The Efficacy of Initial Hemopurification Strategy for Acute Paraquat Poisoning in Adults: Study Protocol for a Randomized Controlled Trial (HeSAPP)
Phase: NA
Conditions: Poisoning
Sponsor: Peking Union Medical College Hospital

The Efficacy of Initial Hemopurification Strategy for Acute 
Paraquat Poisoning in Adults: Study Protocol for a Randomized 
Controlled Trial (HeSAPP) 
2018-4-6 
NCT03314909 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
PROTOCOL 
Study setting 
Patient recruitment would be completed in The First Affiliated Hospital of Zhengzhou 
University, a comprehensive tertiary medical center in Henan Province, China with 50 beds in 
emergency intensive care units (EICU). The estimated number of admitted acute paraquat 
poisoned patients ranges from 50-200 persons per year. To assist participant enrolment, after 
acceptance of this protocol, a notice of this trial would be sent to the Emergency Room (ER) 
of all secondary hospitals in Henan Province to improve transference to the First Affiliated 
Hospital of Zhengzhou University. Considering the fact that intervention would be 
administered in ER setting, and the relatively short duration of assigned hemopurification, 
adherence of patients is promising. Patients’ families would receive full explanation of 
treatment plan and continuous follow-up in order to promote adherence.  
 
Study population 
Upon admission to ER, patients suspected with PQ intoxication would receive a urine 
dithionite test, and only those with a positive result would be invited to participate in this trial. 
The urine dithionite test would be measured by Spectrophotometer Type 721, and the 
minimal measurable concentration of paraquat is 0.2 μg/ml. Detailed inclusion and exclusion 
criteria are listed as follows.  
Inclusion criteria 
Patients meeting with all of the following criteria would be included in this trial: (1) Suspected 
paraquat ingestion history (intended or accidental), which is confirmed by positive urine 
dithionite result (light blue, navy blue and dark blue). (2) Arriving at the ER within 24 hours 
after PQ digestion. (3) Age: 18 ~-70 years old. (4) No known current pregnancy or lactation. 
(4) Absence of cardiac arrest after poisoning, and no previous or present history of chronic 
kidney disease, chronic liver disease, respiratory failure, COPD, asthma, heart failure, 
pancreatic disease, acute coronary syndrome (ACS) or stoke. (5) No known combined 
ingestion with other poisons or alcohol. (6) No previous blood purification treatment prior to 
admission. (8) No known participation in other medical trials. (9) Agreement on informed 
consent. 
 
Exclusion criteria 
Patients in any one of the following conditions would be excluded: (1) Patients who are unable 
to comply with the procedures of the present trial, including those who change therapy or 
withdraw treatment. (2) Patients who develop severe allergic response to HP materials. (3) 
Patients who do not receive intervention within 4 hours after admission in reality. 
 

 
 
Allocation randomization and concealment 
All participants would be randomly stratified into three blocks according to the result of urine 
dithionite test, i.e. light blue, navy blue and dark blue. Block length is set at 12. With the help 
of SAS 9.3, patients in different blocks would be allocated to four groups, namely the 
hemodialysis group (HD group), hemoperfusion group (HP group), concurrent hemodialysis 
and hemoperfusion group (HP-HD group), and conservative therapy group (control group), 
at a 1:1:1:1 ratio(Figure 1). 
Due to the apparently different equipment of the interventions, it would be impractical to 
blind the present trial, therefore both patients and physicians would be aware of the exact 
treatment that the patients would receive. A sealed envelope with the allocation information 
would then be sent to the physician in charge of the patient after stratified grouping. To 
reduce assessor bias, blood samples and chest radiograph would be collected and examined 
by staff independent of this study.  
 
Intervention 
The intervention under investigation includes conservative therapy, hemoperfusion alone, 
hemodialysis alone, and hemoperfusion and hemodialysis concurrent therapy under the 
Guideline of Chinese Blood Purification for Acute Paraquat Poisoning Patients.  
 
Study procedure 
Physicians involved in the study would receive standardized training in carrying out this trial. 
Upon enrollment, informed consent, basic demographic information and collateral history 
would be taken from the patients or their next of kin (Table 1). PQ ingestion volume would 
be estimated as follows: 1 mouthful of liquid for women= 22 ml and 1 mouthful for men =28 
ml . PQ ingestion amount, defined as PQ concentration × PQ ingestion volume, would be 
calculated. Physicians would also assess the participants by various scores (Table 2), including 
Acute Physiologic and Chronic Health Evaluation (APACHE II) score and Poisoning Severity 
Score (PSS).  
 
Upon suspected diagnosis of PQ poisoning, all patients would receive gastric lavage with 
room warm water (≥5L), and 1g/kg active charcoal via nasogastric tube. After confirmed 
diagnosis by urine dithionite test, intervention would be initiated upon acquisition of informed 
consent and randomized allocation, which would take less 1 h after admission ideally. 
Subsequent treatment varies by groups: 
(1) HD group: participants would receive 4 hours of HD therapy a day for three 
consecutive days.  
(2) HP group: participants would receive 4 hours of HP a day for three consecutive days.  

