Clinical trial NCT03129542: Midodrine Hydrochloride in Early Sepsis
Official title: Oral Midodrine Hydrochloride in Early Sepsis: Randomized, Double Blind and Placebo-Controlled Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sepsis
Blood Pressure
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Cleveland Clinic Abu Dhabi
First posted: 2017-04-26
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The Investigators propose a prospective, randomized, double blind, placebo-controlled pilot study on the efficacy and safety of midodrine in the treatment of sepsis.
Primary purpose: TREATMENT

Brief summary: The investigators would like to determine if early administration of oral Midodrine in participants diagnosed with sepsis will impact blood pressures and decrease the need for and/or doses of intravenous pressor agents.

Detailed description: Three doses of either placebo or midodrine every 8 hours will be administered in addition to usual care for sepsis. The goal will be to administer the first dose approximately within 24 hours of diagnosis. The first dose will be administered only after the patient has been admitted to the ICU. Subjects will receive treatment for a total of 16 hours starting from the first dose. The medical provider, nursing staff and patient will be blinded to randomization, only research pharmacist will be aware of randomization. Blood pressure will be recorded at least on a 4 hourly basis for 24 hours from the time of administration of the first dose, and also just prior to administration of each dose. Subsequent doses will be held if systolic blood pressure, SBP, is greater than 130 mmHg. If a subject requires initiation of intravenous vasopressor agents following study enrollment, subsequent doses will be continued. There will be no further intervention after all 3 doses have been administered; however clinical outcomes and adverse events will be monitored.

Eligibility criteria: Inclusion Criteria:

Patients diagnosed with sepsis based on the old Sepsis criteria and meeting all of the following criteria will be considered eligible to participate in the study.

* Age greater than or equal to 18 years
* Able to safely tolerate medication either by mouth or feeding tube (i.e. absence of nausea or vomiting)
* Able to give consent for participation or have representative available
* Two or more blood pressure readings taken at least 15 minutes apart with mean arterial pressures, MAPs 70 or less
* Treating consultant agrees to the study plan

Exclusion Criteria:

Patients meeting any one of the following criteria will be excluded from participation:

* Women of child bearing age with the potential to become pregnant who do not have a clinically documented negative pregnancy test
* Current cardiogenic shock or known systolic heart failure with left ventricular ejection fraction (LVEF) \< 30%
* Current bowel ischemia
* Recent Myocardial infarction within the past 3 months
* Current use of Monoamine Oxidase Inhibitors (MAOIs)
* Recent Stroke within the past 3 months
* Midodrine as a home medication
* Known allergy to Midodrine
* High dose vasopressor use (norepinephrine \>0.25 mcg/kg/min)
* Lactate more than 8 mmol/L
* Contraindications to use: History of pheochromocytoma or thyrotoxicosis or glaucoma or ischemic bowel disease

Primary outcomes:
measure: Duration of Vasopressor Use
timeFrame: 24 hours
Secondary outcomes:
measure: Mean arterial blood pressure (MAP)
timeFrame: 24 hours after the first drug dose
measure: Cumulative Fluid Balance
timeFrame: 24 hours after sepsis onset
measure: ICU and hospital length of stay, central venous access use and organ failure
timeFrame: The first 7 days of study enrollment or until discharge
measure: Incidence of potential side effects attributable to Midodrine
timeFrame: 48 hours after enrollment
measure: Cumulative Vasopressor Dose
timeFrame: 24 hours after the first drug dose
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Ognjen Gajic
role: PRINCIPAL_INVESTIGATOR
References: