Midodrine as Novel Treatment of Post-Cardiopulmonary Bypass Vasoplegic Syndrome

NCT04668859 | Terminated Phase 4 FDA Drug

• 1 other identifier: 2016-097
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Use of Midodrine in Post-cardiopulmonary Bypass Vasoplegic Syndrome

Outcome Measures

Primary Outcomes (1)

• Time from procedure end until discontinuation of IV vasopressors

  12 months

Secondary Outcomes (6)

• 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

Study Arms (2)

Midodrine Arm

ACTIVE COMPARATOR

Patients will receive the drug Midodrine

Drug: Midodrine

Placebo Arm

PLACEBO COMPARATOR

Patients will receive placebo.

Drug: Methylcellulose

Interventions

Midodrine DRUG

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.

Midodrine Arm

Methylcellulose DRUG

Placebo will consist of inert methylcellulose

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• post-cardiopulmonary bypass surgery
• vasoplegic syndrome criteria
• MAP \< 65mmHg
• Cardiac index\>/=2.4 L/min/m\^2, as determined by Swan-
• systemic vascular resistance index \</=1400 dynes s/cm\^5/m\^2
• adequate fluid resuscitation as determined by treating critical care team
• vasopressor requirement
• norepinephrine 0.05-0.5 mcg/kg/min WITH/WITHOUT
• vasopressin any dose

You may not qualify if:

• 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

Sponsors & Collaborators

• Medstar Health Research Institute: lead

MeSH Terms

Interventions

Midodrine; Methylcellulose

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Cellulose; Glucans; Polysaccharides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2020
• First Posted: December 16, 2020
• Study Start: July 29, 2016
• Primary Completion: August 8, 2018
• Study Completion: August 8, 2018
• Last Updated: July 1, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share