MID-STEP (MIDodrine for Sepsis Treatment and Early vasoPressor Weaning) 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: Recruiting
• Conditions: Sepsis; Low Blood Pressure
• Intervention / Treatment: Other: Standard of Care; Drug: Midodrine

• Study Type: Interventional
• Enrollment (Estimated): 308
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amy Schuchard; Phone Number: 507-255-0148; Email: Schuchard.Amy@mayo.edu
• Study Contact Backup: Name: Aysun Tekin, MD, MS; Phone Number: 347-421-9114; Email: Tekin.Aysun@mayo.edu

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic Arizona
      • Contact: Suraj Phull; Phone Number: 480-574-5993; Email: Phull.Suraj@mayo.edu
      • Sub-Investigator: Rodrigo Cartin-Ceba, MD
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Florida
      • Contact: Gabrielle Pariseau; Phone Number: 904-956-4079; Email: Pariseau.Gabrielle@mayo.edu
      • Sub-Investigator: Devang K. Sanghavi, MBBS, MD
  • Minnesota
    • Mankato, Minnesota, United States, 56001
      • Recruiting
      • Mayo Clinic Health System - Mankato
      • Contact: Amy Schuchard; Phone Number: 507-255-0148; Email: Schuchard.Amy@mayo.edu
      • Principal Investigator: Amos Lal, MBBS
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Minnesota
      • Principal Investigator: Ognjen Gajic, MD
      • Contact: Amy Schuchard; Phone Number: 507-255-0148; Email: Schuchard.Amy@mayo.edu
      • Principal Investigator: Amos Lal, MBBS
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54703
      • Recruiting
      • Mayo Clinic Health System - Eau Claire
      • Contact: Amy Schuchard; Phone Number: 507-255-0148; Email: Schuchard.Amy@mayo.edu
      • Sub-Investigator: Juan Pablo Domecq Garces, MD

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 (STEMI or NSTEMI Type 1 within the past 3 months)
• Recent treatment for peripheral vascular disease (within the past 3 months) or acute limb ischemia
• 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
• Bradycardia (heart rate < 50 beats/min)
• Untreated pheochromocytoma
• Untreated thyrotoxicosis
• Acute Angle-Closure Glaucoma
• Cirrhosis or liver failure with Child-Pugh Score > 12
• Venous blood lactate > 4
• 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
Active Comparator: Standard of Care Group	Other: Standard of Care; Subjects will receive standard of care for sepsis treatment.
Experimental: Standard of Care with Midodrine Group	Drug: Midodrine; Subjects will receive standard of care for sepsis and 10 mg of Midodrine 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
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Ognjen Gajic, MD, Mayo Clinic; Principal Investigator: Amos Lal, MBBS, Mayo Clinic

Publications and helpful links

General Publications

• Tekin A, Halpern G, Gowda D, Bansal V, Schuchard A, Joguncic A, Schulte P, Odeyemi YE, Ahmad S, Madsen B, Rizwan Z, Barreto EF, Reddy S, Bhavsar V, Sanghavi D, Domecq Garces JP, Khan SA, Shiari A, Cartin-Ceba R, Gajic O, Lal A. Midodrine for Sepsis Treatment and Early Vasopressor Weaning (MID-STEP): protocol for a pragmatic randomised clinical trial. BMJ Open. 2026 Apr 22;16(4):e117846. doi: 10.1136/bmjopen-2026-117846.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2024
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): June 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): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Vasopressors
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis; Hypotension; Health Services Administration; Health Care Quality, Access, and Evaluation; Organic Chemicals; Quality of Health Care; Quality Indicators, Health Care; Amines; Alcohols; Amino Alcohols; Ethanolamines; Midodrine; Standard of Care
• Other Study ID Numbers: 24-000121; 1R61HL177037 (U.S. NIH Grant/Contract)

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