Midodrine for the Early Liberation of Vasopressor Support in the ICU (LIBERATE Multi-Site)

Midodrine for the Early Liberation From Vasopressor Support in the ICU - The LIBERATE Multi-Site Study

Vasopressors are medications that are given intravenously to increase the blood pressure of patients with illnesses that cause dangerous blood pressure drops. When a doctor prescribes a vasopressor, they ask that the dose be adjusted to achieve a specific blood pressure. This kind of medical support with intravenous (IV) vasopressors are usual treatments in intensive care unit (ICU) settings. Oral vasopressors, such as midodrine, have been historically used to maintain blood pressure in non-critically ill patients. In this study, the investigators will be using midodrine to reduce the need for IV vasopressors as blood pressure improves during the stay in the ICU.

This LIBERATE multi-site study will continue the work of the LIBERATE feasibility RCT study to evaluate the role of midodrine for patients with low blood pressure in the ICU. It is comprised of the multi centre pilot RCT followed by the definitive multi centre RCT.

Study Overview

• Status: Recruiting
• Conditions: Vasoplegia
• Intervention / Treatment: Drug: Midodrine; Drug: Placebo

Detailed Description

Purpose: Resuscitation and hemodynamic support with intravenous (IV) vasopressors is a prime indication of treatment in intensive care unit (ICU) settings. Hemodynamic support is typically provided with intravenous (IV) vasopressors. However, these have been shown to have significant negative effects including increased central venous catheter line associated infections, venous thromboembolic disease, impaired mobility and gastrointestinal injury and ischemia. Oral vasopressors, such as midodrine, have been historically used for hemodynamic support in non-critically ill patients, but their study in patients as IV pressor sparing therapy has been limited.

Hypothesis: to evaluate the expanded role of midodrine for any vasoplegic patients in the ICU.

Justification: In 2018, there were 1,613 admissions to the adult general systems ICU (GSICU) at the University of Alberta Hospital (UAH). Patients were sick, with a mean Acute Physiology and Chronic Health Evaluation II (APACHE) score of 21.3, with 36.4% requiring vasopressors on admission, accounting for 1942 patient-days (data from eCritical TRACER database). In the environment strained healthcare resources and limited ICU capacity, the ability to safely wean patients from IV vasopressors with transition to oral hemodynamic supporting agents would greatly improve how patients navigate through the healthcare system. This in turn will improve patient-centered case.

Primary Objective:

To compare the effect of enteral midodrine vs. placebo in critically ill patients with vasoplegia receiving continuous IV vasopressor therapy on a hierarchical composite of 28-day mortality and ICU length of stay.

Secondary Objectives: To compare the effect of enteral midodrine vs. placebo on: 28-day, hospital, and 90-day mortality, Duration of IV vasopressor support, Rates of ICU re-admission, Rate of re-initiation of IV vasopressors, and Quality of life at one year.

Tertiary Objectives: To determine the health economic effects of the usage of midodrine vs placebo on: ICU costs, Hospital costs, Total healthcare costs, Cost-effectiveness.

Safety Endpoints: Adverse drug reactions, Serious adverse drug reactions, Suspected unexpected serious adverse reactions.

Research Method/Procedures: The LIBERATE Trial is a multi center, concealed-allocation parallel-group blinded randomized controlled trial. Patients will be randomly assigned to midodrine (enteral, 10mg every 8h) or placebo (microcrystalline cellulose) for the duration of their IV vasopressor therapy and 24h following the discontinuation of their IV vasopressor therapy. The recruitment target for the multi centre pilot RCT is 350 subjects (i.e., 175 subjects per arm), followed by the definitive RCT with a recruitment target of 870 subjects (435 subjects per arm). A blinded multi site pilot analysis will be conducted after the enrolment of the first 20% of study subjects (170 subjects).

• Study Type: Interventional
• Enrollment (Estimated): 870
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dawn Opgenorth, RN; Phone Number: 780 492-4698; Email: dawno@ualberta.ca
• Study Contact Backup: Name: Oleksa Rewa, MD; Phone Number: 780 492-6621; Email: rewa@ualberta.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5R 0T1
      • Recruiting
      • University of Alberta Hospital
      • Contact: Dawn Opgenorth, RN; Phone Number: 780 492-4698; Email: dawno@ualberta.ca
      • Contact: Oleksa Rewa, MD; Phone Number: 780 492-6621; Email: rewa@ualberta.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age > 18 years
• Ongoing vasopressor support
• Decreasing vasopressor dose(s)

Exclusion Criteria:

• Greater than 24 hours from peak vasopressor dose
• Contraindication to enteral medications
• Previously received midodrine in last 7 days
• Expected death or anticipated withdrawal of life-sustaining therapies in next 24 hours
• Pregnancy
• Known allergy to midodrine

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
Placebo Comparator: Placebo; Microcrystalline cellulose PO/NG q8h	Drug: Placebo; Microcrystalline cellulose PO/NG 18h
Experimental: Midodrine; Midodrine 10 mg PO/NG q8h	Drug: Midodrine; 10 mg PO/NG q8h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hierarchical composite of 28-day mortality and ICU length of stay	The effects of midodrine on patient mortality at 28 days or total duration of patient stay in ICU	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of vasopressor support	Duration of intravenous vasopressor support	1 year
Total and post-ICU length of stay	The total duration of patient stay in hospital and the duration of hospital stay after ICU discharge	1 year
ICU readmission	Rate of ICU re-admissions during the index hospitalization	1 year
Re-initiation of vasopressors	Rate of re-initiation of intravenous vasopressors during ICU stay	1 year
ICU costs	Total cost of ICU stay	1 year
Hospital costs	Total cost of hospital stay	1 year
Total health care costs	Total healthcare costs	1 year
Cost effectiveness	Incremental costs and effectiveness based on daily ICU costs	1 year
Mortality	28-day, hospital and 90-day mortality	1 year
Quality of life as measured by the EQ-5D-5L	The quality of life score	1 year

Collaborators and Investigators

• Sponsor: University of Alberta
• Collaborators: Alberta Health services; Institute of Health Economics, Canada; University Hospital Foundation
• Investigators: Principal Investigator: Oleksa Rewa, MD, University of Alberta

Publications and helpful links

General Publications

• Opgenorth D, Baig N, Fiest K, Karvellas C, Kutsogiannis J, Lau V, Macintyre E, Senaratne J, Slemko J, Sligl W, Wang X, Bagshaw SM, Rewa OG. LIBERATE: a study protocol for midodrine for the early liberation from vasopressor support in the intensive care unit (LIBERATE): protocol for a randomized controlled trial. Trials. 2022 Mar 4;23(1):194. doi: 10.1186/s13063-022-06115-0.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: September 16, 2021
• First Submitted That Met QC Criteria: September 16, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: shock; intensive care; midodrine; critical care medicine
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Vasoplegia; Organic Chemicals; Amines; Alcohols; Amino Alcohols; Ethanolamines; Midodrine
• Other Study ID Numbers: Pro00112293

Drug and device information, study documents

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