Vasodilatory Shock
Conditions
Keywords
Vasodilatory shock, Angiotensin II, Pediatric Critical Care Medicine
Brief summary
The goal of this clinical trial is to determine the safety and efficacy of Angiotensin-II in the treatment of pediatric patients in fluid refractory vasodilatory shock. The main questions it aims to answer are: * To evaluate the change in blood pressure or reduction of vasoactive requirements (norepinephrine equivalent dosing) after initiating Angiotensin II * To establish the safety and tolerability of Angiotensin-II in pediatric patients Participants will receive Angiotensin-II in addition to standard of care therapy for vasodilatory shock. * The study team will then monitor the patient's vital signs, blood work, and for any potential side effects from the drug. * An ultrasound will be performed to look at blood flow through the kidney in the setting of vasodilatory shock. * A follow up phone call to check in with the patient will be performed 28 days after enrollment.
Interventions
DRUGAngiotensin-II
Angiotensin-II will be given per the titration protocol.
Sponsors
Innoviva Specialty Therapeutics
Todd Sweberg
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Days to 18 Years
Healthy volunteers
No
Inclusion criteria
* Pediatric patients less than 18 years of age who have received at least 40 mL/kg of crystalloid or colloid equivalent fluid resuscitation for vasodilatory shock * Titration of standard of care vasoactive medications for a minimum of 2 hours with persistent refractory hypotension for age, and who require a total sum NE equivalent dose of \> 0.1 μg/kg/min for a minimum of 1 hours and a maximum of 24 hours prior to initiation of Angiotensin-II. * Indwelling arterial and central venous lines. * Parent or legal guardian is willing and able to provide informed consent and assist the patient in complying with all protocol requirements.
Exclusion criteria
* Standing DNR/DNI order * Alternative shock diagnosis i.e. cardiogenic shock or post cardiac surgery * Cannulated to extracorporeal membrane oxygenation * Pre-existing condition confounding outcome determination such as terminal illness * Patients diagnosed with acute occlusive coronary syndrome requiring pending intervention. * Patients who have a history of asthma or are currently experiencing bronchospasm requiring the use of inhaled bronchodilators and who are not mechanically ventilated. * Patients with acute mesenteric ischemia or a history of mesenteric ischemia. * Patients with active bleeding AND an anticipated need of multiple transfusions (within 48 hours of Screening). * Patients with active bleeding, hemoglobin \< 7 g/dL, or any other condition that would contraindicate serial blood sampling. * Patients requiring more than 5 mg/kg daily of hydrocortisone or equivalent glucocorticoid medication as a standing dose. * Patients with an expected lifespan of \< 12 hours or withdrawal of life support within 24 hours of screening. * Patients currently using an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. * Patients with a known allergy to mannitol. * Patients who are currently participating in another investigational clinical trial. * Patients of childbearing potential who are known to be pregnant at the time of screening. * Prisoners * Patient's with Raynaud phenomenon, systemic sclerosis, or vasospastic disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients who have improvement in mean arterial pressure or reduction in sum norepinephrine equivalent at Hour 2 after the start of Synthetic Angiotensin-II | From enrollment to Hour 2 | Percentage (%) of patients who have improvement in mean arterial pressure (MAP, mmHg) or reduction in sum norepinephrine (NE) equivalent at Hour 2 after the start of Synthetic Angiotensin-II |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in systolic blood pressure | From enrollment to 24 hours | Change in systolic blood pressure (mmHg) from baseline to 24 hours |
| Change in diastolic blood pressure | From enrollment to 24 hours | Change in diastolic blood pressure (mmHg) from baseline to 24 hours |
| Change in concentration of serum lactate | From enrollment to 24 hours | Change in concentration of serum lactate (mmol/L) from baseline to 2 hours |
| Change in MAP | From enrollment to 24 hours | Change in mean arterial pressure (mmHg) from baseline to 24 hours |
| Change in PRSIM-III score | From enrollment to 24 hours | Change in PRSIM-III score from screening to 24 hours (%) |
| Change in total neutrophil count | From enrollment to 24 hours | Change in total neutrophil count (cells/µL) from the start of Synthetic Angiotensin-II to 24 hours |
| Change in renal resistive index (%) | From enrollment to 24 hours | Change in renal resistive index (%) from the start of Synthetic Angiotensin-II to 24 hours after the start of Synthetic Angiotensin-II |
| Change in pSOFA score | From enrollment to 24 hours | Change in pSOFA score from screening to 24 hours (%) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in in serum cytokine levels | From enrollment to Day 28 | Change in in serum cytokine levels over time (pg/dL) |
| Change in renal resistive index (%) over time | From enrollment to 28 days | Change in renal resistive index (%) over time |
| Change in tissue oxygenation over 2 hours | From enrollment to Hour 2 | Change in tissue oxygenation as defined by peripheral oxygen saturation (%) from baseline to 2 hours |
| Change in power doppler by point of care ultrasound assessment | From enrollment to 28 days | Change in power doppler by point of care ultrasound assessment (AU) |
| Change in renal blood flow over time | From enrollment to 28 days | Change in renal blood flow (mL/min) over time |
| Change in tissue oxygenation over 24 hours | From enrollment to Hour 24 | Change in tissue oxygenation as defined by peripheral oxygen saturation (%) from baseline to 24 hours |
| Change in heart rate | From enrollment to Hour 2 | Change in heart rate (beats per minute) from baseline to 2 hours |
| Change in sum norepinephrine equivalent dose over 24 hours | From enrollment to 24 hours | Change in sum norepinephrine equivalent dose (μg/kg/min) from baseline to 24 hours |
| 28-day all-cause mortality | From enrollment to Day 28 | 28-day all-cause mortality (%) |
| Number of ventilator days | From enrollment to Day 28 | Number of ventilator days |
| Ventilator free days | From enrollment to Day 28 | Number of ventilator free days |
| Days on vasoactive support | From enrollment to Day 28 | Number of days on vasoactive support |
| Change in T cell cell count | From enrollment to Day 28 | Change in T cell cell count (cells/µL) |
Countries
United States
Outcome results
None listed