Influence of Argipressin on Blood Loss During Hepatic Resection; a Double-blinded, Randomized Placebo-controlled Trial (ARG-01)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 248
- 试验地点
- 1
- 主要终点
- Blood loss
研究概览
简要总结
Infusion of Argipressin during hepatic resection surgery may reduce blood loss. It may also reduce transfusion requirements, and mitigate the perioperative inflammatory response compared to placebo. Subjects will be randomized to infusion of Argipressin or placebo during surgery. Blood loss, transfusion requirements, surgical data including length of stay in hsopital, inflammatory markers and markers of renal- intestinal- and cardiac injury will be assessed. Two sub-studies has been added; one for evaluation of coagulation function, and one for assessment of pain scores and morphine consumption.
详细描述
Hepatic resection is a major surgical intervention with high risk of substantial blood loss. The surgical means to reduce blood loss may impair perfusion and induce intestinal congestion. If blood flow to the liver can be influenced by pharmacological means, blood loss and transfusion requirements may be reduced. Moreover, the inflammatory system is involved in cancer development, and the anti-inflammatory properties of Argipressin may decrease the inflammatory response after hepatic surgery.
Argipressin is an endogenous substance, and part of the body's response to stress and trauma. Argipressin affects V1-receptors to produce vasoconstriction. It is also involved in inflammatory reactions and affects platelets.
Patients will be stratified according to planned type of surgery (open/laparoscopic) and planned extent of resection, and randomized to etiher infusion of Argipressin or placebo (normal saline) during surgery. In all other aspects, the participants will be treated according to the institution protocol for hepatic resection. The study drug will be started as soon as the central line is placed, and discontinued at the end of surgery. Hemodynamic data will be collected during surgery, and blood and urine-samples will be obtained during and after surgery for analysis of inflammatory markers and markers of organ injury.
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
Randomisation will be handled by a nurse not involved in the study, and both the patient, treating physician and nurse, the study nurse and the investigators will be blinded to the study treatment.
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
- •Participant planned for hepatic resection (open or laparoscopic, regardless of indication for surgery).
- •Age ≥18 years.
- •ASA class I-III.
- •Signed informed consent form
排除标准
- •Participant does not understand the given information, and/ or cannot give written informed consent.
- •Simultaneous operation of tumor with other localization, or surgery for superficial single hepatic tumor less than 2 cm, expected to be of short duration and with minimal blood loss.
- •Terminal kidney failure (estimated preoperative GFR< 15 ml/min)
- •Pregnancy or lactation.
- •Known allergy to Empressin®.
- •Patient included in other interventional study, interacting with the endpoints in the present study, or previous randomization in this study.
- •Hyponatremia (S-Na < 130 mmol/L)
- •Patient considered ineligible for other surgical or medical reason.
- •Present infection. Patients with systemic inflammatory disease, inflammatory bowel disease or preoperative corticosteroid treatment will not be eligible for the subgroups where cytokines and interleukins are investigated.
研究组 & 干预措施
Argipressin
Patients will be treated with Empressin® 0.8 U/ml, 0.056 ml/kg/h during surgery.
干预措施: Argipressin (Drug)
Placebo
Patients will receive normal saline 0.056 ml/kg/h during surgery.
干预措施: Placebo (Drug)
结局指标
主要结局
Blood loss
时间窗: through surgery, an average of 8 hours
Blood loss at the end of surgery, measured according to the investigator's instructions, by visual assessment of suction devises and gauze, and subtraction of ascites and irrigation fluids.
次要结局
- Blood transfusion(At end of surgery and until postoperative day 2 or 5 respectively)
- Inflammatory markers-regular(Measured throughout the study until postoperative day 2 (laparoscopic resection) or postoperative day 5 (open resection))
- I-FABP (change in organ damage markers)(from baseline to postoperative day 1)
- surgical data(at the end of surgery, approximately 5 hours after start of surgery)
- Noradrenaline use (anesthesiologigal data)(during surgery)
- use of diuretics(until postoperative day 1)
- Inflammatory markers- extended(Measured at throughout the study until postoperative day 2.)
- Lactate (change in organ damage markers)(from baseline to postoperative day 1)
- CVP (anesthesiological data)(during surgery)
- urine output(until postoperative day 1)
- Length of stay(From admission in hospital to discharge, expected time 2-5 days but will be followed until actual discharge, which may be several months.)
- Cardiac marker (change in organ damage markers)(from baseline to postoperative day 1)
- Tranexamic Acid(at the end of surgery, approximately 5 hours after start of surgery)
- postoperative complications(30 days after surgery)
- Plasma Creatinine (change in organ damage markers)(from baseline (before surgery) to postoperative day 2 and 5 respectively.)
- Urine samples (change in organ damage markers)(from baseline to end of surgery, approximately 5 hours)
研究者
Kristina Svennerholm
Principal investigator, MD, PhD
Sahlgrenska University Hospital