A Multicenter, Open-label, Randomized Pilot Clinical Study of Efficacy and Safety of Reparixin for Prevention of Early Allograft Dysfunction in Patients Undergoing Orthotopic Liver Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 40
- 试验地点
- 7
- 主要终点
- Incidence of EAD (Early Allograft Dysfunction) Within 7 Days After OLT (PP Population)
研究概览
简要总结
The objective of the study is to evaluate the efficacy and safety of Reparixin treatment (2.772 mg/kg body weight/hour intravenous continuous infusion for 7 days) based on incidence of early allograft dysfunction within the first 7 days after orthotopic liver transplantation (OLT) and overall indicators of allograft dysfunction in the early postoperative period (within 14 days after the OLT).
详细描述
The study is a phase 2, multicenter, open-label, randomized pilot study to evaluate the efficacy and safety of Reparixin for prevention of early allograft dysfunction in patients undergoing orthotopic liver transplantation.
All the patients who participated in the study received standard immunosuppressive therapy in accordance with the Russian Transplant Society Guidelines for liver transplantation (2013). The study was planned to be conducted at 5-8 transplantation sites in Russia and Belarus. Recruitment was competitive among the study sites so that patients were screened and if eligible, randomized consecutively until the randomization was stopped.
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
- None
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
- •Male and female patients aged 18 years and older needing a whole organ OLT, listed on the waiting list for liver transplantation.
- •Severity score of the initial condition of the patient (hepatocellular dysfunction) according to the scales of Child-Turcotte-Pugh ≥ 7 points or MELD 15-40 points (or both).
- •The possibility of insertion of a central catheter for infusion of the study drug.
- •Signed Patient Informed Consent Form.
- •Ability to comply with all the requirements of the protocol.
- •Consent to use adequate contraception means throughout the study. The adequate contraception methods include use of condom with spermicide.
排除标准
- •Patients with any of the following conditions shall not be included in the study:
- •Split-liver transplantation or transplantation from a living donor.
- •Re-transplantation or multivisceral transplantation.
- •The presence of extrahepatic tumor foci or sepsis.
- •Gastrointestinal bleeding caused by portal hypertension within 3 months prior to screening.
- •BMI less than 18.5 or more than 40 kg/m
- •HIV infection.
- •Significant cardiovascular disease at the present time or within 6 months prior to screening, including: class III or IV chronic heart failure (the New York Heart Association), myocardial infarction, unstable angina, hemodynamically significant cardiac arrhythmias, ischemic or hemorrhagic stroke, uncontrolled arterial hypertension.
- •Preoperative renal impairment (glomerular filtration rate estimated with the Cockcroft-Gault formula ≤ 45 mL/min).
- •Significant, in the opinion of the Investigator, drug or alcohol abuse within 6 months prior to screening.
- •Hypersensitivity to:
- •ibuprofen or to more than one non-steroidal anti-inflammatory drug (NSAID),
- •more than one medication belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib; hypersensitivity to sulphanilamide antibiotics alone (e.g. sulfamethoxazole) does not qualify for exclusion.
- •Pregnant or lactating women, or women planning a pregnancy during the clinical study, fertile women not using adequate contraception methods.
- •Participation in another clinical study currently or within 30 days prior to screening, use of any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to screening.
- •The patient's and his/her relatives' failure to understand the need for lifelong immunosuppressive therapy, as well as the risk and difficulty of the pending operation and the subsequent dynamic treatment.
- •Inability to read or write; unwillingness to understand and comply with the procedures of the study protocol; failure to comply with the treatment, which, in opinion of the Investigator, may affect the results of the study or the patient's safety and prevent the patient from further participation in the study; any other associated medical or serious mental conditions that make the patient unsuitable for participation in the clinical study, limit the validity of informed consent or may affect the patient's ability to participate in the study.
研究组 & 干预措施
Reparixin
Patients in the group of the study therapy received Reparixin at dose of 2.772 mg/kg/hour for 7 days (168 hours). The prepared solution of Reparixin 11 mg/ml was administered as a continuous infusion into a central vein using an automatic infusion pump that provides a constant rate of infusion.
All patients of the study received standard immunosuppressive therapy in accordance with the Russian Transplant Society Guidelines for liver transplantation.
干预措施: Reparixin (Drug)
Control
The patients, who were randomized in the control group, did not receive any study therapy. All patients of the study received standard immunosuppressive therapy in accordance with the Russian Transplant Society Guidelines for liver transplantation.
