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IRCT20260527069547N1 IRCT 2026-08-19 Islamic Azad University HA380 Hemoperfusion Effects in Septic Shock Effect of Early HA380 Hemoperfusion on Hemodynamic Recovery and Organ Dysfunction in Adult Patients with Septic Shock 2026-08-23 anticipated 38 Recruiting https://irct.ir/trial/90444 interventional Randomization: Randomized, Blinding: Not blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Other design features: 1. A deliberate enrichment strategy is employed, selecting patients with early, moderate septic shock (norepinephrine ≤ 0.2 mcg/kg/min and SOFA ≤ 7) per sponsor recommendation. This excludes patients with advanced, potentially irreversible organ failure who may not benefit from standalone hemoperfusion .2.Separation of Hemoperfusion from CRRT: Unlike other studies, HA380 is delivered via a standalone hemoperfusion machine, not integrated into a CRRT circuit. This avoids confounding from concurrent CRRT, enhances treatment standardization, and allows clean assessment of HA380 efficacy. CRRT may be initiated in both groups after the 3-day intervention period if clinically indicated. 3. Fixed-Duration Intervention: A fixed 3-day, 4-hour-per-session course is used rather than response-guided duration, enabling assessment of a cumulative effect while avoiding bias from clinician decisions to continue or stop therapy early. 4.Time-Window Design: Hemoperfusion must start within 6–8 hours of shock onset, rigorously defined, to maximize the chance of modulating the inflammatory response before irreversible organ failure occurs. 5.Multi-Timepoint Primary Endpoint with Day 3 Focus: SOFA change is measured at Days 1, 3, and 7 and analyzed using a mixed model for repeated measures. Day 3 (72 hours) is the principal time point of interest, immediately after the 3-day hemoperfusion course and before hospital-acquired infections become a major confounder. 6.Competing Risk Handling: To address the competing risk of death, deceased patients are assigned the maximum SOFA score (24) for subsequent time points. Survival and composite outcome sensitivity analyses are pre-specified. 7.Statistician Blinding: Despite the open-label design, the study statistician performing primary and final analyses remains blinded to group allocation (groups coded as A/B) until the statistical analysis plan is finalized and analyses are complete, Randomization description: Randomization Method: Permuted block randomization with randomly varying block sizes of 4 or 6 will be used to ensure balanced allocation between the two groups. Allocation Ratio: 1:1 (intervention : control). Allocation Concealment: The randomization sequence will be generated by an independent statistician (not involved in screening, enrollment, or treatment) using statistical software. Allocation codes will be placed in sequentially numbered, opaque, sealed envelopes (SNOSE). Envelopes will be opened by the principal investigator only after informed consent is obtained. Sequence Generation: A random number sequence will be generated using statistical software (e.g., Stata, R, or SAS) with a random seed. Documentation: The randomization list will be kept by the independent statistician and will not be accessible to the clinical research team until data collection and database lock are completed. N/A Septic Shock. Intervention 1: Intervention group: Patients randomized to the intervention group will receive standard sepsis care plus hemoperfusion with the HA380 cartridge (Jafron Biomedical, China). The intervention specifications are as follows:Timing of Initiation:Hemoperfusion will be initiated within 12 hours of septic shock diagnosis. Shock onset is defined as the time vasopressor infusion (norepinephrine) is started at ≥ 0.1 µg/kg/min in the presence of serum lactate ≥ 2 mmol/L and persistent hypotension despite adequate fluid resuscitation.Mode of Delivery:Hemoperfusion will be performed using a standalone hemoperfusion machine, not integrated into a CRRT circuit. This approach is chosen to enhance treatment consistency and avoid potential confounding from CRRT-related factors. If the patient has no indication for CRRT at enrollment, they will receive standalone hemoperfusion only.Technical Specifications:Cartridge: HA380Blood flow rate: 150–200 mL/minDuration per session: 4 hoursFrequency: Once daily for 3 consecutive days (total of 3 sessions)Vascular Access:A double-lumen central venous catheter (minimum 12 Fr) inserted into the femoral or internal jugular vein.Anticoagulation:Systemic unfractionated heparin according to the ICU standard protocol (target activated partial thromboplastin time: 1.5–2.0 times normal).CRRT After Hemoperfusion:After completion of the 3 HA380 hemoperfusion sessions, if the patient's condition deteriorates and clinical indications for CRRT develop (refractory oliguria, severe metabolic acidosis, refractory hyperkalemia, or fluid overload unresponsive to diuretics), the patient in the intervention group may receive CRRT at the discretion of the treating ICU physician. This decision will be documented in the medical record. Intervention 2: Control group: The control group will receive standard septic shock management according to the Surviving Sepsis Campaign international guidelines. CRRT may be initiated at any time if clinically indicated, at the discretion of the treating physician. Undecided - It is not yet known if there will be a plan to make this available Justification or reason for indecision in sharing IPD is De-identified individual participant data will be available upon reasonable request from the corresponding author after publication of the main study results, subject to ethical considerations and approval by the ethics committee. The final decision regarding public data sharing in open-access repositories will be made after consultation with the ethics committee and the research team.
