Clinical trial NCT06966765: Accelerated vs Standard Approach to Continuous Veno-venous Hemodiafiltration Post-hemoperfusion (ASAP) in Severe Acute Diquat Poisoning
Official title: Accelerated vs Standard Approach to Continuous Veno-venous Hemodiafiltration Post-hemoperfusion (ASAP) in Severe Acute Diquat Poisoning: a Multi-center, Cluster, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Diquat Poisoning
Keywords: diquat
continuous kidney replacement therapy
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2025-05-13
Enrollment: 267
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: All-cause mortality rate
timeFrame: 90 days within the index date of randomization
measure: Time from exposure to death
timeFrame: 90 days within the index date of randomization
Secondary outcomes:
measure: ICU-free days
timeFrame: 90 days within the index date of randomization
measure: Ventilator-free days
timeFrame: 90 days within the index date of randomization
measure: Vasoactive-free days
timeFrame: 90 days within the index date of randomization
measure: CVVHDF dependence rate
timeFrame: 90 days within the index date of randomization
measure: Hospitalization-free days
timeFrame: 90 days within the index date of randomization
measure: Major adverse kidney events rate
timeFrame: 90 days within the index date of randomization
Other outcomes:
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