Blood Purification for the Treatment of Critically Ill Patients With Pathogen Associated Shock: A Multicenter, Randomized Controlled Feasibility Trial
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 18
- 主要终点
- Efficacy - ICU-free days in the first 28 days
研究概览
简要总结
This study is a multi-center, randomized controlled feasibility trial to evaluate the initial safety and efficacy of a novel extracorporeal blood purification (EBP) therapy in critically ill patients with pathogen associated shock across 15 U.S. sites. Adults (18 years old and older) admitted to the ICU with all of the following:
• Pathogen associated shock defined as:
- The need for vasopressors to maintain mean arterial pressure (MAP) ≥ 65 mmHg despite adequate fluid resuscitation
- Presence of a pathogen detected in the bloodstream within 72 hours of screening using commercially available in-vitro diagnostic testing
详细描述
Patients meeting the eligibility criteria will be randomized to receive either treatment with the investigational device (Seraph 100) + 'State of the Art' care versus 'State of the Art' care alone. This study is a multi-center, un-blinded, randomized controlled feasibility trial to evaluate the initial safety and efficacy of Seraph 100 in critically ill patients with pathogen associated shock across 15 US sites. This study will not be done in a blinded fashion from either the patient or caregiver perspective given: 1) the need for invasive, central line placement, and 2) to ensure that limited hospital resources (e.g., hemodialysis machines) are available for patients that require therapy. While the study trial will not be conducted in a blinded fashion, the members of the study team that do the data analysis will be blinded.
The target population is adults (18 years old and older) admitted to the ICU with all of the following:
- Pathogen associated shock AND
- The need for vasopressors at any dose to maintain mean arterial pressure (MAP) ≥ 65 mm Hg despite adequate fluid resuscitation.
Study Arms: Patients will be randomized to receive either Arm 1: Seraph 100 treatment plus 'State of the Art' or Arm 2: 'State of the Art' care alone. "State of the Art care" will be defined as the treatment algorithms outlined in the Surviving Sepsis Campaign for the treatment of septic shock, available at https://www.sccm.org/SurvivingSepsisCampaign/Home.
Study Randomization and stratification: Patients who qualify will be immediately randomized. The study will randomize patients 2:1 to investigational product plus 'State of the Art' care and 'State of the Art' alone, respectively. Upon randomization, patients will be stratified by age (≥65 and <65). While ideally, the research team would stratify by other variables (to include demographics, causative pathogen, GCS, SOFA, associated organ failure, and pre-existing conditions), given the small number of patients in this trial (particularly in the control group) this is not possible.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Unblinded
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Admitted to an ICU with pathogen associated shock defined as:
- •The need for vasopressors to maintain mean arterial pressure (MAP) ≥ 65 mmHg despite adequate fluid resuscitation, AND
- •Presence of a pathogen detected in the bloodstream within 72 hours of screening using commercially available in-vitro diagnostic testing
- •Male or non-pregnant female adult
- •At least 18 years of age at time of enrollment
排除标准
- •Pregnant or breast feeding
- •Anticipated transfer to another hospital (that is not a study site) within 72 hours for any reason
- •Not anticipated to survive more than 24 hours
- •Known allergy to heparin sodium
- •Patients who cannot tolerate placement of double-lumen catheter
- •High risk of bleeding (platelet count <50mm3 or International Normalized Ratio (INR) >2) unless adequate line for treatment already placed (e.g. ECMO or RRT/CRRT)
- •Inability to tolerate extracorporeal therapy (defined as MAP<65 despite fluids and vasopressors)
- •Advanced cancer (defined as stage IV) with life expectancy of less than 30 days
- •Unable to obtain informed consent from either patient or legally authorized representative (LAR)
- •Hypotension and volume depletion due to etiologies other than sepsis.
- •Neutropenia with an absolute neutrophil count <500mm3
- •Patients must be treated with one of the antimicrobial agents listed in the Antimicrobial Management Guideline (Table 19). Patients who require treatment with an antimicrobial outside of this list while still receiving treatment with the investigational device must be excluded from the study.
- •If a patient enters the study and later requires a change in the antimicrobial agent used to one which is not listed in the Antimicrobial Management Guideline while still receiving treatment with the investigational device, that patient must be removed from this trial. Clinical data for any patient removed from the trial for this reason will continue to be collected for safety evaluation".
- •Patient is a prisoner or member of a different vulnerable population that should not be included in the study per the investigator or IRB/ethics committee.
- •Advanced directive for "Do Not Resuscitate".
研究组 & 干预措施
1- Seraph-100 plus State of the Art Care
The Seraph 100 Filter is a single use, disposable column packed with ultra-high molecular weight polyethylene beads which have been modified to contain endpoint attached heparin on the surface. Seraph 100 is an extracorporeal broad-spectrum sorbent hemoperfusion device for reduction of pathogens from the bloodstream. It is intended for use with standard, commercially available bloodlines compatible with the pump system used. Female Luer connectors are required to connect to the Seraph 100 blood ports.
干预措施: Seraph-100 + State of the Art Care (Device)
2 - State of the Art Care
"State of the Art care"is defined as the treatment algorithms outlined in the Surviving Sepsis Campaign for the treatment of septic shock, available at https://www.sccm.org/SurvivingSepsisCampaign/Home
干预措施: State of the Art Care (Device)
结局指标
主要结局
Efficacy - ICU-free days in the first 28 days
时间窗: First 28 days
Alive and not in the ICU (for at least a fulle 24 hours) in the first 28 days from the time of randomization
Safety - Adverse Events
时间窗: Discharge from hospital
SAEs and \>/= grade 3 AEs per CTCAE v5 evaluated from enrollment until the end of hospitalization
次要结局
- Kidney replacement therapy-free days in the first 28 days(First 28 days)
- Ventilator-free days in the first 28 days(First 28 days)
- Mortality(28 days)
- Vasopressor-free days in the first 28 days(First 28 days)
- Hospital Stay(through study completion, an average of 90 days)
- Survival(through study completion, an average of 90 days)