public Amir Saeed
Ferdowsi Ave
Urmia Iran (Islamic Republic of) 1513846911 +98 44 3101 0000 dr.saeedamir@yahoo.com Islamic Azad University scientific Amir Saeed
Ferdowsi Ave
Urmia Iran (Islamic Republic of) 5719151193 +98 44 3101 0000 dr.saeedamir@yahoo.com Islamic Azad University Iran (Islamic Republic of) Age ≥ 18 years Septic shock according to Sepsis-3 definition Norepinephrine ≤ 0.2 mcg/kg/min or SOFA ≤ 7 Serum lactate ≥ 2 mmol/L Enrollment within 12 hours of shock diagnosis 18 years no limit Both Active major bleeding Platelet count < 30,000/µL Severe chronic liver failure (Child-Pugh C) End-stage malignancy (life expectancy < 3 months) Pregnancy Expected death within 24 hours Refusal of consent Chronic heart disease Chronic kidney failure Patients on long-term immunosuppressive therapy Patients with CAP(Community-acquired pneumonia) R65.21 Severe sepsis with septic shock Treatment - Devices N/A Intervention group: Patients randomized to the intervention group will receive standard sepsis care plus hemoperfusion with the HA380 cartridge (Jafron Biomedical, China). The intervention specifications are as follows:Timing of Initiation:Hemoperfusion will be initiated within 12 hours of septic shock diagnosis. Shock onset is defined as the time vasopressor infusion (norepinephrine) is started at ≥ 0.1 µg/kg/min in the presence of serum lactate ≥ 2 mmol/L and persistent hypotension despite adequate fluid resuscitation.Mode of Delivery:Hemoperfusion will be performed using a standalone hemoperfusion machine, not integrated into a CRRT circuit. This approach is chosen to enhance treatment consistency and avoid potential confounding from CRRT-related factors. If the patient has no indication for CRRT at enrollment, they will receive standalone hemoperfusion only.Technical Specifications:Cartridge: HA380Blood flow rate: 150–200 mL/minDuration per session: 4 hoursFrequency: Once daily for 3 consecutive days (total of 3 sessions)Vascular Access:A double-lumen central venous catheter (minimum 12 Fr) inserted into the femoral or internal jugular vein.Anticoagulation:Systemic unfractionated heparin according to the ICU standard protocol (target activated partial thromboplastin time: 1.5–2.0 times normal).CRRT After Hemoperfusion:After completion of the 3 HA380 hemoperfusion sessions, if the patient's condition deteriorates and clinical indications for CRRT develop (refractory oliguria, severe metabolic acidosis, refractory hyperkalemia, or fluid overload unresponsive to diuretics), the patient in the intervention group may receive CRRT at the discretion of the treating ICU physician. This decision will be documented in the medical record. Control group: The control group will receive standard septic shock management according to the Surviving Sepsis Campaign international guidelines. CRRT may be initiated at any time if clinically indicated, at the discretion of the treating physician. Change in Sequential Organ Failure Assessment (SOFA) Score from Baseline at Days 1, 3, and 7. Timepoint: Baseline (before intervention) and at Days 1, 3, and 7. Method of measurement: Sequential Organ Failure Assessment (SOFA) Score — the standard version recommended by the Sepsis-3 Task Force of the European Society of Intensive Care Medicine (ESICM). The tool grades dysfunction in 6 organ systems (respiratory, coagulation, hepatic, cardiovascular, neurological, renal) on a scale of 0 (normal) to 4 (severe failure). Total score ranges from 0 to 24. Originally developed by Vincent et al. (1996) and validated in numerous critical care studies. Change in Norepinephrine Dose (mcg/kg/min) from Baseline at 24, 48, and 72 Hours. Timepoint: Baseline (before intervention) and at 24, 48, and 72 Hours. Method of measurement: Norepinephrine infusion rate recorded from the syringe infusion pump via the electronic medical record or ICU monitoring chart, expressed as micrograms