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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Accelerated Initiation | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Continuous Veno-Venous Hemodiafiltration | Procedure | 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 goals of care with withdrawal of life-sustaining interventions; or (3) recovery of kidney function, as determined by treating clinician(s), such that CVVHDF will be no longer required. However, CVVHDF will be reinitiated at the discretion of treating clinician(s), if kidney function comes suboptimal after a period of discontinuation. |
| Measure | Description | Time Frame |
|---|---|---|
| All-cause mortality rate | 90 days within the index date of randomization | |
| Time from exposure to death | The primary outcome measure included time from exposure to death. | 90 days within the index date of randomization |
| Measure | Description | Time Frame |
|---|---|---|
| ICU-free days | 90 days within the index date of randomization | |
| Ventilator-free days | 90 days within the index date of randomization | |
| Vasoactive-free days |
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Inclusion criteria:
Exclusion criteria:
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| ID | Term |
|---|---|
| D000079664 | Continuous Renal Replacement Therapy |
| ID | Term |
|---|---|
| D017582 | Renal Replacement Therapy |
| D013812 | Therapeutics |
| D005112 | Extracorporeal Circulation |
| D013514 | Surgical Procedures, Operative |
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| 90 days within the index date of randomization |
| CVVHDF dependence rate | 90 days within the index date of randomization |
| Hospitalization-free days | 90 days within the index date of randomization |
| Major adverse kidney events rate | The secondary outcome measure included major adverse kidney events at 90 days after randomization, defined as the composite of death, CVVHDF dependence, or sustained reduction of kidney function (defined as eGFR <75% of the lowest eGFR measured during hospitalization). | 90 days within the index date of randomization |