Efficacy and Safety Study of CA330 Hemoadsorption Device on IL-6 Removal in Septic Patients

NCT03847961 | Unknown DMC

• 1 other identifier: 2018-030-02
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis persists to be the leading causes of morbidity and mortality worldwide. Moreover, the magnitude of health care resources utilized when managing septic patients is huge. All these hard facts call for constant efforts to optimize therapy. At present, the definitive therapy is adequate antibiotics and infectious source control. Fortunately, research has led to a better understanding of the pathophysiology of sepsis, in which the activation of multiple pro- and anti-inflammatory mediators plays a key role. This has led to the development of treatment strategies aimed at restoring a balanced immune response by eliminating/deactivating these inflammatory mediators. Whilst animal models of sepsis have provided encouraging results with strategies aiming at immune response modulation, clinical studies in patients using targeted pharmacological approaches have so far proved disappointing. Besides of acute kidney injury (AKI), renal replacement therapy (RRT) is applied to remove inflammatory mediators extracorporeally. Across the different modalities, the application of adsorption may help deactivate and decrease the peak elevation of these mediators in earlier course of sepsis, when levels of endotoxins and cytokines are extremely high. Recently, attempts to improve the outcome of sepsis patients with such devices, ie CytoSorb cytokine hemoadsorption and polymyxin B (Toraymyxin) endotoxin adsorption, have seen a certain renaissance. However, the clinical evidence to date supporting hemoadsorption for removal of endotoxins and/or proinflammatory mediators in sepsis remains incompetent and controversial. CA330 (Jafron Biomedical Co , Ltd, Zhuhai, China) is a hemoadsorption device containing hemocompatible, porous polymeric beads capable of removing cytokines and other mid-molecular weight toxins from blood by size exclusion and surface adsorption. Compared with HA330, improved resin synthesis technology makes CA330 a better performance in removing cytokines. This trial is the first to evaluate CA330 efficacy of cytokine reduction using the change in plasma interleukin (IL)-6 concentrations over time as a primary outcome. Although the trial was neither designed nor powered to evaluate outcome, we also evaluated organ function parameters as well as 28-day all-cause mortality.

Conditions

Sepsis

Keywords

sepsis; IL-6; hemoperfusion

Outcome Measures

Primary Outcomes (1)

• the reduction rate of IL-6 serum concentration at the initiation of first adsorption and at the end of the second adsorption

  (1-Concentration IL-6 end of second adsorption/ Concentration IL-6 initiation of first adsorption) ×100%

  from the initiation of first adsorption until the end of the second adsorption, assessed up to 24hours

Secondary Outcomes (13)

• the reduction rate of IL-10 serum concentration at the initiation of first adsorption and at the end of the second adsorption

  from the initiation of first adsorption until the end of the second adsorption, assessed up to 24hours

• the reduction rate of lactic acid serum concentration at the initiation of first adsorption and at the end of the second adsorption

  from the initiation of first adsorption until the end of the second adsorption, assessed up to 24hours

• the reduction rate of tumor necrosis factor-α (TNF-α) serum concentration at the initiation of first adsorption and at the end of the second adsorption

  from the initiation of first adsorption until the end of the second adsorption, assessed up to 24hours

• the dynamic change of Acute Physiology and Chronic Health Evaluation (APACHE II) score

  from Day0 to Day28

• ventilation time

  from Day0 to Day28

Other Outcomes (26)

• body temperature

  from Day0 to Day28

• heart rate

  from Day0 to Day28

• respiratory rate

  from Day0 to Day28

Study Arms (2)

Control Group

NO INTERVENTION

The control group receive routine treatment of sepsis only. All sites agree, when feasible, to follow the tenets of the Surviving Sepsis Campaign clinical practice guidelines for management of sepsis.

Experimental Group

EXPERIMENTAL

The experimental group receive routine treatment of sepsis combined with hemoperfusion with cytokine adsorption column (CA330).

