Effects on Sublingual Microcirculation of IgGAM Immunoglobulins (Pentaglobin®) in Severe Septic/Septic Shock Patients: a Randomized Controller Trial.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Perfused vessel density (PVD)
研究概览
简要总结
IgM-enriched immunoglobulins (IgGAM; Pentaglobin ® ) are new therapy for sepsis and septic shock since they support immune system especially in case of " immunoparalysis" . However IgGAM isn't commonly prescribed, few centres use it as routine in severe infections and there aren't any guidelines to determine how and when to use them.
Microcirculatory dysfunction is a crucial aspect in the pathogenesis of sepsis-induced organ dysfunction, resulting in hypoperfusion and tissue hypoxia. Unpublished clinical data suggest a beneficial effect of IgGAM at microvascular level proved with near infrared spectroscopy and Vascular occlusion test (VOT).
This study is a double blind phase II prospective randomised controlled trial that will include patients admitted to the Intensive Care Unit of the University Hospital "Ospedali Riuniti" of Ancona, after no more than 24 hours from development of severe sepsis or septic shoc.
Patients will be randomized into two groups (treaties and controls): patients in group of the treaties will be submitted to infusion of IgGAM conjugate (Pentaglobin ®) at dosage of 250 mg/kg IV (5 mL/kg) per day (rate of 0.4 mL/kg/h), for 72 hours. The controls will receive equal amount of physiological NaCl solution (0.9%) as placebo. Neither the patient nor the staff nurses and MD will be aware of the group and of the treatment applied. IgGAM solutions or NaCl 0.9% will be provided by the hospital pharmacy in similar bags. The remaining treatments will not be changed in any way and will be at the discretion of the doctor who's in charge of the patient. All patients of the two groups will receive the optimal therapy for their conditions, according to good medical clinical practice (GMP), with appropriate antibiotic therapy, vasoactive and infusional therapy
详细描述
Sepsis is a complex set of signs and symptoms caused by Systemic Inflammatory Response Syndrome (SIRS) to an infection. Sepsis-related mortality is directly proportional to the severity of organ dysfunction, and can be up to 80% in the case of septic shock.
Due to the pro-inflammatory response to this insult, tissues can be damaged far away from the primary site of infection. Concurrently with pro-inflammatory cytokines, the immune system produces anti-inflammatory mediators such as IL-10, which exert a compensatory antagonist response. The imbalance toward the anti-inflammatory one can conduce to "immuno-paralysis" that undermines the defense of the organism against infection.
Antibodies play a crucial role in fighting infections; low levels of protective antibodies are directly related to worst outcome. In consideration to that, polyvalent immunoglobulins (Ig) represent a potential therapeutic support for modulation of immune response and of inflammation in sepsis and septic shock.
They contain a broad spectrum of antibodies direct against a wide variety of bacterial antigens (all three classes normally found in human plasma - IgG and IgM and IgGAM conjugate).
In addition to antibody activity and antigen neutralization, benefits of Ig may include: inactivation of bacterial toxins (endotoxin and exotoxins); increased clearance of lipopolysaccharide; stimulation of leukocytes and their bactericidal activity through mechanism of opsonization; reduction in the activity of the classical pathway of the complement; modulation of cytokine production by blood mononuclear cells; synergistic activity with antibiotics.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •severe sepsis
- •septic shock
排除标准
- •pregnant women
- •severe sepsis/septic shock for more than 24 hours
- •chronic renal failure
- •terminal state with a life expectancy of less than 24 hours
- •contraindications to treatment with IgGAM
- •lack of informed consent will be excluded.
研究组 & 干预措施
Pentaglobin®
Patients will receive Immunoglobulins IgGAM (Pentaglobin®) at dosage of 250 mg/kg IV (5 mL/kg) per day (rate of 0.4 mL/kg/h), for 72 hours. Microcirculation will be monitored with sublingual microcirculation device (Cytocam®) and Near InfraRed Specrotcopy (NIRS, Hutchinson®).
干预措施: Pentaglobin® (Drug)
Physiologic Solution
Patients will receive physiologic solution (NaCl 0.9%) at a dosage of 5 ml/Kg per day for 72 hours. Microcirculation will be monitored with sublingual microcirculation device (Cytocam®) and Near InfraRed Specrotcopy (NIRS, Hutchinson®)
干预措施: Physiologic solution (Drug)
结局指标
主要结局
Perfused vessel density (PVD)
时间窗: 72 hours
The perfused vessel density (PVD), unity of measure mm/mm2, is detected in vivo by Incident Dark Field Imaging at sublingual microcirculation. It represents the quantity of well perfused vessels at microcirculatory level.
次要结局
- StO2 upload(72 hours)
- Microcirculatory Flow Index (MFI)(72 hours)
- Arterial blood lactate(72 hours)
- SOFA score (Sequential Organ Failure Assessment)(72 hours)
研究者
Abele Donati, MD
Associate Professor of Anesthesiology
Università Politecnica delle Marche