Vasopressin for Septic Shock Pragmatic Trial (VASSPR)

Life-threatening low blood pressure due to a serious infection is called "septic shock." Septic shock is treated with vasopressors, medications that raise blood pressure. Sometimes first-line vasopressors are inadequate, prompting addition of a second-line vasopressor called vasopressin. However, the threshold at which to start vasopressin remains unclear. This pragmatic, cluster-randomized, cluster-crossover trial will evaluate two different strategies for septic shock treatment commonly used in current practice, comparing a lower versus a higher threshold for adding vasopressin to first-line vasopressors.

Study Overview

• Status: Enrolling by invitation
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Vasopressin; Other: Recommendation to use a lower initiation threshold for vasopressin; Other: Recommendation to use a higher initiation threshold for vasopressin

• Study Type: Interventional
• Enrollment (Estimated): 2050
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Idaho
    • Burley, Idaho, United States, 83318
      • Cassia Regional Hospital
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
    • Cedar City, Utah, United States, 84721
      • Cedar City Hospital
    • Layton, Utah, United States, 84041
      • Layton Hospital
    • Logan, Utah, United States, 84341
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital
    • Park City, Utah, United States, 84060
      • Park City Hospital
    • Provo, Utah, United States, 84604
      • Utah Valley Hospital
    • Riverton, Utah, United States, 84065
      • Riverton Hospital
    • Saint George, Utah, United States, 84790
      • St. George Regional Hospital
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Sandy, Utah, United States, 84094
      • Alta View Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years
2. Admitted to a study hospital emergency department (ED) or inpatient care unit
3. Administration of vasopressor(s) for septic shock

Exclusion Criteria: None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Septic shock treatment strategy involving a lower threshold for vasopressin initiation; Recommended strategy for treatment of septic shock includes initiation of fixed-dose IV vasopressin (1.8 units/hour) as a second-line vasopressor if the combined norepinephrine-equivalent dose of other vasopressors reaches ≥0.1 micrograms/kilogram/minute (mcg/kg/min). Use of the recommended treatment strategy (via entry of an order for threshold-based vasopressin initiation) or an alternative treatment strategy is at the discretion of patients' treating clinical team.	Drug: Vasopressin; Intravenous vasopressin infusion added to first-line vasopressors. Recommended vasopressin dose is 1.8 units/hour (equivalent to 0.03 units/minute) at a fixed rate.; Other: Recommendation to use a lower initiation threshold for vasopressin; Recommended to initiate intravenous vasopressin infusion if the combined dose of other vasopressors reaches ≥0.1 mcg/kg/min of norepinephrine (or equivalent)
Active Comparator: Septic shock treatment strategy involving a higher threshold for vasopressin initiation; Recommended strategy for treatment of septic shock includes initiation of fixed-dose IV vasopressin (1.8 units/hour) as a second-line vasopressor if the combined norepinephrine-equivalent dose of other vasopressors reaches ≥0.4 mcg/kg/min. Use of the recommended treatment strategy (via entry of an order for threshold-based vasopressin initiation) or an alternative treatment strategy is at the discretion of patients' treating clinical team.	Drug: Vasopressin; Intravenous vasopressin infusion added to first-line vasopressors. Recommended vasopressin dose is 1.8 units/hour (equivalent to 0.03 units/minute) at a fixed rate.; Other: Recommendation to use a higher initiation threshold for vasopressin; Recommended to initiate intravenous vasopressin infusion if the combined dose of other vasopressors reaches ≥0.4 mcg/kg/min of norepinephrine (or equivalent)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day all-cause mortality	Death on or before study day 28	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal replacement therapy-free days to day 28	Number of days between day 28 and the end of the last period of renal replacement therapy prior to day 28. Death on or before day 28 will be assigned a value of -1. For patients with baseline end-stage renal failure on dialysis prior to the index hospitalization, potential values for this ordinal outcome will be 0 or -1.	28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-hospital all-cause mortality	Death prior to discharge from the hospital	From onset of septic shock to hospital discharge, an average of 10 days
90-day all-cause mortality	Death on or before study day 90	90 days
Vasopressor-free days to day 28	Number of days between day 28 and the end of the last period of vasopressor therapy prior to day 28. Death on or before day 28 will be assigned a value of -1.	28 days
Incidence of new renal replacement therapy	New receipt of renal replacement therapy after onset of septic shock. Patients receiving renal replacement therapy prior to enrollment are excluded from this outcome.	From onset of septic shock until hospital discharge, an average of 10 days
Intensive care unit-free days to day 28	Number of days between day 28 and the end of the last period of intensive care unit admission prior to day 28. Death on or before day 28 will be assigned a value of -1.	28 days
Hospital-free days to day 28	Number of days between day 28 and the end of the last period of hospital admission prior to day 28. Death on or before day 28 will be assigned a value of -1.	28 days
Incidence of acute coronary syndrome	Documented new-onset clinical diagnosis of acute coronary syndrome or myocardial infarction	From onset of septic shock until hospital discharge, an average of 10 days
Incidence of mesenteric ischemia	Documented new-onset clinical diagnosis of mesenteric ischemia	From onset of septic shock until hospital discharge, an average of 10 days
Incidence of soft tissue ischemia	Documented new-onset clinical diagnosis of extremity, nose, or ear ischemia	From onset of septic shock until hospital discharge, an average of 10 days
Incidence of vasopressor extravasation	Documented clinical diagnosis of vasopressor extravasation	From onset of septic shock until hospital discharge, an average of 10 days
Incidence of clinically-significant arrhythmia	Documented clinical diagnosis of clinically-significant arrhythmia (sustained ventricular tachycardia, reentrant [supraventricular] tachycardia, atrial arrhythmia with rapid ventricular response requiring intervention, or new-onset atrial fibrillation or flutter)	From onset of septic shock until hospital discharge, an average of 10 days
Incidence of cardiogenic shock	Documented clinical diagnosis of cardiogenic shock	From onset of septic shock until hospital discharge, an average of 10 days
Incidence of cardiac arrest	Documented occurrence of a cardiac arrest with administration of chest compressions or defibrillation	From onset of septic shock until hospital discharge, an average of 10 days
Incidence of severe hyponatremia	New-onset severe hyponatremia (serum sodium <120 milliequivalents/liter)	From onset of septic shock until hospital discharge, an average of 10 days
Maximum lactate	Maximum lactate value (millimoles/liter) from enrollment through study day 7	7 days
Incidence of abnormal troponin	Serum troponin above the upper limit of normal for assay in interval from enrollment through study day 7	7 days

Collaborators and Investigators

• Sponsor: Intermountain Health Care, Inc.
• Collaborators: University of Utah
• Investigators: Principal Investigator: Ithan Peltan, MD, MSc, Intermountain Health

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: January 18, 2024
• First Posted (Actual): January 22, 2024

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Vasopressin; Vasopressors; Treatment strategy
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Natriuretic Agents; Hemostatics; Coagulants; Vasoconstrictor Agents; Antidiuretic Agents; Vasopressins; Arginine Vasopressin
• Other Study ID Numbers: 1052518

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In order to protect patient privacy and comply with relevant regulations, identified data will be unavailable. Requests for deidentified data from qualified researchers with appropriate ethics board approvals and relevant data use agreements will be processed by the Intermountain Office of Research, officeofresearch@imail.org.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No