Accelerated Versus Standard Initiation of Continuous Veno-Venous Hemodiafiltration Following Hemoperfusion in Severe Acute Diquat Poisoning

Nanjing University

Status and phase: Begins enrollment in 2 months; Phase 3

Conditions: Diquat Poisoning

Treatments: Procedure: Continuous Veno-Venous Hemodiafiltration

Study type: Interventional

Funder types: Other

Identifiers

NCT06966765

2025-12122-2

Details and patient eligibility

About

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 distributed to gastrointestinal tract, kidneys, liver, skeletal muscle, lungs, myocardium, and central nervous systems. Patients with severe diquat poisoning often develop toxic encephalopathy, circulatory collapse, and multi-organ dysfunction. Extracorporeal treatments, including hemoperfusion, hemodialysis, and continuous kidney replacement therapy (CKRT), are widely employed to manage diquat poisoning. Continuous veno-venous hemodiafiltration (CVVHDF), the most frequently used CKRT modality, is primarily indicated for acute kidney injury (AKI). AKI occurs in up to 73.3% of patients with acute diquat poisoning, and nearly all patients with severe acute diquat are at risk of developing AKI. 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 (ED). 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 yet to be evaluated in clinical trials. Currently, the standard practice delays initiation of CVVHDF until AKI has developed. Accordingly, this study proposes a pragmatic cluster-randomized controlled trial (RCT) to determine whether, in severe acute diquat poisoning patients, accelerated initiation of CVVHDF following hemoperfusion is preferred compared to a standard approach in which CVVHDF is initiated only in the presence of AKI or at the discretion of the treating clinician.

Enrollment: 267 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. Evidence of co-ingestion of other toxic substances alongside diquat; and/or
2. Withholding of CVVHDF due to limitations on the escalation of life-sustaining therapies; and/or
3. Any CKRT within the previous 2 months; and/or
4. Kidney transplant within the past 365 days; and/or
5. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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267 participants in 2 patient groups

Accelerated Initiation

Experimental group

Description:

Participants in this experimental arm will receive CVVHDF within 12 hours of eligibility confirmation. This 12-hour window includes the time required to obtain consent, place a dialysis catheter, and initiate CVVHDF.

Treatment:

Procedure: Continuous Veno-Venous Hemodiafiltration

Standard Initiation

Active Comparator group

Description:

Treating clinician(s) will not be encouraged to initiate CVVHDF unless the patient develops AKI, defined by any of the following criteria, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. CVVHDF may be initiated at any time at the discretion of the treating clinician(s). However, if CVVHDF is initiated without the participant meeting AKI diagnostic criteria, treating clinician(s) will be asked to document the primary rationale. Conversely, even when AKI criteria are met, there is no obligation to initiate CVVHDF if the treating clinician(s) judge that alternative medical interventions are more appropriate based on current standard care; in such cases, the reasons for withholding CVVHDF should also be documented.

Treatment:

Procedure: Continuous Veno-Venous Hemodiafiltration