Synthetic Angiotensin II/Giapreza in Pediatric Patients With Refractory Hypotension

An Open-Label, Single-Center Study of Synthetic Angiotensin II/Giapreza in Pediatric Patients With Refractory Hypotension Despite Receiving Fluid Therapy and Vasoactive Therapy

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.

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.