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 850 subjects (425 subjects per arm). A blinded multi site pilot analysis will
be conducted after the enrolment of the first 20% of study subjects (170 subjects).