Intravenous DNase I for the Treatment of Sepsis: A Phase I Safety and Feasibility Study in ICU Patients
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Number of patients recruited per month from the start of the study
研究概览
简要总结
Phase I dose-escalation safety and feasibility of IV DNase I in ICU septic patients.
详细描述
In sepsis, the release of 'neutrophil extracellular traps' (NETs) by activated neutrophils may contribute to organ damage by acting as scaffolds that trap blood cells and fibrin clots. Excessive NET formation can occlude the vasculature, promoting thrombosis and tissue hypoperfusion. This is a trial on a novel IV therapy for septic patients that shows promise in multiple animal models of sepsis. The therapy, DNase I, is an enzyme that helps to dismantle NETs by digesting cell-free DNA (cfDNA), the major structural component of NETs. The objective of this study is to conduct a Phase I dose-escalation safety and feasibility of IV DNase I in ICU septic patients. The results of this study may justify a future Phase II trial of the efficacy and safety of DNase I for critically ill patients with sepsis.
This trial proposes
- - To determine the safety, feasibility and maximum tolerated dose (MTD) of using DNase I in septic patients
- - To evaluate clinical endpoints common in the critically ill such as organ dysfunction severity and trajectory, ICU length of stay, and mortality.
- - To describe the effects of DNase I on blood coagulation and NETs release
- - To collect samples for future studies on coagulation and immune function in sepsis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age of ≥18 years
- •Admitted to the ICU in the last 48 hours
- •Suspected or proven infection as the admitting diagnosis
- •A sequential (sepsis) organ function assessment (SOFA) score of ≥2 above baseline
- •Expected to remain in the ICU for ≥ 72 hours
排除标准
- •No consent/inability to obtain consent from a substitute decision-maker
- •Have other forms of clinically apparent shock, including cardiogenic, obstructive (massive pulmonary embolism, cardiac tamponade, tension pneumothorax), hemorrhagic, neurogenic, or anaphylactic shock
- •Have a significant risk of bleeding as evidenced by one of the following:
- •Surgery requiring general or spinal anesthesia within 24 hours before enrolment
- •The potential need for surgery in the next 24 hours
- •Evidence of active bleeding
- •A history of severe head trauma requiring hospitalization
- •Intracranial surgery, or stroke within three months before the study
- •Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or mass lesions of the central nervous system
- •A history of congenital bleeding diatheses
- •Gastrointestinal bleeding within five weeks before the study unless corrective surgery had been performed
- •Trauma is considered to increase the risk of bleeding
- •Presence of an epidural catheter
- •Need for therapeutic anticoagulation
- •Receiving DNase I by inhalation
- •Terminal illness with a life expectancy of fewer than three months
- •Pregnant and/or breastfeeding
研究组 & 干预措施
Intravenous DNase I
We will enroll up to 36 Participants; each is receiving repeated unit doses of DNase I, BID, delivered by IV infusion over 3 or 7 consecutive days (12 +/- 1 hour apart) according to the following dose-escalation schedule with up to 6 Participants per dose panel.
- Panel 1: 25 µg/kg, BID for 3 days (cumulative dose: 150 µg/kg)
- Panel 2: 25 µg/kg, BID for 7 days (cumulative dose: 350 µg/kg)
- Panel 3: 125 µg/kg, BID for 3 days (cumulative dose: 750 µg/kg)
- Panel 4: 125 µg/kg, BID for 7 days (cumulative dose: 1750 µg/kg)
干预措施: Intravenous DNase I (Drug)
Control
We will also enroll 12 septic Participants who do not receive intravenous DNase I (as Comparator Group). These patients will be recruited contemporaneously based on the same inclusion and exclusion criteria.
结局指标
主要结局
Number of patients recruited per month from the start of the study
时间窗: up to 24 months
Number of patients recruited per month
Number of patients who completed the protocol
时间窗: up to 7 days
The ability to complete study infusion and blood collection as prescribed
次要结局
- Time to Hospital discharge(up to 90 days)
- European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score(At day 90)
- Collection of Research Biomarkers related to inflammation and coagulation(up to day 14)
- Duration of ICU admission(up to 9 months)
- Sequential Organ Failure Assessment (SOFA) score(Baseline to Day 10)
- Organ support free days(at Day 28)
- Mortality at Day 90(up to day 90)