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

NCT ID: NCT05058612

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 870 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-22
• Study Completion Date: 2028-02-29

Brief Summary

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.

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).

Conditions

Vasoplegia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Midodrine

Midodrine 10 mg PO/NG q8h

Group Type: EXPERIMENTAL

Midodrine

Intervention Type: DRUG

10 mg PO/NG q8h

Placebo

Microcrystalline cellulose PO/NG q8h

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Microcrystalline cellulose PO/NG 18h

Interventions

Midodrine

10 mg PO/NG q8h

Intervention Type: DRUG

Placebo

Microcrystalline cellulose PO/NG 18h

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital Foundation

OTHER

Sponsor Role: collaborator

Institute of Health Economics, Canada

OTHER

Sponsor Role: collaborator

Alberta Health services

OTHER

Sponsor Role: collaborator

University of Alberta

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Oleksa Rewa, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Dawn Opgenorth, RN

Role: CONTACT

dawno@ualberta.ca

780 492-4698

Oleksa Rewa, MD

Role: CONTACT

rewa@ualberta.ca

780 492-6621

Facility Contacts

Dawn Opgenorth, RN

Role: primary

dawno@ualberta.ca

780 492-4698

Oleksa Rewa, MD

Role: backup

rewa@ualberta.ca

780 492-6621

References

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.

Reference Type: DERIVED

PMID: 35246227 (View on PubMed)

Other Identifiers

Pro00112293

Identifier Type: -

Identifier Source: org_study_id