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Midodrine Hydrochloride in Early Sepsis

Phase 1
Completed
Conditions
Sepsis
Blood Pressure
Interventions
Registration Number
NCT03129542
Lead Sponsor
Mayo Clinic
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
33
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Midodrine Hydrochloride 10 milligramsMidodrine Hydrochloride 10 milligramsThree 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.
Placebo oral capsulePlacebo capsuleFor 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.
Primary Outcome Measures
NameTimeMethod
Duration of Vasopressor Use24 hours

To study the duration of vasopressor use in the first 24 hours of sepsis

Secondary Outcome Measures
NameTimeMethod
Cumulative Vasopressor Dose24 hours after the first drug dose

To study the cumulative vasopressor dose requirements during the first 24 hours after study drug initiation

Mean arterial blood pressure (MAP)24 hours after the first drug dose

Routinely measured mean arterial blood pressure, invasive and noninvasive

ICU and hospital length of stay, central venous access use and organ failureThe first 7 days of study enrollment or until discharge

Daily Simplified Organ Failure Assessment, SOFA, scores

Cumulative Fluid Balance24 hours after sepsis onset

To study the cumulative fluid balance during the first 24 hours of sepsis

Incidence of potential side effects attributable to Midodrine48 hours after enrollment

To study the potential side effects attributable to Midodrine use in diagnosis of Sepsis.

Trial Locations

Locations (1)

Mayo Clinic in Rochester

🇺🇸

Rochester, Minnesota, United States

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