Critical Illness, Hypotension
Conditions
Keywords
Midodrine, Hypotension, Intensive care unit, IV vasopressors, ICU discharge
Brief summary
We hypothesize that midodrine treatment of refractory hypotension in patients otherwise ready for discharge from the ICU shortens duration of receiving IV vasopressors and SICU length of stay without increasing MGH length of stay or putting the patient at risk of being readmitted to an ICU.
Detailed description
Persistent hypotension in critically ill patients remains a major barrier to discharging patients from the intensive care unit (ICU). In our hospital, in patients with adequate tissue perfusion, midodrine has been observed to treat hypotension in order to wean continuous intravenous (IV) vasopressors and therefore promote ICU discharge. There are several possible etiologies of hypotension in the ICU. The most frequently seen causes include septic shock, hypovolemia, adrenal insufficiency, and idiosyncratic reactions from medications. For patients whose reversible causes of hypotension have been addressed but still require vasopressors, midodrine may prove to be a useful adjunctive medication to successfully increase blood pressure. No previous studies have examined the use of midodrine for the treatment of hypotension in an ICU setting. Therefore, we are investigating a new indication for midodrine as the treatment of hypotension in critically ill patients.
Interventions
DRUGMidodrine
Patients will be randomized to blinded to 20 mg of midodrine
DRUGPlacebo
Patients will be randomized to blinded placebo control
Sponsors
Sir Charles Gairdner Hospital
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age * Admitted to the SICU * Requiring IV vasopressors at a rate of less than 100 mcg/min of phenylephrine, or 8 mcg/min of norepinephrine, or 60 mcg/min of metaraminol; and unable to wean for more than 24 hours while still maintaining desired blood pressure goal
Exclusion criteria
* Inadequate tissue oxygenation * Liver failure * Renal failure * Hypovolemic shock or hypotension due to adrenal insufficiency * Pregnancy * Severe organic heart disease * Urinary retention * Pheochromocytoma * Thyrotoxicosis * Midodrine as pre-admission medication * Any known allergies to midodrine * Enrollment in another clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Until Discontinuation of IV Vasopressors | From initiation of the study drug until discontinuation of IV vasopressors, assessed up to 400 hours | Measured hours from initiation of midodrine until discontinuation of IV vasopressors |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU Length of Stay | From initiation of midodrine until ICU discharge, assessed up to 45 days | Measured number of days from initiation of midodrine until discharge ready from the ICU |
| Hospital Length of Stay | From initiation of midodrine until hospital discharge, assessed up to 90 days | Measured number of days from initiation of midodrine until discharged from hospital |
| Rates of ICU Readmission | Up to 2 months after ICU discharge | Number of patients initiated on midodrine that are readmitted back to ICU after being discharged to floor |
| Rates of Hypertension, Bradycardia, and Hemodynamically Significant Tacharrythmias | From initiation of the study drug until discontinuation of the study drug, an average of 59 hours. | Measured rates of hypertension (increase in systolic blood pressure to values higher than those set by the primary team or greater than 160 mmg), bradycardia (decrease in heart rate to values lower than those set by the primary team or less than 40 BPM), hemodynamically significant tachyarrythmias (greater than 20 mmhg decrease in systolic blood pressure). |
Countries
Australia, United States
Participant flow
Pre-assignment details
139 participants provided informed consent and were enrolled. 3 participants subsequently did no loner meet eligibility criteria and were therefore not randomized, resulting in a total number of started/randomized participants of 136.
Participants by arm
| Arm | Count |
|---|---|
| Midodrine Midodrine: Patients will be randomized to blinded to 20 mg of midodrine | 66 |
| Placebo Placebo: Patients will be randomized to blinded placebo control | 66 |
| Total | 132 |
Baseline characteristics
| Characteristic | Placebo | Total | Midodrine |
|---|---|---|---|
| Age, Continuous | 66.7 years STANDARD_DEVIATION 14.7 | 68.4 years STANDARD_DEVIATION 13.7 | 70.0 years STANDARD_DEVIATION 12.6 |
| APACHE II Score | 14.8 units on a scale STANDARD_DEVIATION 5.9 | 14.7 units on a scale STANDARD_DEVIATION 5.5 | 14.7 units on a scale STANDARD_DEVIATION 5.2 |
| Body mass index | 29.8 kg/m^2 STANDARD_DEVIATION 8.8 | 28.8 kg/m^2 STANDARD_DEVIATION 8.8 | 27.9 kg/m^2 STANDARD_DEVIATION 8.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) White | 62 Participants | 126 Participants | 64 Participants |
| Sex: Female, Male Female | 34 Participants | 64 Participants | 30 Participants |
| Sex: Female, Male Male | 32 Participants | 68 Participants | 36 Participants |
| SOFA Score on admission day | 5 units on a scale | 4 units on a scale | 4 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 1 / 66 |
| other Total, other adverse events | 20 / 66 | 17 / 66 |
| serious Total, serious adverse events | 0 / 66 | 1 / 66 |
Outcome results
Primary
Time Until Discontinuation of IV Vasopressors
Measured hours from initiation of midodrine until discontinuation of IV vasopressors
Time frame: From initiation of the study drug until discontinuation of IV vasopressors, assessed up to 400 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Midodrine | Time Until Discontinuation of IV Vasopressors | 23.5 hours |
| Placebo | Time Until Discontinuation of IV Vasopressors | 22.5 hours |
Secondary
Hospital Length of Stay
Measured number of days from initiation of midodrine until discharged from hospital
Time frame: From initiation of midodrine until hospital discharge, assessed up to 90 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Midodrine | Hospital Length of Stay | 11.0 days |
| Placebo | Hospital Length of Stay | 14.0 days |
Secondary
ICU Length of Stay
Measured number of days from initiation of midodrine until discharge ready from the ICU
Time frame: From initiation of midodrine until ICU discharge, assessed up to 45 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Midodrine | ICU Length of Stay | 6.0 days |
| Placebo | ICU Length of Stay | 6.0 days |
Secondary
Rates of Hypertension, Bradycardia, and Hemodynamically Significant Tacharrythmias
Measured rates of hypertension (increase in systolic blood pressure to values higher than those set by the primary team or greater than 160 mmg), bradycardia (decrease in heart rate to values lower than those set by the primary team or less than 40 BPM), hemodynamically significant tachyarrythmias (greater than 20 mmhg decrease in systolic blood pressure).
Time frame: From initiation of the study drug until discontinuation of the study drug, an average of 59 hours.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Midodrine | Rates of Hypertension, Bradycardia, and Hemodynamically Significant Tacharrythmias | 12 Participants |
| Placebo | Rates of Hypertension, Bradycardia, and Hemodynamically Significant Tacharrythmias | 3 Participants |
Secondary
Rates of ICU Readmission
Number of patients initiated on midodrine that are readmitted back to ICU after being discharged to floor
Time frame: Up to 2 months after ICU discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Midodrine | Rates of ICU Readmission | 1 Participants |
| Placebo | Rates of ICU Readmission | 3 Participants |