopsy, imaging findings of cirrhosis AND thrombocytopenia or patients otherwise undergoing liver transplant evaluation Patients with Increased intraocular pressure and glaucoma Patients with allergy to midodrine Non-English speaking patients, due to the narrow time-frame for study enrollment and execution of study protocol, employing interpreters is deemed to be a significant burden on the investigators with potential to hamper study enrollment. Non-english speaking patients are not deemed to be adversely affected by exclusion from study as there is no clear a priori reason why study results would not also apply to non-English speakers. Patients without enteral access within 12 hours of initiation of IV vasopressors Patients where the attending physician does not clinically intend to target a mean arterial pressure of > 65 mmHg Patients with pheochromocytoma or thyrotoxicosis Patients with active bowel ischemia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Investigational pharmacy formulated placebo. In early phase patients will be randomized to placebo, 10mg TID midodrine or 20 mg TID midodrine. (15 per group) | Other: placebo<br>* investigational pharmacy formulated placebo comparator<br>|
| Experimental: Midodrine Hydrochloride 10 mg TID<br>In early phase patients will be randomized to placebo, 10mg TID midodrine or 20 mg TID midodrine. (15 per group). After the first 45 patients are enrolled, interim safety and efficacy analysis will dictate which experimental group is continued/open to further enrollment (either 10 mg midodrine TID or 20 mg midodrine TID). | Drug: Midodrine Hydrochloride<br>* Midodrine Hydrochloride, enteral, 10 or 20 mg<br>|
| Experimental: Midodrine Hydrochloride 20 mg TID<br>In early phase patients will be randomized to placebo, 10mg TID midodrine or 20 mg TID midodrine. (15 per group). After the first 45 patients are enrolled, interim safety and efficacy analysis will dictate which experimental group is continued/open to further enrollment (either 10 mg midodrine TID or 20 mg midodrine TID). | Drug: Midodrine Hydrochloride<br>* Midodrine Hydrochloride, enteral, 10 or 20 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| days free of vasopressors (days) | days without vasopressor adjusted with mortality | 90 days from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central venous catheter free days |  | 90 days from enrollment | 
| Intensive care unit length of stay (ICU LOS; days) |  | 90 days from enrollment | 
| Hospital length of stay (Hospital LOS; days) |  | 90 days from enrollment | 
| 30-day mortality |  | 30 days from enrollment | 
| 90-day mortality |  | 90 days from enrollment | 
| In-hospital mortality | Mortality during sentinel admission | From randomization until date of death if occurred prior to discharge from sentinel hospitalization, assessed up to 52 weeks | 
| Intensive care unit mortality | Mortality during intensive care unit stay during sentinel admission | From randomization until date of death if occurred prior to discharge from the sentinel intensive care unit admission, assessed up to 52 weeks | 
| Need to re-initiate IV vasopressors 2 or more hours after discontinuation |  | From randomization until date of discharge from the sentinel intensive care unit admission, assessed up to 52 weeks |