per kilogram of body weight per minute. Vasopressor-Free Days at Day 1, Day 3, and Day 7. Timepoint: Day 1, Day 3, and Day 7. Method of measurement: Number of complete calendar days (24-hour periods) during which the patient is alive and free from any vasopressor infusion (norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine), measured from enrollment to the end of the specified day. If the patient dies, the value is zero. Data are extracted from daily ICU monitoring charts. Capillary Refill Time (CRT) Baseline(before intervention) and at 24, 48, and 72 Hours. Timepoint: Baseline (before intervention) and at 24, 48, and 72 Hours. Method of measurement: Standardized capillary refill time measurement by applying firm pressure to the volar surface of the distal phalanx of the index finger for 5 seconds using a glass slide or examiner's finger, then releasing and measuring the time to return of normal color with a stopwatch in seconds. Room temperature is recorded at the time of measurement. A value of ≥ 3 seconds is considered abnormal. Vasoactive-Inotropic Score (VIS) Baseline(before intervention) and at 24, 48, and 72 Hours. Timepoint: Baseline (before intervention) and at 24, 48, and 72 Hours. Method of measurement: Vasoactive-Inotropic Score (VIS) calculated using the standard formula:VIS = dopamine dose + dobutamine dose + (100 × epinephrine dose) + (100 × norepinephrine dose) + (10,000 × vasopressin dose) + (10 × milrinone dose)All doses are expressed in mcg/kg/min (vasopressin in units/kg/min). Data are extracted from infusion pumps and ICU monitoring charts at the specified time points. Lactate Clearance at 24 Hours. Timepoint: Baseline (before intervention) and at hour 0(before intervention) and 24. Method of measurement: Serum lactate concentration measured from arterial or venous blood gas samples analyzed by the standard ICU blood gas analyzer. Lactate clearance at 24 hours is calculated as:Lactate clearance (%) = [(Baseline lactate − Lactate at 24 h) / Baseline lactate] × 100. PaO₂/FiO₂ Ratio at Baseline, 24, 48, and 72 Hours. Timepoint: Baseline (before intervention), 24, 48, and 72 Hours. Method of measurement: PaO₂/FiO₂ ratio calculated from arterial oxygen tension (PaO₂) measured by arterial blood gas analyzer and fraction of inspired oxygen (FiO₂) set on the ventilator or oxygen delivery device. Both values are recorded simultaneously from the ICU respiratory monitoring chart. Ratio is expressed in mmHg. 28-Day All-Cause Mortality. Timepoint: The first 28-Day of ICU admission. Method of measurement: Patient vital status at 28 days after enrollment, ascertained from hospital records, telephone follow-up with family members, or national vital registry. Death from any cause is recorded. ICU (intensive care unit) Length of Stay. Timepoint: Total day of ICU admission. Method of measurement: Number of complete calendar days spent in the ICU, from the date of ICU admission to the date of ICU discharge or death. If the patient dies in the ICU, length of stay equals the number of days from admission to death. Data extracted from the Hospital Information System (HIS). Ventilator-Free Days at Day 28. Timepoint: ICU (intensive care unit) Length of Stay. Method of measurement: Number of complete calendar days (24-hour periods) within the first 28 days after enrollment during which the patient is alive and free from invasive mechanical ventilation (endotracheal tube or tracheostomy). If the patient is extubated during a day and remains extubated until the end of that day (23:59), that day counts as a ventilator-free day. If the patient dies, the value is zero. Data extracted from ICU respiratory monitoring charts. Jafron Biomedical Co., LTD. Approved 2026-06-13 Research Ethics Committees, Research Ethics Committee of Islamic Azad University-Urmia Branch Salmas Road (start of the road) Urmia West Azarbaijan Iran (Islamic Republic of)