Serum Biomarkers to Predict Response to Angiotensin II in Septic Shock (DARK-Sepsis)
Septic Shock, Vasodilatory Shock
About this trial
This is an interventional treatment trial for Septic Shock focused on measuring septic shock, vasopressor, angiotensin II, renin, dipeptidyl peptidase 3 (DPP3), randomized controlled trial
Eligibility Criteria
Inclusion Criteria: Adult patients ≥18 years-old with persistent vasodilatory shock despite moderate-dose norepinephrine monotherapy, defined as those who require ≥0.1 mcg/kg/min for at least 30 minutes to maintain a MAP between 65-70 mmHg. 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. 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. 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. 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. Approval from the attending physician and clinical pharmacist conducting the study. Exclusion Criteria: Patients who are < 18 years of age. Patients diagnosed with acute occlusive coronary syndrome requiring intervention and/or cardiogenic shock. Patients with or suspected to have abdominal aortic aneurysm or aortic dissection. Acute stroke. Patients with acute mesenteric ischemia or those with a history of mesenteric ischemia. Patients with known Raynaud's phenomenon, systemic sclerosis, or vasospastic disease. Patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Patients with liver failure with a Model for End-Stage Liver Disease (MELD) score of =/>30. Patients with burns covering >20% of total body surface area. Patients with a history of asthma or chronic obstructive pulmonary disease (COPD) with active acute bronchospasm or (if not mechanically ventilated) with an acute exacerbation of their asthma/COPD requiring the use of inhaled bronchodilators. Patients requiring more than 500 mg daily of hydrocortisone or equivalent glucocorticoid medication as a standing dose. Patients with an absolute neutrophil count (ANC) of < 1,000/mm3 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. Patients with active bleeding AND hemoglobin < 7g/dL or any other condition that would contraindicate serial blood sampling. Untreated venous thromboembolism (VTE) or inability to tolerate pharmacologic VTE prophylaxis. Patients with a known allergy to mannitol. Patients with an expected survival of <24 hours, SOFA score ≥ 16, or death deemed to be imminent or inevitable during the admission. Either the attending physician or patient and/or substitute decisionmaker are not committed to all active treatment, e.g., do-not-resuscitate (DNR) status. 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. Prisoner status Patients who are currently participating in another interventional clinical trial.
Sites / Locations
- University of New Mexico Health Sciences CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
No Intervention
Angiotensin II
Standard of Care (SOC)
For patients randomized to the intervention group, once the dose of background norepinephrine reaches ≥0.10 mcg/kg/min for ≥30 minutes, angiotensin II will be started at a dose of 20 ng/kg/min (recommended starting dose in package insert).Thereafter, angiotensin II and norepinephrine will both be titrated to mean arterial pressure (MAP) goal of >/= 65 mmHg according to the protocol titration scheme and in accordance with the University of New Mexico Hospital (UNMH) Nursing Department Titration Guideline. Angiotensin II treatment will be capped at 72 hours, at which point (if a second vasopressor is still needed) the patient will be started on an alternative agent.
Vasopressor therapy be titrated by the clinical team per usual SOC and UNMH Nursing Department Titration Guideline. using other available vasopressor agents (e.g., higher-dose norepinephrine, vasopressin, epinephrine, phenylephrine, and/or dopamine). To provide a comparator arm, patients in the SOC will have renin and DPP3 levels obtained at equivalent timepoints.