VasoplegiaPhase 4NCT05058612
Midodrine for the Early Liberation of Vasopressor Support in the ICU (LIBERATE Multi-Site)
A Phase 4 study testing Midodrine in people with Vasoplegia, run by University of Alberta at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Vasoplegia
- What is being tested?
- Midodrine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 870 participants
- Where
- 1 siteCanada
- Study dates
- 22 Mar 2021to Feb 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Ongoing vasopressor support
- Decreasing vasopressor dose(s)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
University of Alberta Hospital
Edmonton, Alberta, T5R 0T1
Dawn Opgenorth, RN, 780 492-4698, dawno@ualberta.ca
Oleksa Rewa, MD, 780 492-6621, rewa@ualberta.ca
About this study
Official title: 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.
Read the 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
- Being tested
- Midodrine, Placebo
- Keywords
- critical care medicine, intensive care, shock, midodrine
- Medical subject headings
- Vasoplegia, Shock
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidodrineDrug
10 mg PO/NG q8h
PlaceboDrug
Microcrystalline cellulose PO/NG 18h
| Study group | Role | What they receive |
|---|---|---|
| Midodrine | Experimental | Midodrine 10 mg PO/NG q8h Receives: Drug: Midodrine |
| Placebo | Placebo comparator | Microcrystalline cellulose PO/NG q8h Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 year
Secondary outcomes (10)
Mortality
28-day, hospital and 90-day mortality
Measured: 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
Measured: 1 year
Duration of vasopressor support
Duration of intravenous vasopressor support
Measured: 1 year
ICU readmission
Rate of ICU re-admissions during the index hospitalization
Measured: 1 year
Re-initiation of vasopressors
Rate of re-initiation of intravenous vasopressors during ICU stay
Measured: 1 year
Quality of life as measured by the EQ-5D-5L
The quality of life score
Measured: 1 year
ICU costs
Total cost of ICU stay
Measured: 1 year
Hospital costs
Total cost of hospital stay
Measured: 1 year
Total health care costs
Total healthcare costs
Measured: 1 year
Cost effectiveness
Incremental costs and effectiveness based on daily ICU costs
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2021
- Study start22 Mar 2021
- Primary completionMar 2027 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for VasoplegiaStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 870 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Foundation, Institute of Health Economics, Canada, Alberta Health services
- Responsible party
- Sponsor
- Investigators
- Oleksa Rewa, MD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05058612
- Sponsor's protocol ID
- Pro00112293
- Status last verified
- Jan 2026
- First submitted
- 16 Sep 2021
- Last updated
- 20 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 35246227
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Midodrine for the Early Liberation From Vasopressor Support in the ICU - The LIBERATE Multi-Site Study
- ClinicalTrials.gov ID
- NCT05058612
- Acronym / sponsor ID
- Pro00112293
- Conditions
- Vasoplegia
- Keywords
- critical care medicine, intensive care, shock, midodrine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 870 participants (estimated)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- University Hospital Foundation, Institute of Health Economics, Canada, Alberta Health services
- Study start
- 22 Mar 2021 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Feb 2028 (estimated)
- First posted
- 28 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Midodrine | Experimental | Drug: MidodrineMidodrine 10 mg PO/NG q8h |
| Placebo | Placebo comparator | Drug: PlaceboMicrocrystalline cellulose PO/NG q8h |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age > 18 years
- Ongoing vasopressor support
- Decreasing vasopressor dose(s)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Midodrine10 mg PO/NG q8h | Drug | Midodrine |
| PlaceboMicrocrystalline cellulose PO/NG 18h | Drug | Placebo |
Primary outcome
Hierarchical composite of 28-day mortality and ICU length of stay
Time frame: 1 year
The effects of midodrine on patient mortality at 28 days or total duration of patient stay in ICU
10 secondary outcomes
Mortality
Time frame: 1 year
Total and post-ICU length of stay
Time frame: 1 year
Duration of vasopressor support
Time frame: 1 year
ICU readmission
Time frame: 1 year
Re-initiation of vasopressors
Time frame: 1 year
Quality of life as measured by the EQ-5D-5L
Time frame: 1 year
ICU costs
Time frame: 1 year
Hospital costs
Time frame: 1 year
Total health care costs
Time frame: 1 year
Cost effectiveness
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2026.
- Derived from this study: PubMed 35246227Opgenorth 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Oleksa Rewa, MD principal investigator
University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Midodrine in people with Vasoplegia, run by University of Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dawn Opgenorth, RN (780 492-4698, dawno@ualberta.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hierarchical composite of 28-day mortality and ICU length of stay (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05058612, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.