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

Vasoplegia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05058612
• Other study ID #: Pro00112293
• Status: Recruiting
• Phase: Phase 4
• Start date: March 22, 2021
• Est. completion date: March 2025

Study information

• Verified date: January 2024
• Source: University of Alberta
• Contact: Dawn Opgenorth, RN
• Phone: 780 492-4698
• Email: dawno[@]ualberta.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

The LIBERATE multi-site study will continue the work of the pilot study to evaluate the role of midodrine for patients with low blood pressure in the ICU.

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 ICU length of stay.

Secondary Objectives: To compare the effect of enteral midodrine vs. placebo on: Total and post-hospital length of stay, Duration of IV vasopressor support, 90-day all-cause mortality, Rates of ICU re-admission, Rate of re-initiation of IV vasopressors.

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 is 350 patients (i.e., 175 patients per arm) with full follow-up.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Vasoplegia

Intervention

Drug:
• Midodrine
10 mg PO/NG q8h
• Placebo
Microcrystalline cellulose PO/NG 18h

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta

Sponsors (4)

Lead Sponsor	Collaborator
University of Alberta	Alberta Health services, Institute of Health Economics, Canada, University Hospital Foundation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ICU length of stay	The total duration of patient stay in ICU	1 year
Secondary	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
Secondary	Duration of vasopressor support	Duration of intravenous vasopressor support	1 year
Secondary	Mortality	All cause mortality within 90 days of study recruitment	up to 90 days
Secondary	ICU readmission	Rate of ICU re-admissions during the index hospitalization	1 year
Secondary	Re-initiation of vasopressors	Rate of re-initiation of intravenous vasopressors during ICU stay	1 year
Secondary	ICU costs	Total cost of ICU stay	1 year
Secondary	Hospital costs	Total cost of hospital stay	1 year
Secondary	Total health care costs	Total healthcare costs	1 year
Secondary	Cost effectiveness	Incremental costs and effectiveness based on daily ICU costs	1 year