Pooled Human Plasma vs Crystalloid in The Management of Children Undergoing Instrumented Spinal Fusion for Scoliosis: A Double-Blind, Randomized Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 194
- 试验地点
- 2
- 主要终点
- Intraoperative blood loss
研究概览
简要总结
OCTAGON trial is a randomized, double-blinded, parallel-group non-inferiority multicenter (Helsinki and Turku University Hospitals, Finland) clinical trial according to CONSORT criteria.
194 adolescents with idiopathic (major curve > 45 degrees) or neuromuscular scoliosis (major curve > 50 degrees) are enrolled for the OCTAGON trial comparing pooled human plasma (Octaplas, 10mL/kg, active management) vs. Plasmalyte (10 mL/kg, placebo) before incision as part of the normal intraoperative fluid therapy. Data is collected at baseline and at each follow-up until a minimum of 2-year follow-up.
Outcomes Outcomes for the OCTAGON trial include 1) intraoperative blood loss (in mL, primary outcome) and the need for allogenic red blood cell infusion (percentage of patients). Secondary outcomes include health-related quality of life (Scoliosis Research Society 24 outcome questionnaire), postoperative pain (48-hour opioid consumption), operative time (hours), drain output (mL), hidden blood loss (mL), hospital stay, and complications (skin reactions, TRALI, deep surgical site infection, neurologic deficit).
Research questions and hypothesis Does prophylactic use of pooled human plasma decrease intraoperative blood loss in adolescents undergoing instrumented spinal fusion for scoliosis? We hypothesize that pooled human plasma will reduce intraoperative and total blood loss by 25% resulting in lower need for blood transfusion and fewer surgical site infections.
Objectives To compare the effect of pooled human plasma vs. crystalloid fluids on intraoperative bleeding and total blood loss (drain output and hidden blood loss) in children undergoing posterior spinal fusion for AIS and NMS. Adverse events will be recorded and reported as minor (skin reaction) or major (severe allergic reaction, transfusion related acute lung injury, TRALI, deep surgical site infection, neurologic injury).
Ethical aspects The PHP trial has been evaluated via European regulatory authority (EU CT: 2024-514857-31-00) and by Fimea (FIMEA/2024/006588). Informed consent is obtained from the parent(s). Results will be disseminated in high-quality peer-reviewed publications.
The individual patient safety and high-quality management of fractures and scoliosis is a priority in this trial. The randomization can be opened at any stage of the treatment process. Based on the clinical decision the randomized treatment can be terminated and treatment provided accord-ing to clinical decision making even if results will be evaluated using the intention to treat princi-ple. Pain management will be prioritized in every clinical scenario and parental presence is always possible.
详细描述
Introduction Total blood loss including intraoperative, drain output, and hidden blood loss equals to 40% of blood volume in patients undergoing posterior spinal fusion for paediatric spinal deformities. Despite the perioperative use of tranexamic acid and gelatine matrix with human thrombin, 14% of patients with adolescent idiopathic scoliosis (AIS) and 73% of patients with neuromuscular scoliosis (NMS) require allogenic red blood cell infusion (Soini et al. NASSJ 2022). Early use of pooled human plasma (PHP) may reduce total blood loss in these patients, but there are no studies in the paediatric population undergoing major surgery on this subject.
Objective To compare pooled human plasma (PHP, OCTAPLAS) vs. crystalloid (PLASMALYTE, comparator) for intraoperative bleeding, drain output, and hidden blood loss as well as the sum of these components (total blood loss) in children undergoing posterior spinal fusion for AIS. Adverse events will be recorded and reported as minor (skin reaction) or major (severe allergic reaction, transfusion related acute lung injury, TRALI; deep surgical site infection, neurologic injury). The investigators hypothesize that the use of PHP in the early perioperative management will reduce intraoperative blood loss (primary outcome), drain output, and hidden blood loss accounting for total blood loss and reduce the need for perioperative allogenic red blood cell infusion (secondary outcome) without increasing the risk for adverse events. Additionally, postoperative pain (opioid consumption and pain score, secondary outcome) may be decreased.