(3) HP-HD group: participants in this group would receive 4 hours’ hemoperfusion and 
hemodialysis concurrent therapy for consecutively three days.  
(4) Control group: participants in this group would receive conservative treatment (see 
below). 
According to the Chinese Guideline on Management of Paraquat Poisoning, all patients 
groups would receive standard treatment as follow. Methylprednisolone 15mg/kg/d together 
with cyclophosphamide 15mg/kg/d would be administered for the first week. After the first 
week, methylprednisolone would be reduced by 40 mg every 3 days, while no more 
cyclophosphamide would be given. Patients would be given supplemental oxygen only if their 
PaO2 falls below 40mmHg or in the cases of Acute Respiratory Dyspnea Syndrome (ARDS).  
 
Procedure of HD 
(1) Preparation: Place a dual-lumen catheter in the internal jugular vein, or place a dual-
lumen catheter in the femoral vein if needed. Equip the hemodialysis machine (HD 
machine: Fresenius 4008s. Cartridge: Fresenius Fx60. Both by Fresenius Medical Care AG 
Co, Germany). Rinse the pipeline with 1L of normal saline (NS) at a speed of 100 ml/min. 
Set the volume of dialysis at 300 ml, and run the dialysis machine in close loop for 10 
min.  
(2) Anticoagulation: Inject 60-80 IU/kg low molecular weight heparin (LMWH) 20-30 min 
before hemodialysis. 
(3) Therapy and surveillance: connect the pipeline to the catheter, and run the dialysis 
machine at a speed (ml/min) 4 times as the patient’s weight (kg). Dialysis solution 
speed should be set at 500 ml/min. Run hemodialysis for 4 hours meanwhile closely 
monitor the patients’ vital signs. During HD, anticoagulation function should be 
monitored by transmembrane pressure (TMP) of dialyzer. If TMP > 250mmHg, 
additional LMWH should be added. 
 
Procedure of HP 
(1) Preparation: Establish a dual-lumen catheter in the internal jugular vein, or in the femoral vein 
if needed. Equip the hemoperfusion machine (HP machines: Jafron model JF-800. Cartridge: 
HA330. Both by Jafron biomedical.co.). Rinse the whole pipeline with 5% glucose solution at 
a speed of 100 ml/min until the pipeline is filled with glucose solution. Then rinse pipeline 
with NS at a speed of 200 ml/min. The total volume used for rinsing is 2000 ml. 
(2) Anticoagulation: Rinse the pipeline with 500ml NS mixed with 4 mg/dl heparin. Ten minutes 
later, rinse the pipeline with 300 ml NS. Connect the pipeline to the catheter on the patient. 
Inject 0.5-1.0 mg/kg heparin, then add heparin at a speed of 10-20 mg/h based on coagulation 
status (keep activated partial thromboplastin time (APTT) 50% above upper limit of normal). 
Stop adding heparin 30 min before the end of each course.  
(3) Surveillance: Run HP for 4 hours a day. Monitor vital signs during HP and prevent 
hypotension. Optimal flow velocity of extracorporeal blood flow ranges from 100 to 200 
ml/min. Change the hemoperfusion cartridge as soon as any charcoal appears in the blood 
flow. 

 
 
Procedure of HP-HD 
 
(1) Preparation: Place a dual-lumen catheter in the internal jugular vein, or in the femoral 
vein if needed in ER. Equip the blood purification machines (HP and HD machines and 
cartridges as mentioned above). The outlet of the HP cartridge should be connected 
with the inlet of HD machine. Rinse HP pipeline and HD pipeline with 1L of NS mixed 
with 3000 IU heparin at a speed of 100-150 ml/min, followed by 600ml of NS 
containing 3000 IU heparin. 
(2) Anticoagulation: Inject LMWH 50-60 IU/kg as loading dose, then maintain at a speed of 
400 IU/h and adjust dose according to transmembrane pressure (keep TMP≤
250mmHg). 
(3) Run HP-HD: Connect the inlet of the HP cartridge to the catheter, and run the machine 
for 4 hours. Blood flow speed ranges from 100 to 200 ml/min. Dialysis solution speed is 
500 ml/min. Hemoperfusion cartridge should be changed as soon as any charcoal 
appears. Patients’ virtual signs should be monitored during treatment. 
 
Monitoring 
Arterial blood gas test, complete blood count, coagulation function test, liver function, 
pancreatic function would be performed and urine volume would be taken every day before 
hemopurification (if there is any). Urine dithionite test result would be recorded every 4-6 
hours from admission until there are three consecutive negative results. Renal function would 
be tested daily. Chest radiographs would be taken once a week or as soon as the patient 
deteriorates. If any patient develops fever or sepsis during treatment, they would be 
investigated to identify potential catheter-related bloodstream infection. Ultrasound for lower 
limb deep veins would be administered for patients with notable increase of calf/thigh 
circumference to identify thrombogenesis.