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

October 4, 2023 updated by: University of Alberta

Midodrine for the Early Liberation of Vasopressor Support in the ICU - The LIBERATE Pilot 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

The LIBERATE pilot study will evaluate the role of midodrine for patients with low blood pressure in the ICU. The investigators are planning on enrolling up to 20 study participants to evaluate this question in the General Systems ICU at the University of Alberta Hospital.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 determine if recruitment for LIBERATE is achievable and feasible To compare the effect of enteral midodrine vs placebo on duration of vasopressor support

Secondary Objective: To compare the effect of enteral midodrine vs. placebo on:

ICU length of stay 90-day all-cause mortality Rate of re-initiation of IV vasopressors Rates of ICU re-admission Adverse events Research Method/Procedures: The LIBERATE Trial is a single centre, concealed-allocation parallel-group blinded pilot RCT. 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 60 patients (i.e., 30 patients per arm) with full follow-up to ensure feasibility. Study personnel at the clinical sites will document the ICU length of stay. Daily assessment will occur for re-initiation of IV vasopressors and ICU re-admission. Patients will be followed at 90 days for mortality.

Plan for Data Analysis: Analyses of the primary and secondary outcomes will involve summary measures obtained by aggregating the endpoints using Stata software package (StataCorp, Texas, USA). Baseline comparisons will be performed using chi-squared test for equal proportions with results to be reported as numbers, percentages, and 95% confidence intervals. Continuous normally distributed variables will be compared using paired t-tests and reported as means with 95% confidence intervals, while non-normally distributed will be compared using Wilcoxon rank sum tests and reported as medians and interquartile ranges.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alberta
      • Edmonton, Alberta, Canada, T5R0T1
        • University of Alberta Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age > 18 years old
  • ICU admission
  • Ongoing vasopressor support
  • Decreasing vasopressor dose

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Midodrine
Midodrine 10mg PO/NG q8h
10mg PO/NG q8h
Other Names:
  • Midodrine Hydrochloride
Placebo Comparator: Placebo
Microcrystalline cellulose PO/NG q8h
10mg PO/NG q8h
Other Names:
  • Microcrystalline cellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recruitment Rates
Time Frame: 1 year
Recruitment metrics by patients recruitment and consent rate
1 year
Duration of vasopressor support
Time Frame: 1 year
Duration of intravenous vasopressor support
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ICU length of stay
Time Frame: 1 year
Total duration of patient stay in ICU
1 year
Mortality
Time Frame: Up to 90 days
All cause patient mortality within 90 days of study recruitment
Up to 90 days
Re-initiation of IV vasopressors
Time Frame: 1 year
Rate of re-initiation of intravenous vasopressors during ICU stay
1 year
ICU re-admissions
Time Frame: 1 year
Rates of ICU re-admissions during same hospitalization
1 year
Adverse events
Time Frame: 1 year
Rates of adverse events during ICU stay
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Oleksa G Rewa, MD MSc, University of Alberta

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 22, 2021

Primary Completion (Actual)

July 31, 2022

Study Completion (Actual)

October 30, 2022

Study Registration Dates

First Submitted

July 20, 2020

First Submitted That Met QC Criteria

July 27, 2020

First Posted (Actual)

July 28, 2020

Study Record Updates

Last Update Posted (Actual)

October 6, 2023

Last Update Submitted That Met QC Criteria

October 4, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

As this is a pilot study, all results will be used to inform the development of a larger scale, multi centre RCT.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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