Synthetic Angiotensin II/Giapreza in Pediatric Patients With Refractory Hypotension

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Angiotensin-II
  Angiotensin-II will be given per the titration protocol.

Первичные конечные точки

• 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 [Срок оценки: From enrollment to Hour 2]

Вторичные конечные точки (8)

• Change in MAP [Срок оценки: From enrollment to 24 hours]
• Change in systolic blood pressure [Срок оценки: From enrollment to 24 hours]
• Change in diastolic blood pressure [Срок оценки: From enrollment to 24 hours]
• Change in concentration of serum lactate [Срок оценки: From enrollment to 24 hours]
• Change in pSOFA score [Срок оценки: From enrollment to 24 hours]
• Change in PRSIM-III score [Срок оценки: From enrollment to 24 hours]
• Change in total neutrophil count [Срок оценки: From enrollment to 24 hours]
• Change in renal resistive index (%) [Срок оценки: From enrollment to 24 hours]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Cohen Children's Medical Center of Northwell Health — New Hyde Park
• Cohen Children's Medical Center — Queens

Публикации

• Bailey DM, Chima RS, Tidmarsh GF, Williams MD. Synthetic Human Angiotensin II in Pediatric Patients With Vasodilatory Shock: A Report on Two Patients. Crit Care Explor. 2019 Aug 15;1(8):e0036. doi: 10.1097/CCE.0000000000000036. eCollection 2019 Aug. PMID 32166277
• Tezel O, Hutson TK, Gist KM, Chima RS, Goldstein SL, Stanski NL. Utilization of Synthetic Human Angiotensin II for Catecholamine-Resistant Vasodilatory Shock in Critically Ill Children: A Single-Center Retrospective Case Series. Crit Care Explor. 2023 Sep 12;5(9):e0978. doi: 10.1097/CCE.0000000000000978. eCollection 2023 Sep. PMID 37711646
• Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hastbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM; ATHOS-3 Investigators. Angiotensin II for the Treatment of Vasodilatory Sho PMID 28528561

Идентификаторы

NCT: NCT07212686 · 24-0641-CCMC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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