An open label pilot RCT to demonstrate the superiority of high volume over standard volume therapeutic plasma exchange in pediatric patients with acute liver failure and hepatic encephalopathy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Proportion of patients surviving at day 14 from randomization
研究概览
简要总结
Pediatric acute liver failure (PALF) is a complex and rapidly progressive condition. Despite advancements in critical care, it is associated with high morbidity and mortality in the absence of liver transplant. In the Indian setting, liver transplant is rare. Hence, extracorporeal liver support systems (ELSS) are used as bridge therapy to prolong survival of the patient till the time transplant becomes feasible. Sometimes, especially in drug or toxin associated ALF, patient can even recover spontaneously with these therapies. Therapeutic plasma exchange (TPE) is one of the most prevalent ELSS and is currently recommended by Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN) as a bridge therapy to liver transplant in PALF. However, there is no consensus regarding the volume of plasma that needs to be used. Evidence on this topic from pediatric population is chiefly from retrospective case series or cohorts. Moreover, patient having subacute or chronic liver disease have not always been excluded in these studies. Hence, this prospective randomized pilot study with strict inclusion criteria is planned to compare standard volume (1-1.5 times) and high volume (2-3 times) TPE in pediatric patients with ALF and hepatic encephalopathy in whom TPE is indicated. The outcomes of the study will provide useful information on whether high volume TPE is indeed necessary, or standard volume TPE is associated with outcomes similar to high volume TPE, in patients with pediatric ALF and hepatic encephalopathy in whom TPE is indicated. This information will provide evidence to refine protocols for extracorporeal therapies for pediatric ALF. The study will also inform whether performing TPE in high volumes is feasible or not.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 4.00 Year(s) 至 18.00 Year(s)（—）
- 性别
- All
入选标准
- •Children, both male and female, 4-18 years of age with: Pediatric acute liver failure as defined by PALF – Study group as i) hepatic-based coagulopathy, defined as a prothrombin time (PT) ≥ 15 sec or international normalized ratio (INR) ≥ 1.5 not corrected by vitamin K in the presence of clinical hepatic encephalopathy (HE), or a PT ≥ 20 sec or INR ≥ 2.0 regardless of the presence or absence of clinical hepatic encephalopathy (HE); (ii) biochemical evidence of acute liver injury; (iii) and no known evidence of chronic liver disease Interval from jaundice to encephalopathy 8-28 days Therapeutic Plasma Exchange indicated by (i) INR ≥2.5 and (ii) hepatic encephalopathy of any grade (1-4) Written informed parental consent (patient’s assent will not be feasible as he/she will be in hepatic encephalopathy).
排除标准
- •Body weight less than or equal to 8 kg Known chronic liver disease of any etiology Presenting more than 2 weeks after the onset of acute liver failure AB blood group Prior enrollment in the study Anticipated delay of more than 24 hours in initiating therapeutic plasma exchange Hemodynamic instability despite use of 2 or more than 2 vasoactive drugs in maximum doses Decision of physician to not escalate therapy.
结局指标
主要结局
Proportion of patients surviving at day 14 from randomization
时间窗: At day 14
次要结局
- Change from baseline, to 24-hr after 1 session of membrane filtration based therapeutic plasma exchange (mTPE) (day 2-3), 24-hr after 3 sessions of mTPE (day 4-5), and on day 7, in:(i. Grade of hepatic encephalopathy;)
- Number and types of adverse events, including serious adverse events (SAE), CTCAE classification and WHO-UMC categorization of relatedness to TPE, by end of 3 mTPE sessions(Ongoing monitoring)
- Feasibility of procedure, as determined by average plasma volumes truly exchanged with fresh frozen plasma (FFP) at the end of 3 mTPE sessions(At the end of 3 mTPE sessions)
- Proportions with native liver survival(At day 14)
研究者
Aditya Gupta
All India Institute of Medical Sciences New Delhi