Midodrine for the Treatment of Refractory Hypotension

Midodrine for the Treatment of Refractory Hypotension in Patients Otherwise Ready for Discharge From the ICU

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.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Hypotension
• Intervention / Treatment: Drug: Midodrine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 60009
      • Sir Charles Gairdner Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Patients will be randomized to blinded placebo control
ACTIVE_COMPARATOR: Midodrine	Drug: Midodrine; Patients will be randomized to blinded to 20 mg of midodrine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Until Discontinuation of IV Vasopressors	Measured hours from initiation of midodrine until discontinuation of IV vasopressors	From initiation of the study drug until discontinuation of IV vasopressors, assessed up to 400 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU Length of Stay	Measured number of days from initiation of midodrine until discharge ready from the ICU	From initiation of midodrine until ICU discharge, assessed up to 45 days
Hospital Length of Stay	Measured number of days from initiation of midodrine until discharged from hospital	From initiation of midodrine until hospital discharge, assessed up to 90 days
Rates of ICU Readmission	Number of patients initiated on midodrine that are readmitted back to ICU after being discharged to floor	Up to 2 months after ICU discharge
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).	From initiation of the study drug until discontinuation of the study drug, an average of 59 hours.

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Sir Charles Gairdner Hospital
• Investigators: Principal Investigator: Matthias Eikermann, MD, PhD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Anstey MH, Wibrow B, Thevathasan T, Roberts B, Chhangani K, Ng PY, Levine A, DiBiasio A, Sarge T, Eikermann M. Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: a multicenter, randomized, placebo controlled trial (the MIDAS trial). BMC Anesthesiol. 2017 Mar 21;17(1):47. doi: 10.1186/s12871-017-0339-x.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): June 1, 2019
• Study Completion (ACTUAL): June 1, 2019

Study Registration Dates

• First Submitted: February 9, 2012
• First Submitted That Met QC Criteria: February 10, 2012
• First Posted (ESTIMATE): February 13, 2012

Study Record Updates

• Last Update Posted (ACTUAL): October 28, 2020
• Last Update Submitted That Met QC Criteria: October 5, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Hypotension; Intensive care unit; Midodrine; ICU discharge; IV vasopressors
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease Attributes; Critical Illness; Hypotension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Midodrine
• Other Study ID Numbers: 2011P002049; 2015-098 (OTHER: Sir Charles Gairdner Hospital HREC); 2018P000162 (OTHER: Beth Israel Deaconess Medical Center)