Midodrine for the Treatment of Refractory Hypotension

• ClinicalTrials.gov Identifier: NCT01531959
• Recruitment Status: Completed
• First Posted: February 13, 2012
• Results First Posted: October 5, 2020
• Last Update Posted: October 28, 2020
• Sponsor: Massachusetts General Hospital
• Collaborator: Sir Charles Gairdner Hospital
• Information provided by (Responsible Party): Matthias Eikermann, MD PhD, Beth Israel Deaconess Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypotension; Critical Illness	Drug: Midodrine; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 139 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Midodrine for the Treatment of Refractory Hypotension in Patients Otherwise Ready for Discharge From the ICU
• Study Start Date: April 2012
• Actual Primary Completion Date: June 2019
• Actual Study Completion Date: June 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Midodrine	Drug: Midodrine; Patients will be randomized to blinded to 20 mg of midodrine
Placebo Comparator: Placebo	Drug: Placebo; Patients will be randomized to blinded placebo control

Outcome Measures

Primary Outcome Measures :

1. Time Until Discontinuation of IV Vasopressors [ Time Frame: 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 Outcome Measures :

1. ICU Length of Stay [ Time Frame: 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
2. Hospital Length of Stay [ Time Frame: From initiation of midodrine until hospital discharge, assessed up to 90 days ]
   Measured number of days from initiation of midodrine until discharged from hospital
3. Rates of ICU Readmission [ Time Frame: Up to 2 months after ICU discharge ]
   Number of patients initiated on midodrine that are readmitted back to ICU after being discharged to floor
4. Rates of Hypertension, Bradycardia, and Hemodynamically Significant Tacharrythmias [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Australia, Western Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia, 60009

Sponsors and Collaborators

Massachusetts General Hospital

Sir Charles Gairdner Hospital

Investigators

• Principal Investigator: Matthias Eikermann, MD, PhD; Beth Israel Deaconess Medical Center

  Study Documents (Full-Text)

Documents provided by Matthias Eikermann, MD PhD, Beth Israel Deaconess Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] March 27, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Matthias Eikermann, MD PhD, Vice Chair of Faculty Affairs of the Department of Anesthesia Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT01531959
• Other Study ID Numbers: 2011P002049; 2015-098 ( Other Identifier: Sir Charles Gairdner Hospital HREC ); 2018P000162 ( Other Identifier: Beth Israel Deaconess Medical Center )
• First Posted: February 13, 2012
• Results First Posted: October 5, 2020
• Last Update Posted: October 28, 2020
• Last Verified: October 2020

Keywords provided by Matthias Eikermann, MD PhD, Beth Israel Deaconess Medical Center:

Midodrine; Hypotension; Intensive care unit; IV vasopressors; ICU discharge

Additional relevant MeSH terms:

Hypotension; Critical Illness; Vascular Diseases; Cardiovascular Diseases; Disease Attributes; Pathologic Processes; Midodrine; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action