Critical IllnessPhase 4LIBERATENCT04489589
Midodrine for the Early Liberation of Vasopressor Support in the ICU
A Phase 4 study testing Midodrine in people with Critical Illness and Shock, 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 older
- Conditions the study is for
- Critical Illness, Shock
- What is being tested?
- Midodrine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 22 Mar 2021to 30 Oct 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years old
- ICU admission
- Ongoing vasopressor support
- Decreasing vasopressor dose
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
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 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.
- Conditions
- Critical Illness, Shock
- Being tested
- Midodrine, Placebo
- Medical subject headings
- Critical Illness, Shock
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidodrineDrug
Also called Midodrine Hydrochloride
10mg PO/NG q8h
PlaceboDrug
Also called Microcrystalline cellulose
10mg PO/NG q8h
| Study group | Role | What they receive |
|---|---|---|
| Midodrine | Experimental | Midodrine 10mg 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.
Recruitment Rates
Recruitment metrics by patients recruitment and consent rate
Measured: 1 year
Duration of vasopressor support
Duration of intravenous vasopressor support
Measured: 1 year
Secondary outcomes (5)
ICU length of stay
Total duration of patient stay in ICU
Measured: 1 year
Mortality
All cause patient mortality within 90 days of study recruitment
Measured: Up to 90 days
Re-initiation of IV vasopressors
Rate of re-initiation of intravenous vasopressors during ICU stay
Measured: 1 year
ICU re-admissions
Rates of ICU re-admissions during same hospitalization
Measured: 1 year
Adverse events
Rates of adverse events during ICU stay
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 Jul 2020
- Study start22 Mar 2021
- Primary completion31 Jul 2022
- Study completion30 Oct 2022
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 Critical IllnessStudies 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Alberta Health services, Institute of Health Economics, Canada
- Responsible party
- Sponsor
- Investigators
- Oleksa G Rewa, MD MSc, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04489589
- Sponsor's protocol ID
- Pro00096716
- Acronym
- LIBERATE
- Status last verified
- Oct 2023
- First submitted
- 20 Jul 2020
- Last updated
- 6 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: As this is a pilot study, all results will be used to inform the development of a larger scale, multi centre RCT.
Publications
Kilcommons SJ, Hammal F, Opgenorth DL, Fiest KM, Karvellas CJ, Lau VI, MacIntyre E, Senaratne J, Slemko J, Sligl W, Zampieri F, Duquette D', Guan LT, Baig N, Bagshaw SM, Rewa OG. Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): a feasibility study. Pilot Feasibility Stud. 2024 Dec 4;10(1):147. doi: 10.1186/s40814-024-01577-2.
PubMed 39633467
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Midodrine for the Early Liberation of Vasopressor Support in the ICU - The LIBERATE Pilot Study
- ClinicalTrials.gov ID
- NCT04489589
- Acronym / sponsor ID
- LIBERATE / Pro00096716
- Conditions
- Critical Illness, Shock
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- Alberta Health services, Institute of Health Economics, Canada
- Study start
- 22 Mar 2021 (actual)
- Primary completion
- 31 Jul 2022 (actual)
- Study completion
- 30 Oct 2022 (actual)
- First posted
- 28 Jul 2020 (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
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Midodrine | Experimental | Drug: MidodrineMidodrine 10mg PO/NG q8h |
| Placebo | Placebo comparator | Drug: PlaceboMicrocrystalline cellulose PO/NG q8h |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age > 18 years old
- ICU admission
- Ongoing vasopressor support
- Decreasing vasopressor dose
Key exclusion criteria (6 listed)
- 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
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 |
|---|---|---|
| MidodrineAlso: Midodrine Hydrochloride10mg PO/NG q8h | Drug | Midodrine |
| PlaceboAlso: Microcrystalline cellulose10mg PO/NG q8h | Drug | Placebo |
Primary outcome
Recruitment Rates
Time frame: 1 year
Recruitment metrics by patients recruitment and consent rate
Duration of vasopressor support
Time frame: 1 year
Duration of intravenous vasopressor support
5 secondary outcomes
ICU length of stay
Time frame: 1 year
Mortality
Time frame: Up to 90 days
Re-initiation of IV vasopressors
Time frame: 1 year
ICU re-admissions
Time frame: 1 year
Adverse events
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2023.
- Derived from this study: PubMed 39633467Kilcommons SJ, Hammal F, Opgenorth DL, Fiest KM, Karvellas CJ, Lau VI, MacIntyre E, Senaratne J, Slemko J, Sligl W, Zampieri F, Duquette D', Guan LT, Baig N, Bagshaw SM, Rewa OG. Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): a feasibility study. Pilot Feasibility Stud. 2024 Dec 4;10(1):147. doi: 10.1186/s40814-024-01577-2.
- Individual participant dataSharing planned: No. As this is a pilot study, all results will be used to inform the development of a larger scale, multi centre RCT.
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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. This study is not recruiting at the moment.
Oleksa G Rewa, MD MSc 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 Critical Illness and Shock, 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 4 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: finished, as of the sponsor's last update on 6 Oct 2023. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment Rates (time frame: 1 year). The study lists 2 primary outcomes in all. 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 NCT04489589, 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 6 Oct 2023.