Midodrine Hydrochloride in Early Sepsis

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

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.

Study Overview

• Status: Completed
• Conditions: Sepsis; Blood Pressure
• Intervention / Treatment: Drug: Midodrine Hydrochloride 10 milligrams; Drug: Placebo capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Midodrine Hydrochloride 10 milligrams; 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; Three doses taken every 8 hours.; Other Names: Midodrine
Placebo Comparator: Placebo oral capsule; 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; Three doses taken every 8 hours.; Other Names: Lactose Monohydrate powder

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Cleveland Clinic Abu Dhabi
• Investigators: Principal Investigator: Ognjen Gajic, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2017
• Primary Completion (Actual): April 28, 2020
• Study Completion (Actual): May 15, 2020

Study Registration Dates

• First Submitted: April 6, 2017
• First Submitted That Met QC Criteria: April 23, 2017
• First Posted (Actual): April 26, 2017

Study Record Updates

• Last Update Posted (Actual): February 5, 2021
• Last Update Submitted That Met QC Criteria: February 4, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Midodrine
• Other Study ID Numbers: 16-002444

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No