Accelerated HEmodiafiltration in Severe Acute Diquat (AHEAD) Poisoning

Официальное название

Accelerated HEmodiafiltration in Severe Acute Diquat (AHEAD) Poisoning: a Single-center, Single-arm, Open-label, Clinical Trial

Обзор

Diquat (1,1'-ethylene-2,2'-bipyridinium) is a bipyridine herbicide that shares a similar physicochemical structure and redox cycling mechanism with paraquat. Upon ingestion, it is rapidly absorbed and distributes widely, including gastrointestinal tract, kidneys, liver, skeletal muscle, lungs, myocardium, and central nervous system. Severe diquat poisoning commonly causes toxic encephalopathy, circulatory collapse, and multiorgan dysfunction. Extracorporeal treatments, including hemoperfusion, hemodialysis, and continuous kidney replacement therapy, are frequently used in management. Continuous veno-venous hemodiafiltration (CVVHDF), the most frequently used continuous kidney replacement therapy modality, is primarily indicated for acute kidney injury. Acute kidney injury occurs in up to 73.3% of patients with acute diquat poisoning, and nearly all patients with severe acute diquat poisoning are at risk of developing acute kidney injury. In clinical practice, patients with severe acute diquat poisoning are typically defined as those with a plasma diquat concentration of ≥1000 ng/mL measured at the time of presentation to the emergency department. However, the Extracorporeal Treatments in Poisoning (EXTRIP) workgroup has not issued any definitive recommendations on initiating extracorporeal treatments for diquat poisoning, and the optimal timing for starting CVVHDF has not been evaluated in clinical trials. Current practice typically delays CVVHDF until acute kidney injury occurs. A preliminary retrospective cohort study suggested that, among severe acute diquat poisoning patients treated with combined hemoperfusion and CVVHDF, an interval of \<30 minutes between hemoperfusion and CVVHDF was associated with a significantly lower risk of death compared with longer intervals (≥30 minutes). Accordingly, this study proposes a single-arm trial (SAT) to determine whether accelerated initiation of CVVHDF immediately following hemoperfusion improves outcomes in patients with severe acute diquat poisoning.

Вмешательства

• Процедура Continuous Veno-Venous Hemodiafiltration
  CVVHDF will be delivered following hemoperfusion with a dialysate-to-replacement fluid ratio maintained at 1:1, a blood flow rate of 150-200 mL/min, and a target dialysis dose of 30 mL/kg/h (excluding additional fluid removal). Regional anticoagulation (e.g., heparin or other agent per device requirements) will be used to prevent clotting within the circuit. Once CVVHDF is initiated in either arm, it will not be discontinued until one of the following encountered: (i) death; or (ii) a change in

Первичные конечные точки

• All-cause mortality rate [Срок оценки: 90 days within the index date of randomization]
• Time from exposure to death [Срок оценки: 90 days within the index date of randomization]

Вторичные конечные точки (6)

• ICU-free days [Срок оценки: 90 days within the index date of randomization]
• Ventilator-free days [Срок оценки: 90 days within the index date of randomization]
• Vasoactive-free days [Срок оценки: 90 days within the index date of randomization]
• CVVHDF dependence rate [Срок оценки: 90 days within the index date of randomization]
• Hospitalization-free days [Срок оценки: 90 days within the index date of randomization]
• Major adverse kidney events rate [Срок оценки: 90 days within the index date of randomization]

Критерии участия

Критерии включения

• Age ≥ 18 years; and
• A history of oral exposure to diquat solution, reported by patient(s) or their legal proxies; and
• An exposure time (time form exposure to presentation at ED) ≤ 48 hours, reported by patient(s) or their legal proxies; and
• Plasma diquat concentration measured upon ED presentation ≥ 1,000 ng/mL.

Критерии исключения

• Evidence of co-ingestion of other toxic substances alongside diquat; and/or
• Withholding of CVVHDF due to limitations on the escalation of life-sustaining therapies; and/or
• Any CKRT within the previous 2 months; and/or
• Kidney transplant within the past 365 days; and/or
• Known pre-hospitalization advanced chronic kidney disease, defined by an estimated glomerular filtration rate calculated using serum creatine (eGFRer) of less than 30 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, if pre-hospitalization serum creatine is available; and/or (6) Treating clinician(s) believe(s) that either immediate or deferral of CVVHDF initiation is mandated; and/or (7) Pregnant or breast feeding.

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

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07234383 · 2025-0919-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