Pragmatic trial of midodrine as a vasopressor-sparing agent in septic shock

/ABSTRACT The objective of this study is to conduct a pragmatic, randomized clinical trial to evaluate the effectiveness and safety of oral midodrine in patients with sepsis associated hypotension. This patient-centered study approach is seeking alternatives to minimize the burden of intensive care unit (ICU) stay in these patients. Sepsis is one of the leading causes of death and disability worldwide. Cardiovascular compromise in sepsis manifests as hypotension due to arterial vasodilation. Hypotension often persists despite initial fluid resuscitation, prompting additional fluid boluses and subsequent administration of intravenous vasopressor agents. Although peripheral intravenous access could be used to initiate vasopressor treatment, the need for close blood pressure monitoring requires ICU admission and, for any but very short-term use, arterial and central venous catheter placement. Both excess intravenous fluid and arterial and venous catheterization may expose the patients to risks, unintended harms and discomfort. Moreover, a persistent need for intravenous vasopressor infusion prolongs ICU stay with associated burdens and cost. Midodrine is an oral vasopressor agent originally approved for use to treat orthostatic hypotension. Observational studies have suggested increasing off-label use of oral midodrine as a vasopressor-sparing agent in various groups of critically ill patients. Randomized controlled trials showed mixed results likely due to the heterogeneous general ICU patient population. Our preliminary data and the existing evidence point to clear equipoise and the need for conducting the proposed pragmatic single-blinded randomized clinical trial to evaluate both the safety and effectiveness of midodrine for sepsis associated hypotension. Our hypothesis is that administering oral midodrine to patients with septic shock who have received initial fluid resuscitation, appropriate antimicrobial treatment, and source control will decrease the duration of intravenous vasopressor treatment. If efficacious, midodrine can facilitate less invasive sepsis treatment and decrease the burdens and cost of ICU stay. Project Number: 1R61HL177037-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: OGNJEN GAJIC | Institution: MAYO CLINIC ROCHESTER, ROCHESTER, MN | Award Amount: $783,661 | Activity Code: R61 | Study Section: NHLBI Single-Site and Pilot Clinical Trials Study Section[SSPT (MA)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R61HL17703701A1