干预措施: Control (Other)
结局指标
主要结局
Incidence of EAD (Early Allograft Dysfunction) Within 7 Days After OLT (PP Population)
时间窗: within 7 day after the OLT
Assessment of the frequency of early allograft disfunction (EAD) after orthotopic liver transplantation (OLT) (Day 7 of Week 1) among patients who received Reparixin and patients in the control group. EAD was defined according to standard criteria as maximum Alanine Transferase (ALT) or Aspartate Transferase (AST) levels on days 1-7 of \>2000 U/L, day 7 Bilirubin level ≥10 mg/dl, or a day 7 International Normalized ratio (INR) ≥1.6. Taking into account that 5 out of 22 patients in the Reparixin group experienced EAD during the first stage of the study, according to the Protocol and the DMC conclusion, it was decided on the early termination of the study.
Incidence of EAD (Early Allograft Dysfunction) Within 7 Days After OLT (mITT Population)
时间窗: within 7 day after the OLT
Assessment of the frequency of early allograft disfunction after orthotopic liver transplantation (OLT) (Day 7 of Week 1) among patients who received Reparixin and patients in the control group. EAD was defined according to standard criteria as maximum Alanine Transferase (ALT) or Aspartate Transferase (AST) levels on days 1-7 of \>2000 U/L, day 7 Bilirubin level ≥10 mg/dl, or a day 7 International Normalized ratio (INR) ≥1.6. Please note that taking into account that 5 out of 22 patients in the Reparixin group experienced EAD during the first stage of the study, according to the Protocol and the DMC conclusion, it was decided on the early termination of the study.
次要结局
- Number of Patients With/Without Primary Allograft Nonfunction Within 7 Days After OLT(Within 7 days after OLT)
- Number of Patients With/Without Overall Indicators of Allograft Dysfunction During the Early Postoperative Period(Within 14 days after OLT)
- Overall Indicators of the Allograft Dysfunction During the Early Postoperative Period - Extracorporeal Detoxification(Within 14 days after OLT)
- Frequency of Identification of Laboratory Examination Values(within 3 day after the OLT)
- Number of Patients With Early Allograft Dysfunction (EAD) in Case of Transplantation of Donor Organs, by the Degree of Steatosis(Within 14 days after OLT)
- Number of Patients With EAD in Case of Transplantation of Donor Organs Differing by the Time (in Hours) of Allograft Removal From the Donor and up to Its Reperfusion (Duration of Cold Ischemia)(Within 14 days after OLT)
- Number of Patients With EAD in Case of Transplantation of Donor Organs Differing by the Duration (in Min) of Warm Ischemia(Within 14 days after OLT)
- Number of Patients With EAD in Transplantation From Donors Having Additional Adverse Factors(Within 14 days after OLT)
- Number of Patients With EAD in Transplantation With Regard to the Interval (in Hours) Between the Diagnosis of Brain Death and Removal of the Liver Graft From a Donor(Within 14 days after OLT)
- Number of Patients With EAD in Transplant Recipients With Each of the Different Liver Disease Etiology(Within 14 days after OLT)
- Incidence of Early Allograft Dysfunction (EAD) in Transplant Recipients With Liver Diseases of Different Etiology and With Different Baseline Characteristics(Within 14 days after OLT)
- The Number of Patients With EAD in Transplant Recipients With Liver Diseases (HBV and HCV Virus) and With Different Baseline Characteristics(Within 14 days after OLT)
- Incidence of Early Allograft Dysfunction in Transplant Recipients (Creatinine Clearance, ClCr)(Within 14 days after OLT)
- Incidence of Early Allograft Dysfunction in Transplant Recipients - Severity of Recipient's Liver Disease Through MELD Index(Within 14 days after OLT)
- Number of Patients With EAD in Transplant Recipients Via Child-Turcotte-Pugh Score (CTP)(Within 14 days after OLT)
- Time to Liver Function Normalization of Liver Function Parameters(Within 1 Year after OLT)
- Patient Survival Within 1 Year After OLT(within 1 year after OLT)
- Mortality Within 1 Year After the OLT(Within 1 Year after OLT)
- The Incidence of Hyperacute, Acute and Chronic Liver Allograft Rejection .(Within 1 Year after OLT)
- Summary of Adverse Events up to 1 Year After the OLT(up to 1 year after the OLT)