Safety and Efficacy of Low-dose Prostacyclin Administration and Blood Pressure Target in Addition to Standard Therapy, as Compared to Standard Therapy Alone, in Post-cardiac-arrest-syndrome Patients - a Randomized, Controlled, Double-blinded Investigator-initiated Trial.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Mean change i plasma biomarkers reflecting endothelial activation and damage
研究概览
简要总结
Objective: Safety and efficacy of low-dose prostacyclin administration and blood pressure target in addition to standard therapy, as compared to standard therapy alone, in post-cardiac-arrest-syndrome (PCAS) patients.
详细描述
Trial Rationale: Therapeutic interventions directed towards the damaged endothelium may improve outcome for patients with PCAS. Prostacyclin/Iloprost (PGI2) is an endogenous prostanoid which is formed and released by endothelial cells with anti-platelet, vasodilatory and cytoprotective properties36 and is expected to be beneficial by protecting and deactivating the endothelium and by restoring vascular integrity in patients suffering from endothelial breakdown.
Trial Population: Participants in the trial must be adult patients (≥18 years of age) with out-of-hospital cardiac arrest (OHCA) of presumed cardiac cause admitted to the Dept. of Cardiology, 2143, Rigshospitalet, Copenhagen.
Trial Design: Randomized, placebo controlled, double-blind investigator-initiated trial in 40 OHCA patients. 48 hours of active study drug (Iloprost, 1 ng/kg/min) versus placebo (saline) infusion.
Patients in both randomization groups will be treated in accordance with state-of-the art therapy including targeted temperature management. Interventions are considered emergency procedures and study drug infusion should be commenced as soon as possible after sustained return of spontaneous circulation (ROSC), screening and randomization.
Patients will only be enrolled after informed consent, but as the treatment has to be initiated earliest possible after the out of hospital cardiac arrest diagnosis i.e., at a time-point where patients are temporarily incompetent, scientific guardians will co-sign the informed consent form before inclusion. Next-of-kin and the patients' general practitioner will co-sign as soon as possible and the patient will provide informed consent whenever 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
- 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
- •Age ≥18 years
- •OHCA of presumed cardiac cause
- •Sustained ROSC*
- •Unconsciousness (GCS <8) (patients not able to obey verbal commands) after sustained ROSC*
- •Target temperature management is indicated.
排除标准
- •Conscious patients (obeying verbal commands)
- •Females of childbearing potential (unless a negative human chorionic gonadotropin (HCG) test can rule out pregnancy within the inclusion window)
- •Patients weighing more than 135kg
- •In-hospital cardiac arrest (IHCA)
- •OHCA of presumed non-cardiac cause, e.g. after trauma or dissection/rupture of major artery OR Cardiac arrest caused by initial hypoxia (i.e. drowning, suffocation, hanging).
- •Known congenital bleeding diathesis (medically induced coagulopathy due to treatment with Vitamin K antagonists, Thrombininhibitors, Factor Xa inihbitors, ADP-receptor inhibitors, Aspirin, Asasantin, Persantin, NSAID, unfractionated and low molecular weight heparin does NOT exclude the patient).
- •Suspected or confirmed acute intracranial bleeding
- •Suspected or confirmed acute stroke
- •Unwitnessed asystole
- •Known limitations in therapy and Do Not Resuscitate-order
- •Known disease making 180 days survival unlikely
- •Known pre-arrest CPC 3 or 4
- •>4 hours (240 minutes) from ROSC to screening
- •Systolic blood pressure <80 mm Hg in spite of fluid loading/vasopressor and/or inotropic medication/intra-aortic balloon pump/axial flow device*
- •Temperature on admission <30°C.
- •Known allergy to Prostacyclin analogues
研究组 & 干预措施
Iloprost + M1006B offset by -10 mmHg
Administration of 1 ng/kg/min Ilomedin® as a 48h continuous i.v infusion. Administration of blood pressure modules M1006B: offset by -10 mmHg
Intervention: Drug: Iloprost + M1006B offset -10mmHg
干预措施: Iloprost (Drug)
Iloprost + M1006B offset by -10 mmHg
Administration of 1 ng/kg/min Ilomedin® as a 48h continuous i.v infusion. Administration of blood pressure modules M1006B: offset by -10 mmHg
Intervention: Drug: Iloprost + M1006B offset -10mmHg
干预措施: Phillips M1006B, offset by -10mmHg (Device)
Iloprost + M1006B, No offset
Administration of 1 ng/kg/min Ilomedin® as a 48h continuous i.v infusion Administration of blood pressure modules M1006B: No offset
Intervention: Drug: Iloprost + M1006B, No offset
干预措施: Iloprost (Drug)
Iloprost + M1006B, No offset
Administration of 1 ng/kg/min Ilomedin® as a 48h continuous i.v infusion Administration of blood pressure modules M1006B: No offset
Intervention: Drug: Iloprost + M1006B, No offset
干预措施: Philips M1006B, No offset (Device)
Placebo + M1006B offset by -10 mmHg
Double dummy 0.9% saline as a 48h continuous i.v infusion. Administration of blood pressure modules M1006B: offset by -10 mmHg
Intervention: Drug: Placebo + M1006B offset -10mmHg
干预措施: Saline (Drug)
Placebo + M1006B offset by -10 mmHg
Double dummy 0.9% saline as a 48h continuous i.v infusion. Administration of blood pressure modules M1006B: offset by -10 mmHg
Intervention: Drug: Placebo + M1006B offset -10mmHg
干预措施: Phillips M1006B, offset by -10mmHg (Device)
Placebo + M1006B, No offset
Double dummy 0.9% saline as a 48h continuous i.v infusion Administration of blood pressure modules M1006B: No offset
Intervention: Drug: Placebo + M1006B, No offset
干预措施: Saline (Drug)
Placebo + M1006B, No offset
Double dummy 0.9% saline as a 48h continuous i.v infusion Administration of blood pressure modules M1006B: No offset
Intervention: Drug: Placebo + M1006B, No offset
干预措施: Philips M1006B, No offset (Device)
结局指标
主要结局
Mean change i plasma biomarkers reflecting endothelial activation and damage
时间窗: 48 hours
Mean change in biomarkers indicative of endothelial activation and damage (sE-selectin, syndecan-1, soluble thrombomodulin (sTM), soluble vascular endothelial growth factor (sVEGF), nucleosomes) and sympathoadrenal overactivation (epinephrine/norepinephrine) from baseline to 48 hours post-randomization.
次要结局
- Feasibility of blood pressure target intervention.(48 hours)
- Mean change in hemostatic profile evaluated by TEG, Multiplate, Flowcytometry(48 hours)
- Blood pressure target influence on primary outcomes measured by mean change in plasma biomarkers.(48 hours)
研究者
Pär Johansson
MD, DMSc, MPA
Rigshospitalet, Denmark
