Postoperative Continuous Intravenous Tranexamic Acid Infusion to Reduce Blood Loss in Non-Ambulatory Children With Cerebral Palsy Following Bilateral Bony Hip Reconstructive Surgery: A Phase III Parallel-Group Randomised Placebo-Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Mean change between treatment arms in postoperative haemoglobin mass loss, measured on postoperative day 5 or day of discharge (whichever is earlier) and estimated using the HAEmoglobin Mass loss DuRing the periOperative Period (HAEMDROP) formula
研究概览
简要总结
TABLO (Tranexamic Acid to reduce Blood Loss after varus derotation Osteotomy) is a clinical trial of postoperative tranexamic acid vs placebo in non-ambulatory children with cerebral palsy (CP) undergoing reconstructive hip surgery.
Improving surgical outcomes is a high priority in this patient population given the high risk of bleeding and the diminished capacity for these children to withstand substantial blood loss. Preliminary data from the study institution indicates that approximately one third of these patients receive transfusion of blood products in the postoperative period. There is growing evidence that hidden blood loss occurring in the postoperative period is substantial and can potentially be attenuated with the administration of Tranexamic Acid (TXA). However, trials on postoperative TXA have been carried out exclusively in adult surgical populations.
详细描述
TABLO (Tranexamic Acid to reduce Blood Loss after varus derotation Osteotomy) is a parallel-group randomised placebo-controlled trial of postoperative tranexamic acid vs placebo in children with CP undergoing bilateral varus derotational osteotomy (VDRO) surgery. The allocation ratio is 1:1 (placebo: intervention), and the trial will be powered to detect a difference in postoperative blood loss calculated using a haemoglobin mass loss formula. Improving perioperative outcomes is a high priority in this patient population given the high risk of bleeding from this surgical intervention and the reduced physiological reserve in these children. Preliminary data from the study institution indicates that approximately one third of these patients receive transfusion of blood products in the postoperative period. There is growing evidence that hidden blood loss occurring in the postoperative period is substantial and can potentially be attenuated with the administration of Tranexamic Acid (TXA). However, trials on postoperative TXA have been carried out exclusively in adult surgical populations. This is an embedded superiority randomised placebo-controlled patient-/treating team-/assessor-blinded trial comparing tranexamic acid with placebo in reducing blood loss following bilateral bony hip reconstructive surgery in non-ambulatory children with cerebral palsy. Primary objective: to evaluate the impact of postoperative continuous intravenous TXA infusion, compared with placebo in the form of normal saline, on blood loss in non-ambulatory children with cerebral palsy undergoing bilateral VDRO surgery with or without pelvic osteotomy. Secondary objectives: to investigate the safety and tolerability of postoperative tranexamic acid in children with CP undergoing bilateral VDRO surgery with or without pelvic osteotomy, and to evaluate the health economic impact of postoperative tranexamic acid in children with cerebral palsy undergoing bilateral VDRO surgery with or without pelvic osteotomy. To the best of the study team's knowledge this will be the first randomised controlled trial to investigate postoperative intravenous TXA in a paediatric surgical population. Trial population: Non-ambulant children with cerebral palsy undergoing bilateral VDRO surgery with or without pelvic osteotomy. Planned sample size is 52 participants (26 in each group: placebo and intervention). Study setting: Single site electronic medical record (EMR) embedded trial in the software platform EpicTM at The Royal Children's Hospital (RCH). Trial intervention: after cessation of the intraoperative tranexamic acid infusion, and once the patient has been transferred to the recovery bay, the postoperative infusion will commence comprising 10mg/kg/hr intravenous TXA for 24 hours. Placebo: equivalent volume of visually identical normal saline will be infused at the same rate as the TXA. Recruitment: It is anticipated that recruitment will commence in June 2026 and cease August 2028, with the last participant completing 6-month follow up period by April 2029. Participant duration: It is anticipated that duration of participation will be approximately four to six months. The time between initial identification as potentially eligible to date of surgery is three months maximum, length of stay is approximately seven days, and post-operative follow-up is 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Only the research pharmacists dispensing the investigational product or placebo will be aware of treatment allocation. The surgeons, anaesthetists, nursing staff, investigators, participants, and outcome assessors will not be aware of treatment allocation.
入排标准
- 年龄范围
- 4 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children (aged 4 to 16 years)
- •Diagnosis of cerebral palsy (CP). CP is an umbrella term under which many specific diagnoses are captured, and the clinical team at the study institution operates a comprehensive referral network to ensure patients with any relevant diagnoses are included.
- •Gross Motor Function Classification System (GMFCS) levels IV and V, with substantial hip displacement (>40% migration percentage per Australian Hip Surveillance Guidelines (Wynter M, Gibson N, Kentish M, Love S, Thomason P, Willoughby K, et al. Australian hip surveillance guidelines for children with cerebral palsy
- •Australian Academy of Cerebral Palsy and Developmental Medicine. 2014.)), who are on the waitlist for bilateral proximal femoral varus derotational osteotomy (VDRO) +/- unilateral or bilateral pelvic osteotomy.
排除标准
- •Haematological disorder (defined as an active genetic or acquired bleeding disorder)
- •Known hypersensitivity to tranexamic acid (TXA)
- •Children with promyelocytic leukaemia being treated with oral tretinoin will be excluded from the trial because combination with TXA has resulted in fatal thrombotic complications
- •Known coagulation defect
- •Known renal disorder (moderate to severe as per study institution guidelines)
结局指标
主要结局
Mean change between treatment arms in postoperative haemoglobin mass loss, measured on postoperative day 5 or day of discharge (whichever is earlier) and estimated using the HAEmoglobin Mass loss DuRing the periOperative Period (HAEMDROP) formula
时间窗: Day of surgery (within 15 minutes of the end of surgery), Day 5 or day of discharge (whichever is earlier)
HAEMDROP formula: mHb\_loss = BV\*(Hb\_initial - Hb\_final) + (TV \* 200), where: * mHb\_loss = Haemoglobin (Hb) mass loss in grams (g) * BV = Blood volume of the patient in litres (L). For paediatric patients, blood volume is \~75ml/kg. * Hb\_initial = Hb at the start of the period of interest (in grams per litre (g/L)). * Hb\_final = Hb at the end of the period of interest (in grams per litre (g/L)). * VT = volume (in L) of packed red blood cells transfused between Hb\_initial and Hb\_final. * \- 200 = 200g/L, the average haemoglobin level in a unit of blood. Multiplying this by the VT gives the haemoglobin mass transfused (in grams)
次要结局
- Number of clinically significant seizures(Day of surgery until Day 5 post-operatively)
- Duration of hospital stay(Date of surgery, date of discharge from hospital which will be an anticipated average of 8.28 days)
- Duration of paediatric intensive care unit admission(Date of PICU admission through to date of discharge from PICU which will be an anticipated average of 26.5 hours)
- Volume of packed red blood cells transfused(From end of operation to postoperative day 5 or day of discharge (whichever comes first))
- Incidence of surgical wound infections - superficial incisional surgical site infection(Day of surgery through to 30 days following surgery)
- Incidence of surgical wound infections - deep incisional surgical site infection(Day of surgery through to 90 days following surgery)
- Incidence of venous thromboembolism events requiring treatment(Day of surgery through to Day 5 post-surgery)
- Changes in in quality of life, measured in quality-adjusted life years (QALYs)(Preoperatively, 3 months postoperatively, 6 months postoperatively)
- Changes in quality of life(Preoperatively, 3 months postoperatively, 6 months postoperatively)