Outcomes Primary outcome is intraoperative blood loss (blood loss in mL after wound closure). Secondary outcomes include need for allogenic red blood cell infusion (percentage of patients at hospital release, health-related quality of life (Scoliosis Research Society 24 outcome questionnaire), postoperative pain (48-hour opioid consumption, pain visual analogue score), operative time (hours), drain output (mL), hidden blood loss (mL), hospital stay, and complications (skin reactions, TRALI, deep surgical site infection). Disease specific Scoliosis Research Society (SRS)-24 questionnaires are filled out preoperatively, at 6 months and 24 months during postoperative outpatient clinic visits.
Study design A randomized, double-blinded, multicenter (Helsinki and Turku University Hospitals, Finland) clinical trial according to CONSORT criteria.
After randomization, patients will be given in a blinded fashion (except for anaesthesia nurse) either 10 ml/kg (maximal dose 400 ml) pooled human plasma (OCTAPLAS or 10ml/kg (maximal dose 400 ml) crystalloid (PLASMALYTE) as an intravenous 1-hour infusion, as part of the standard anaesthesia of scoliosis surgery, starting at one hour before incision.
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
- 10 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent.
- •Aged between 10 and 21 years of age
- •Scoliosis requiring posterior scoliosis surgery using all pedicle screw technique for AIS (>45-degree major curve) or NMS (>50-degree major curve)
- •Normal whole spine MRI except for the spinal deformity (only for patients with adolescent idiopathic scoliosis as patients with neuromuscular scoliosis do not typically undergo MR images as they would need general anaesthesia)
排除标准
- •Immunoglobulin A-deficiency
- •Need for anteroposterior surgery
- •Need for three column vertebral resection
- •Diabetes mellitus
- •Abnormalities in blood coagulation (thromboplastin time below above or below of normal values, 70-130%)
- •Blood trombosytes less than 150 x E9/l
- •Body mass index over 40
- •Allergy or hypersensitivity to study medications or their ingredients
- •Pregnancy or breast-feeding, aim of becoming pregnant during the study.
- •Participation in another study and receipt of any other investigational agent during 2 year period of current investigation
- •Inability to provide written informed consent
- •Any significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk by participation in the study, or may influence the result of the study.
- •A history of drug or alcohol use that, in the opinion of the investigator, would interfere with adherence to study requirements.
- •Known history of, or documented positive hepatitis B or C or HIV infection Prior or concurrent malignancy
- •Aspartate transaminase (AST) or alanine transaminase (ALT) ≥ 3 x upper-limit of normal
- •Creatinine clearance (CrCl) < 60 ml/min measured by 24-hour urine collection or estimated from the Cockcroft and Gault formula
- •Clinically significant ECG findings as judged by the investigator
- •Amiodarone medication
- •Hyperkalemia
- •Renal insufficiency
- •Metabolic or respiratory alkalosis
- •Hypochlorhydria
- •Hypersensitivity for active component or additives.
研究组 & 干预措施
Pooled human plasma
Pooled human plasma (Octaplas, 10mL/kg, max 400 mL)
干预措施: Pooled human plasma (Drug)
Placebo
Crystalloid infusion (Plasmalyte, 10 mL/kg, max 400 mL)
干预措施: Placebo (Drug)
结局指标
主要结局
Intraoperative blood loss
时间窗: Exposure to closure
Bleeding during surgery (milliliters, mL). Typical intraoperative blood loss ranges 500 mL to 3000 mL representing 20% to 75% blood loss out of total blood volume. Higher blood loss during surgery is associated with worse outcomes.
次要结局
- Total blood loss(From exposure to drain removal at 24 hours postoperatively)
- Need for allogeneic blood transfusion(From surgical exposure to 72 hours postoperatively)
- Health-related quality of life(At 6 and 24 months)
- Adverse events(From surgery to 2-year follow-up)