Midodrine Use in Septic Shock

University of Virginia

Status and phase: Terminated; Phase 3

Conditions: Septic Shock

Treatments: Other: placebo; Drug: Midodrine Hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT03706053

20889

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 89 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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10 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Investigational pharmacy formulated placebo. In early phase patients will be randomized to placebo, 10mg TID midodrine or 20 mg TID midodrine. (15 per group)

Treatment:

Other: placebo

Midodrine Hydrochloride 10 mg TID

Experimental group

Description:

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).

Treatment:

Drug: Midodrine Hydrochloride

Midodrine Hydrochloride 20 mg TID

Experimental group

Description:

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).

Treatment:

Drug: Midodrine Hydrochloride