Use of Midodrine in Septic Shock Patients

Use of Midodrine in Septic Shock Patients: Phase II Randomized Clinical Meta-trial

This study is being done to determine if early administration of Midodrine can improve outcomes by maintaining a higher mean blood pressure off of intravenous medications. Researchers want to see if Midodrine can help people with sepsis need fewer vasopressors, which could mean shorter hospital stays, less time with uncomfortable tubes, and a smoother recovery overall.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Low Blood Pressure
• Intervention / Treatment: Drug: Placebo; Drug: Midodrine

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

Patients diagnosed with sepsis within 24 hours of meeting all of the following criteria will be eligible to participate in the study:

• Sepsis-3 criteria: acute hospital admission for suspected infection with new or worsening organ dysfunction measured by the increase in Sequential Organ failure Assessment (SOFA) score of 2 points or more.
• IV vasopressor use or persistent hypotension (MAP < 65 mm Hg) after initial fluid resuscitation in the ED or ICU (30 mL/kg unless deemed excessive by the treating clinician).

Exclusion criteria:

• High-dose vasopressors (norepinephrine equivalent > 0.3 µg/kg/min).
• Inadequately controlled source of infection.
• Cardiogenic or obstructive (massive pulmonary embolism) shock.
• Clinical suspicion or confirmed diagnosis of bowel obstruction, bowel ischemia, or ileus.
• Contraindication to enteral intake (ileus, vomiting, gastrointestinal bleeding, endoscopic procedures etc.).
• Recent myocardial infarction (within the past 3 months).
• Recent treatment for peripheral vascular disease (within the past 3 months).
• Current use of monoamine oxidase inhibitors.
• Recent stroke (within the past 3 months).
• Prior use of midodrine as a home medication.
• Known allergy to midodrine.
• Comfort care measures.
• Pregnancy.
• Fludrocortisone acetate as a current home medication.
• Bradycardia (heart rate < 50 beats/min).
• Untreated pheochromocytoma.
• Untreated thyrotoxicosis.
• Open-angle glaucoma.
• Treating emergency or critical care physician unwilling to enroll patient in trial.
• Inability to give consent for participation and no representative or surrogate available to consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Standard of Care Group with Placebo; Subjects will receive standard of care for sepsis and three doses of placebo every 8 hours .	Drug: Placebo; Looks and administered exactly like the study drug, but it contains no active ingredient
Experimental: Standard of Care with Midodrine Group; Subjects will receive standard of care for sepsis and three doses of midodrine every 8 hours.	Drug: Midodrine; 10 mg every 8 hours administered orally or enterally (via nasogastric tube)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time alive and without vasopressor support	Measured in hours	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total vasopressor requirements	Measured as norepinephrine equivalents (µg)	28 days
Central venous access duration	Measured in hours	28 days
Cumulative fluid balance over the first 48 hours		48 hours
Cumulative fluid balance up to 7 days of ICU stay		7 days
ICU Length of Stay	Total number of days admitted to the Intensive Care Unit (ICU)	28 days
Hospital Length of Stay	Total number of days admitted to the hospital	28 days
ICU, hospital, and organ support-free days	Number of ICU, hospital, and organ support-free days	28 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Amos Lal, MBBS, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 30, 2029
• Study Completion (Estimated): July 30, 2029

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Vasopressors
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; 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: 24-000121

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
• product manufactured in and exported from the U.S.: No