Midodrine Use in Septic Shock

Phase 3

Terminated

• Conditions: Septic Shock
• Interventions: Other: placebo; Drug: Midodrine Hydrochloride

• Registration Number: NCT03706053
• Lead Sponsor: University of Virginia

Brief Summary

The investigators aim to perform a randomized, double-blind, placebo-controlled trial to investigate the efficacy of midodrine in decreasing time to IV vasopressor liberation in patients with septic shock.

Detailed Description

A growing body of literature comprising largely retrospective data seems to support the safety and efficacy of midodrine in the intensive care unit for decreasing IV vasopressor use. The investigators hypothesize that administration of midodrine in the early phase of septic shock in patients with adequate enteral access will result in a significant decrease in time to IV vasopressor liberation (increase in vasopressor-free days), secondarily resulting in decreased central venous catheter dwell times and intensive care unit length of stay.

Study Timeline

• Study First Submitted: 2018-09-26
• Study First Submitted QC: 2018-10-11
• Study First Posted: 2018-10-15
• Study Start: 2018-11-05
• Status Verified: 2022-02
• Primary Completion: 2022-02-11
• Study Completion: 2022-02-11
• Last Update Submitted: 2022-02-17
• Last Update Posted: 2022-03-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Patients aged ≥18-89 years old
• Admitted to UVA medical ICU with diagnosis of septic shock.
• Patients requiring at least 5 mcg/min norepinephrine infusion (or equivalent) for blood pressure support for at least 3 hours
• Patients with enteral access established within 12 hours of admission (either able to swallow, or feeding tube in place)

Exclusion Criteria

• Pregnant females; (due to the potential adverse effects to an unborn child); patients with childbearing potential will have results of pregnancy test checked (which is routinely performed on admission); should the patient have child-bearing potential and the pregnancy status is not checked as part of routine care, such patients will be excluded from the study (i.e. pregnancy testing will not be performed for research purposes)
• Patients < 18 years
• Prisoners
• Patients already taking midodrine
• Patients with cirrhosis of the liver as defined by either biopsy, imaging findings of cirrhosis AND thrombocytopenia or patients otherwise undergoing liver transplant evaluation
• Patients with Increased intraocular pressure and glaucoma
• Patients with allergy to midodrine
• Non-English speaking patients, due to the narrow time-frame for study enrollment and execution of study protocol, employing interpreters is deemed to be a significant burden on the investigators with potential to hamper study enrollment. Non-english speaking patients are not deemed to be adversely affected by exclusion from study as there is no clear a priori reason why study results would not also apply to non-English speakers.
• Patients without enteral access within 12 hours of initiation of IV vasopressors
• Patients where the attending physician does not clinically intend to target a mean arterial pressure of > 65 mmHg
• Patients with pheochromocytoma or thyrotoxicosis
• Patients with active bowel ischemia

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Investigational pharmacy formulated placebo. In early phase patients will be randomized to placebo, 10mg TID midodrine or 20 mg TID midodrine. (15 per group)
Midodrine Hydrochloride 10 mg TID	Midodrine Hydrochloride	In early phase patients will be randomized to placebo, 10mg TID midodrine or 20 mg TID midodrine. (15 per group). After the first 45 patients are enrolled, interim safety and efficacy analysis will dictate which experimental group is continued/open to further enrollment (either 10 mg midodrine TID or 20 mg midodrine TID).
Midodrine Hydrochloride 20 mg TID	Midodrine Hydrochloride	In early phase patients will be randomized to placebo, 10mg TID midodrine or 20 mg TID midodrine. (15 per group). After the first 45 patients are enrolled, interim safety and efficacy analysis will dictate which experimental group is continued/open to further enrollment (either 10 mg midodrine TID or 20 mg midodrine TID).

Primary Outcome Measures

Name	Time	Method
days free of vasopressors (days)	90 days from enrollment	days without vasopressor adjusted with mortality

Secondary Outcome Measures

Name	Time	Method
Intensive care unit length of stay (ICU LOS; days)	90 days from enrollment
30-day mortality	30 days from enrollment
90-day mortality	90 days from enrollment
In-hospital mortality	From randomization until date of death if occurred prior to discharge from sentinel hospitalization, assessed up to 52 weeks	Mortality during sentinel admission
Need to re-initiate IV vasopressors 2 or more hours after discontinuation	From randomization until date of discharge from the sentinel intensive care unit admission, assessed up to 52 weeks
Central venous catheter free days	90 days from enrollment
Hospital length of stay (Hospital LOS; days)	90 days from enrollment
Intensive care unit mortality	From randomization until date of death if occurred prior to discharge from the sentinel intensive care unit admission, assessed up to 52 weeks	Mortality during intensive care unit stay during sentinel admission

Trial Locations

Locations (1)

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States