Vasopressin Timing for Septic Shock

(CASPER-Pilot Trial)

Overseen By Gretchen L. Sacha, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The Cleveland Clinic

Must be taking: Norepinephrine

Must not be taking: Other vasoactive agents

Disqualifiers: Vasopressin initiation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Duration of hospitalization

300 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot be on any other vasoactive agents besides norepinephrine when you join the study.

What data supports the effectiveness of the drug Vasopressin for septic shock?

Research shows that starting vasopressin early in septic shock can reduce the risk of organ failure and death in the hospital. It also helps stabilize blood pressure more effectively compared to using other drugs alone. ^{1 2 3 4 5}

Is vasopressin safe for use in humans?

Vasopressin is generally considered safe as a second-line treatment for septic shock, but its safety profile is not fully established, especially regarding its effects on organ function and interactions with other treatments. ^{1 2 5 6 7}

How does early vasopressin use differ from other treatments for septic shock?

Early use of vasopressin in septic shock is unique because it is initiated soon after the onset of shock, which may reduce organ failure and mortality compared to starting it later. This approach focuses on timing, as vasopressin is typically used as a second-line treatment after norepinephrine, but starting it earlier could improve outcomes. ^{1 2 5 8 9}

What is the purpose of this trial?

The goal of the CASPER-Pilot study is to develop clinical decision support (CDS) technology within Epic to randomize patients with septic shock to early versus standard of care vasopressin initiation. The primary aim of this study will be to test the hypothesis that CDS technology can be utilized to create two distinct cohorts of patients reflecting different times of vasopressin initiation based on norepinephrine dose requirements. Secondarily, this study will evaluate the proportion of patients whose norepinephrine dose at the time of vasopressin initiation is within the specified range for the intervention arm they were randomized to. Other outcomes of evaluation will include adherence to the developed CDS technology and comparison of clinical outcomes between the two treatment arms.

Research Team

Gretchen L. Sacha, PharmD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for patients with septic shock, a severe infection leading to dangerously low blood pressure. Participants must meet specific criteria not disclosed here.

Inclusion Criteria

I have been diagnosed with septic shock.

I am admitted to the Cleveland Clinic Main Campus Medical ICU.

I am on a continuous norepinephrine infusion at more than 5 mcg/min.

Exclusion Criteria

I am not taking any blood pressure medications other than norepinephrine.

I was given vasopressin for my condition before the study, with low NE levels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants are randomized to early or standard of care vasopressin initiation based on norepinephrine dose requirements

Duration of hospitalization

Continuous monitoring during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment

Through hospitalization admission

Outcome Evaluation

Evaluation of norepinephrine-equivalent dose, ICU mortality, in-hospital mortality, and hemodynamic response

6 hours to end of hospitalization

Treatment Details

Interventions

• Vasopressin

Trial Overview The study tests if clinical decision support technology can help start vasopressin treatment early versus the standard timing based on norepinephrine dose needs in septic shock patients.

Participant Groups

Group I: Early Vasopressin Initiation Experimental Treatment 1 Intervention

Patients randomized to this arm will have a provider BPA fire prompting vasopressin initiation when the norepinephrine dose is between 10-20 mcg/min

Group II: Standard of Care Vasopressin Initiation Active Control 1 Intervention

Patients randomized to this arm will have a provider BPA fire prompting vasopressin initiation when the norepinephrine dose is between 20-35 mcg/min

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

References

1. England pubmed.ncbi.nlm.nih.gov

Timing of vasopressin initiation and mortality in patients with septic shock: analysis of the MIMIC-III and MIMIC-IV databases. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

EARLY INITIATION OF VASOPRESSIN REDUCES ORGAN FAILURE AND MORTALITY IN SEPTIC SHOCK. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of continuous vasopressin infusion in patients with septic shock. [2004]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Efficiency of Vasopressin or Its Analogs in Comparison With Catecholamines Alone on Patients With Septic Shock: A Systematic Review and Meta-Analysis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The effect of early vasopressin use on patients with septic shock: A systematic review and meta-analysis. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Narrative Review of Controversies Involving Vasopressin Use in Septic Shock and Practical Considerations. [2020]

7. England pubmed.ncbi.nlm.nih.gov

The Vasopressin Loading for Refractory septic shock (VALOR) study: a prospective observational study. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Optimizing Vasopressin Use and Initiation Timing in Septic Shock: A Narrative Review. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Cytokines and signaling molecules predict clinical outcomes in sepsis. [2021]