Midodrine Hydrochloride in Early Sepsis

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.

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 oral intake (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

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

- History of lactose intolerance

- Current cardiogenic shock or known systolic heart failure with left ventricular
ejection fraction (LVEF) < 30%

- Current Gastrointestinal Bleeding or 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

- Fludrocortisone acetate is a current home medication

- Contraindications to use: History of pheochromocytoma or thyrotoxicosis or peripheral
vascular disease or glaucoma or ischemic bowel disease