Midodrine Hydrochloride in Early Sepsis

Study Overview
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Brief Summary
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The investigators would like to determine if early administration of oral Midodrine in participants diagnosed with sepsis will impact blood pressures and decrease the need for and/or doses of intravenous pressor agents.

Detailed Description
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Three doses of either placebo or midodrine every 8 hours will be administered in addition to usual care for sepsis. The goal will be to administer the first dose approximately within 24 hours of diagnosis. The first dose will be administered only after the patient has been admitted to the ICU. Subjects will receive treatment for a total of 16 hours starting from the first dose. The medical provider, nursing staff and patient will be blinded to randomization, only research pharmacist will be aware of randomization. Blood pressure will be recorded at least on a 4 hourly basis for 24 hours from the time of administration of the first dose, and also just prior to administration of each dose. Subsequent doses will be held if systolic blood pressure, SBP, is greater than 130 mmHg. If a subject requires initiation of intravenous vasopressor agents following study enrollment, subsequent doses will be continued. There will be no further intervention after all 3 doses have been administered; however clinical outcomes and adverse events will be monitored.

Official Title
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Oral Midodrine Hydrochloride in Early Sepsis: Randomized, Double Blind and Placebo-Controlled Feasibility Study

Conditions
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Sepsis, Blood Pressure

Intervention / Treatment
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* Drug: Midodrine Hydrochloride 10 milligrams
* Drug: Placebo capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with sepsis based on the old Sepsis criteria and meeting all of the following criteria will be considered eligible to participate in the study. Age greater than or equal to 18 years Able to safely tolerate medication either by mouth or feeding tube (i.e. absence of nausea or vomiting) Able to give consent for participation or have representative available Two or more blood pressure readings taken at least 15 minutes apart with mean arterial pressures, MAPs 70 or less Treating consultant agrees to the study plan Exclusion Criteria: Patients meeting any one of the following criteria will be excluded from participation: Women of child bearing age with the potential to become pregnant who do not have a clinically documented negative pregnancy test Current cardiogenic shock or known systolic heart failure with left ventricular ejection fraction (LVEF) < 30% Current bowel ischemia Recent Myocardial infarction within the past 3 months Current use of Monoamine Oxidase Inhibitors (MAOIs) Recent Stroke within the past 3 months Midodrine as a home medication Known allergy to Midodrine High dose vasopressor use (norepinephrine >0.25 mcg/kg/min) Lactate more than 8 mmol/L Contraindications to use: History of pheochromocytoma or thyrotoxicosis or glaucoma or ischemic bowel disease

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
Interventional Model Description: The Investigators propose a prospective, randomized, double blind, placebo-controlled pilot study on the efficacy and safety of midodrine in the treatment of sepsis.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Midodrine Hydrochloride 10 milligrams<br>Three doses of oral midodrine every 8 hours will be administered in addition to usual care for sepsis. Participants randomized to the intervention group will receive a total of 3 doses of midodrine 10 milligrams every 8 hours by mouth in the form of a tablet encapsulated in order to be identical to placebo. Participants will receive treatment for a total of 16 hours, beginning with the first dose. | Drug: Midodrine Hydrochloride 10 milligrams<br>* Three doses taken every 8 hours.<br>* Other names: Midodrine;|
| Placebo Comparator: Placebo oral capsule<br>For participants randomized to the placebo arm, an identical appearing capsule containing only Lactose Monohydrate powder will be administered every 8 hours for a total of 3 doses. | Drug: Placebo capsule<br>* Three doses taken every 8 hours.<br>* Other names: Lactose Monohydrate powder;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Vasopressor Use | To study the duration of vasopressor use in the first 24 hours of sepsis | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean arterial blood pressure (MAP) | Routinely measured mean arterial blood pressure, invasive and noninvasive | 24 hours after the first drug dose | 
| Cumulative Fluid Balance | To study the cumulative fluid balance during the first 24 hours of sepsis | 24 hours after sepsis onset | 
| ICU and hospital length of stay, central venous access use and organ failure | Daily Simplified Organ Failure Assessment, SOFA, scores | The first 7 days of study enrollment or until discharge | 
| Incidence of potential side effects attributable to Midodrine | To study the potential side effects attributable to Midodrine use in diagnosis of Sepsis. | 48 hours after enrollment | 
| Cumulative Vasopressor Dose | To study the cumulative vasopressor dose requirements during the first 24 hours after study drug initiation | 24 hours after the first drug dose |