Accelerated HEmodiafiltration in Severe Acute Diquat (AHEAD) Poisoning

Official title

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

Overview

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.

Interventions

• Procedure 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

Primary outcome measures

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

Secondary outcome measures (6)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07234383 · 2025-0919-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