Efficacy and Safety of 72-hour Infusion of Prostacyclin (1 Nanogram(ng)/Kilo(kg)/Minute(Min)) in Patients With Septic Shock Induced Endotheliopathy - a Multicentre Randomized, Placebo-controlled, Blinded, Investigator-initiated Trial"
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 279
- 试验地点
- 6
- 主要终点
- Modified Sequential Organ Failure Assessment (SOFA)
研究概览
简要总结
The purpose of this trial is to investigate the efficacy and safety of continuous intravenous administration of low dose iloprost versus placebo for 72-hours, in up to a total of 380 patients with septic shock suffering from organ failure.
The study hypothesis is that iloprost may be beneficial as an endothelial rescue treatment as it is anticipated to deactivate the endothelium and restore vascular integrity in septic shock patients suffering from organ failure caused by endothelial breakdown, ultimately improving survival.
详细描述
Patients with the most severe type of sepsis, those with septic shock have a mortality rate between 30% to 45% due to multiple organ failure. The poor outcome of shocked patients, and especially those with sepsis, may by related to microvascular endothelial dysfunction. Evidence support that iloprost infusion significantly improved endothelial function and integrity,
The main objective in this trial is to investigate whether continuous infusion of lov dose iloprost at a dose of 1 ng/kg/min for 72-hours is safe and significantly reduce organ failure score in the intensive care unit (ICU) compared to infusion of placebo in patients with septic shock induced endotheliopathy (SHINE).
Patients that are eligible for this trial will be temporarily incompetent due to acute severe illness relating to septic shock, therefore informed consent will be obtained from a scientific guardian. Next-of kin and subsequently the patient will co-sign as soon as possible hereafter. During the trial, patient will be give continuous infusion of low dose iloprost or placebo for 72 hours as well as additional blood samples will be obtained daily for the first 72 hours. Follow up on organ failure, mortality and quality of life will be performed on dag 28 and 90.
This trial is conducted in accordance with the Helsinki 2 Declaration and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Guideline for Good Clinical Practice (ICH-GCP) and in compliance with the protocol. As part of the quality assurance on-site monitoring visit will be performed by the an independent GCP-unit including source data verification. Standard Operation Procedure (SOP) to address protocol specific procedures such as data collection and adverse event reporting are developed.
The number of patients participating is based on a power calculation using the data on mean daily SOFA score from a recent randomized, double blind, placebo controlled clinical trial in patients with septic shock: Levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARD). If the true effect of the intervention is a reduction in mean daily SOFA score of 20% (relative) and providing the trial with 90% power to detect this difference at a significance level of 0.05 will require a sample size of 380 patients.
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)
盲法说明
Patient, investigator, outcome assessor and care provider will be blinded.
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
- •All the following criteria must be fulfilled:
- •Adult intensive care patients (age ≥ 18 years)
- •Septic shock defined according to the Sepsis-3 criteria:
- •suspected or documented infection
- •persisting hypotension requiring vasopressors to maintain a mean arterial blood pressure of 65 mmHg or above
- •Lactate level of 2 mmol/L or above despite fluid therapy within the last 3 hours at screening
- •Soluble thrombomodulin (sTM) above 10 ng/mL
排除标准
- •Patients who fulfil any of the following criteria will be excluded:
- •Withdrawal from active therapy
- •Known hypersensitivity to iloprost.
- •Life-threatening bleeding as defined by the treating physician
- •Known severe heart failure (New York Heart Association (NYHA) class IV)
- •Suspected acute coronary syndrome
- •Previously included in this trial
- •Septic shock for more than 12 hours at the time of screening
- •Informed consent cannot be obtained
- •Included in other clinical trials with prostacyclin within 90 days
研究组 & 干预措施
Iloprost
Patients randomized to active treatment (n=190 patients) will receive continuous infusion of iloprost for 72 hours after inclusion or until discharge to ward or death, whichever comes first.
干预措施: Iloprost (Drug)
Placebo
Patients randomized to placebo treatment (n=190 patients) will receive continuous infusion of placebo for 72 hours after inclusion or until discharge to ward or death, whichever comes first.
干预措施: Isotonic saline (Drug)
结局指标
主要结局
Modified Sequential Organ Failure Assessment (SOFA)
时间窗: Up to 90 days after randomization
Mean daily modified SOFA score in the intensive care unit (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; range score 0-20).
次要结局
- Mechanical ventilation free days(Until ICU discharge, maximun 90 days after randomization)
- Renal replacement free days(Until ICU discharge, maximun 90 days after randomization)
- 28 and 90-day mortality(Day 28 and 90 after randomization)
- Vasopressor free days(Until ICU discharge, maximun 90 days after randomization)
- Serious adverse reactions (SARs)(Until day 7 after randomization)
- Serious adverse events (SAEs)(Until day 7 after randomization)
研究者
Jakob Stensballe, MD, PhD
Sponsor
Rigshospitalet, Denmark