Accelerated HEmodiafiltration in Severe Acute Diquat (AHEAD) Poisoning

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Diquat Poisoning
• Intervention / Treatment: Procedure: Continuous Veno-Venous Hemodiafiltration

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Accelerated Initiation; 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.

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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization-free days		90 days within the index date of randomization
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		90 days within the index date of randomization
CVVHDF dependence rate		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

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 24, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Surgical Procedures, Operative; Extracorporeal Circulation; Renal Replacement Therapy; Continuous Renal Replacement Therapy
• Other Study ID Numbers: 2025-0919-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No