Pilot RCT of Angiotensin II vs. Vasopressin in Septic Shock

• Status: Not yet recruiting
• Trial end date: 2022-11-30
• Target enrollment: 0
• Participant gender: All

Summary

This will be a randomized controlled unblinded pragmatic single-center pilot trial of the use of vasopressin vs. angiotensin II as a second-line vasopressor in patients with septic shock and persistent hypotension despite moderate-to-high doses of norepinephrine.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of New Mexico
• Collaborators: La Jolla Pharmaceutical Company; National Center for Advancing Translational Science (NCATS)
• Treatments: Angiotensin II; Angiotensinogen; Arginine Vasopressin; Giapreza; Vasopressins

Criteria

Inclusion Criteria:

• 1. Adult patients ≥18 years-old with vasodilatory shock refractory to norepinephrine monotherapy, defined as those who require ≥0.2 mcg/kg/min to maintain a MAP between 65-70 mmHg. Patients will be screened once they require ≥0.1 mcg/kg/min of norepinephrine and, if eligible, may be consented at this point. Study drug (angiotensin II or vasopressin) will be initiated once norepinephrine dose reaches ≥0.2 mcg/kg/min for at least 30 minutes.

• 2. Patients are required to have central venous and arterial catheters present, and they are expected to remain in place for at least the initial 72 hours of study.

• 3. Patients are required to have an indwelling urinary catheter present, and it is expected to remain in place for at least the 72 hours of study.

• 4. Patients must have received 20-30 mL/kg of crystalloid over the previous 24-hour period, as clinically appropriate, and no longer be fluid responsive as per UNMH protocol. By UNMH protocol, lack of fluid responsiveness is considered a failure to increase stroke volume, stroke volume index, cardiac output, or cardiac index (typically measured by non-calibrated pulse contour analysis using a FloTrac device) by at least 10% after a 500-mL crystalloid bolus or a passive leg raise. Patients for whom the treating physicians feel that 20 mL/kg of crystalloid may be clinically inappropriate can qualify for the study if the reason for withholding further IV fluids is documented.

• 5. Patient or (in patients unable to consent) legal authorized representative (LAR) is willing and able to provide written informed consent and comply with all protocol requirements.

• 6. Approval from the attending physician and clinical pharmacist conducting the study.

Exclusion Criteria:

• 1. Patients who are < 18 years of age.

• 2. Patients diagnosed with acute occlusive coronary syndrome requiring intervention and/or cardiogenic shock.

• 3. Patients with or suspected to have abdominal aortic aneurysm or aortic dissection.

• 4. Acute stroke.

• 5. Patients with acute mesenteric ischemia or those with a history of mesenteric ischemia.

• 6. Patients with known Raynaud's phenomenon, systemic sclerosis, or vasospastic disease.

• 7. Patients on veno-arterial (VA) ECMO.

• 8. Patients with liver failure with a Model for End-Stage Liver Disease (MELD) score of ≥30.

• 9. Patients with burns covering >20% of total body surface area.

• 10. Patients with a history of asthma or COPD with active acute bronchospasm or (if not mechanically ventilated) with an acute exacerbation of their asthma/COPD requiring the use of inhaled bronchodilators.

• 11. Patients requiring more than 500 mg daily of hydrocortisone or equivalent glucocorticoid medication as a standing dose.

• 12 Patients with an absolute neutrophil count (ANC) of < 1,000/mm3.

• 13. Patients with hemorrhagic shock OR active bleeding AND an anticipated need (within 48 hours of initiation of the study) for transfusion of >4 units of packed red blood cells.

• 14. Patients with active bleeding AND hemoglobin < 7g/dL or any other condition that would contraindicate serial blood sampling.

• 15. Untreated venous thromboembolism (VTE) or inability to tolerate pharmacologic VTE prophylaxis.

• 16. Patients with a known allergy to mannitol.

• 17. Patients with an expected survival of <24 hours, SOFA score ≥ 16, or death deemed to be imminent or inevitable during the admission

• 18. Either the attending physician or patient and/or substitute decision-maker are not committed to all active treatment (e.g., DNR status).

• 19. Patients who are known to be pregnant at the time of screening. [All women ≤50 years-old will need a negative serum pregnancy test (serum quantitative beta-hCG) to enroll.]

• 20. Prisoner status

• 21. Patients who are current participating in another interventional clinical trial.