Device: hemoperfusion with cytokine adsorption column (CA330)

Interventions

hemoperfusion with cytokine adsorption column (CA330) DEVICE

Hemoperfusion treatments are performed using a perfusion machine via centrally inserted standard dialysis catheters at a prescribed blood flow rate of 100-300ml/min. In the beginning, lower flow rate is recommended, if there is no discomfort, then gradually increases. Each patient received 2 hemoperfusion treatments within 24 hours with a target duration for each treatment of 120-180 minutes (minimum of 120 minutes). The shorter the interval between the two hemoperfusion is, the better. It is suggested that the second hemoperfusion be performed within 0-5 hours after the first one.

Experimental Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalized patients aged 18-75 years, regardless of gender;
• Meet the clinical criteria of sepsis according to the Third International Consensus Definitions for Sepsis;
• The diagnosis of sepsis is established within last 48 hours.
• Written informed consent is signed, and agreement to participate in all visits, examinations and treatments as required by the research program is achieved. If a patient is not able to give consent, the legal representative is asked to consent.

You may not qualify if:

• End-stage renal disease that need maintenance hemodialysis treatment;
• Congenital or acquired immunodeficiency disorders or those who had received organ transplantation within one year;
• Prescription of immunosuppressive medications (tripterygium wilfordii, mycophenolate mofetil, cyclophosphamide, FK506, etc.) or prednisolone for more than 10 mg/day (or the same dose of other hormone therapy) within 30 days;
• Coagulation dysfunction, severe bleeding tendency (prothrombin time, activated partial thromboplastin time prolonged significantly with bleeding, or fibrinogen less than 1.2 g/L with bleeding), active bleeding or uncontrolled acute massive bleeding within 24 hours;
• Malignant tumors, consumptive diseases, site of infection cannot be cleared (ie surgical patients who cannot be operated on) or body weight less than 35kg;
• A terminal state of organ failure (end stage of chronic obstructive pulmonary disease, pulmonary heart disease, heart dysfunction stage-IV, brain death or persistent vegetative state, chronic liver disease with hepatic encephalopathy, coagulation dysfunction, fluid retention and hepatocellular jaundice);
• Following results are detected during screening: platelet count \< 50 \*10\^9/L, neutrophil count \< 0.5 \*10\^9/L, hemoglobin \< 70 g/L;
• Despite of adequate volume resuscitation, vasopressors and hormones, the mean arterial blood cannot maintain above 65 mmHg;
• Those who have been participating in or participated in another interventional clinical study within 30 days prior to enrollment, such as the clinical study of related drugs or medical devices affecting immunity (ie Xuebijing, ulinastatin, continuous renal replacement therapy, etc.);
• Anaphylaxis to materials of cardiopulmonary bypass, anticoagulants and hemoperfusion or other serious allergic history;
• Those who are not suitable for this clinical trial, which is determined by researchers, such as pregnant or lactating women, current drug addicts, patients with severe mental or neurological disorders, and those who have a history of alcohol abuse and cannot be terminated.

Sponsors & Collaborators

• First Affiliated Hospital, Sun Yat-Sen University: lead
• Sixth Affiliated Hospital, Sun Yat-sen University: collaborator
• Guangzhou First People's Hospital: collaborator
• Zhujiang Hospital: collaborator
• Beijing Chao Yang Hospital: collaborator
• Peking University Shenzhen Hospital: collaborator
• Fujian Provincial Hospital: collaborator
• Wuhan University: collaborator

Study Sites (1)

the First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

RECRUITING

MeSH Terms

Conditions

Sepsis

Interventions

Hemoperfusion

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Xiangdong Guan, PhD

  First Affiliated Hospital, Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zimeng Liu, PhD

CONTACT

+8618925002766; sumslzm@163.com

Yao Nie, PhD

CONTACT

+8618826471751; nieyao850622@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of the Department of Critical Care Medicine, Chairman of the Chinese Society of Critical Care Medicine

Model Details: Eligible patients are stratified by site and randomly assigned in a 1:1 ratio to either CA330 hemoperfusion plus conventional medical therapy group or conventional medical therapy group.

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: February 20, 2019
• Study Start: December 17, 2018
• Primary Completion: February 1, 2020
• Study Completion: October 1, 2020
• Last Updated: February 22, 2019

Record last verified: 2019-02

Locations

CN (1)