Midodrine as Novel Treatment of Post-Cardiopulmonary Bypass Vasoplegic Syndrome

Vasoplegic syndrome (VS) is a common and serious complication of cardiopulmonary bypass (CPB) procedures associated with a significant increase in morbidity and mortality. VS is defined as significant hypotension, high or normal cardiac outputs, low systemic vascular resistance, low cardiac filling pressures, and vasopressor requirement despite adequate fluid resuscitation following CPB. Extensive research has been performed regarding the pathophysiologic response to CPB and risk factors associated with VS. No safe and effective preventive strategy has gained widespread use. Supportive care with intravenous (IV) vasopressors has thus been adopted as standard of care. The use of these medications, while effective in the majority of patients, generally necessitates close monitoring in an intensive care unit (ICU) setting. These patients are subject to prolonged ICU and hospital stays, as well as the potential complications of prolonged use of central venous lines (CVL) required to give these medications. Recent studies suggest midodrine, a generic oral vasopressor, may accelerate the decline in IV vasopressor requirements in select ICU patients. At our institution, the addition of midodrine to IV vasopressors for the treatment of VS has been observed to be effective in reducing IV vasopressor duration. No literature exists describing the use of midodrine in this patient population. The goal of this study is to investigate the novel use of midodrine in CPB surgery complicated by VS. Ultimately, we hope to produce literature supporting its use that may be applied on a global scale to improve patient care

Study Overview

• Status: Terminated
• Conditions: Use of Midodrine in Post-cardiopulmonary Bypass Vasoplegic Syndrome
• Intervention / Treatment: Drug: Midodrine; Drug: Methylcellulose

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

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:

• post-cardiopulmonary bypass surgery

• vasoplegic syndrome criteria

  1. MAP < 65mmHg
  2. Cardiac index>/=2.4 L/min/m^2, as determined by Swan-
  3. systemic vascular resistance index </=1400 dynes s/cm^5/m^2
  4. adequate fluid resuscitation as determined by treating critical care team

• vasopressor requirement

  1. norepinephrine 0.05-0.5 mcg/kg/min WITH/WITHOUT
  2. vasopressin any dose

Exclusion Criteria:

• allergy to midodrine
• pregnancy
• midodrine or cardiac glycoside as preadmission medication
• history of orthostatic hypotension, thyrotoxicosis, or pheochromocytoma
• severe organic heart disease (endocarditis, untreated congenital or rheumatic heart disease)
• liver failure/cirrhosis
• chronic kidney disease (GFR <30mL/hr)
• ventricular assist device implantation procedure, intra-aortic balloon pump placement, or heart transplantion
• unresolved post-operative acute kidney injury (rise in serum creatinine by >/= 0.5mg/dl from baseline
• inadequate tissue oxygenation (lactate > 2 mmol/L)
• inability to take oral medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Midodrine Arm; Patients will receive the drug Midodrine	Drug: Midodrine; Oral vasoactive that is metabolized by the liver an peripheral tissues into desglymidodrine, an active metabolite. It produces arteriolar and venous constriction with a subsequent elevation in blood pressure.
Placebo Comparator: Placebo Arm; Patients will receive placebo.	Drug: Methylcellulose; Placebo will consist of inert methylcellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time from procedure end until discontinuation of IV vasopressors	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of decline in IV vasopressor dose	12 months
Time until CVL removal	12 mothns
ICU length of stay	12 months
Hospital length of stay	12 months
Rate of major infections/complications	12 months
Rate of in-hospital and 30-day mortality	12 months

Collaborators and Investigators

• Sponsor: Medstar Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2016
• Primary Completion (Actual): August 8, 2018
• Study Completion (Actual): August 8, 2018

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 16, 2020

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Disease; Syndrome; Vasoplegia; 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: 2016-097

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No