Midodrine Use in Septic Shock

Midodrine Use for Hypotension Requiring IV Vasopressor Therapy in Early Septic Shock

The investigators aim to perform a randomized, double-blind, placebo-controlled trial to investigate the efficacy of midodrine in decreasing time to IV vasopressor liberation in patients with septic shock.

Study Overview

• Status: Terminated
• Conditions: Septic Shock
• Intervention / Treatment: Other: placebo; Drug: Midodrine Hydrochloride

Detailed Description

A growing body of literature comprising largely retrospective data seems to support the safety and efficacy of midodrine in the intensive care unit for decreasing IV vasopressor use. The investigators hypothesize that administration of midodrine in the early phase of septic shock in patients with adequate enteral access will result in a significant decrease in time to IV vasopressor liberation (increase in vasopressor-free days), secondarily resulting in decreased central venous catheter dwell times and intensive care unit length of stay.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients aged ≥18-89 years old
• Admitted to UVA medical ICU with diagnosis of septic shock.
• Patients requiring at least 5 mcg/min norepinephrine infusion (or equivalent) for blood pressure support for at least 3 hours
• Patients with enteral access established within 12 hours of admission (either able to swallow, or feeding tube in place)

Exclusion Criteria:

• Pregnant females; (due to the potential adverse effects to an unborn child); patients with childbearing potential will have results of pregnancy test checked (which is routinely performed on admission); should the patient have child-bearing potential and the pregnancy status is not checked as part of routine care, such patients will be excluded from the study (i.e. pregnancy testing will not be performed for research purposes)
• Patients < 18 years
• Prisoners
• Patients already taking midodrine
• Patients with cirrhosis of the liver as defined by either biopsy, imaging findings of cirrhosis AND thrombocytopenia or patients otherwise undergoing liver transplant evaluation
• Patients with Increased intraocular pressure and glaucoma
• Patients with allergy to midodrine
• Non-English speaking patients, due to the narrow time-frame for study enrollment and execution of study protocol, employing interpreters is deemed to be a significant burden on the investigators with potential to hamper study enrollment. Non-english speaking patients are not deemed to be adversely affected by exclusion from study as there is no clear a priori reason why study results would not also apply to non-English speakers.
• Patients without enteral access within 12 hours of initiation of IV vasopressors
• Patients where the attending physician does not clinically intend to target a mean arterial pressure of > 65 mmHg
• Patients with pheochromocytoma or thyrotoxicosis
• Patients with active bowel ischemia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Investigational pharmacy formulated placebo. In early phase patients will be randomized to placebo, 10mg TID midodrine or 20 mg TID midodrine. (15 per group)	Other: placebo; investigational pharmacy formulated placebo comparator
Experimental: Midodrine Hydrochloride 10 mg TID; In early phase patients will be randomized to placebo, 10mg TID midodrine or 20 mg TID midodrine. (15 per group). After the first 45 patients are enrolled, interim safety and efficacy analysis will dictate which experimental group is continued/open to further enrollment (either 10 mg midodrine TID or 20 mg midodrine TID).	Drug: Midodrine Hydrochloride; Midodrine Hydrochloride, enteral, 10 or 20 mg
Experimental: Midodrine Hydrochloride 20 mg TID; In early phase patients will be randomized to placebo, 10mg TID midodrine or 20 mg TID midodrine. (15 per group). After the first 45 patients are enrolled, interim safety and efficacy analysis will dictate which experimental group is continued/open to further enrollment (either 10 mg midodrine TID or 20 mg midodrine TID).	Drug: Midodrine Hydrochloride; Midodrine Hydrochloride, enteral, 10 or 20 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days Free of Vasopressors (Days)	days without vasopressor adjusted with mortality	90 days from enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central Venous Catheter Free Days		90 days from enrollment
Intensive Care Unit Length of Stay (ICU LOS; Days)		90 days from enrollment
Hospital Length of Stay (Hospital LOS; Days)		90 days from enrollment
30-day Mortality		30 days from enrollment
90-day Mortality		90 days from enrollment
In-hospital Mortality	Mortality during sentinel admission	From randomization until date of death if occurred prior to discharge from sentinel hospitalization, assessed up to 52 weeks
Intensive Care Unit Mortality	Mortality during intensive care unit stay during sentinel admission	From randomization until date of death if occurred prior to discharge from the sentinel intensive care unit admission, assessed up to 52 weeks
Need to Re-initiate IV Vasopressors 2 or More Hours After Discontinuation		From randomization until date of discharge from the sentinel intensive care unit admission, assessed up to 52 weeks

Collaborators and Investigators

• Sponsor: University of Virginia
• Investigators: Principal Investigator: Alexandra Kadl, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2018
• Primary Completion (Actual): February 11, 2022
• Study Completion (Actual): February 11, 2022

Study Registration Dates

• First Submitted: September 26, 2018
• First Submitted That Met QC Criteria: October 11, 2018
• First Posted (Actual): October 15, 2018

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Shock, Septic; Organic Chemicals; Amines; Alcohols; Amino Alcohols; Ethanolamines; Midodrine
• Other Study ID Numbers: 20889

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