Randomized, Double-blind, Placebo-controlled, Parallel-group Pilot Study to Assess Efficacy, Safety and Pharmacokinetics of 2 Schedules of Reparixin in the Prevention of Delayed Graft Function After Kidney Transplant in High Risk Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 9
- 主要终点
- Creatinine Clearance (CrCl) in the Immediate Post-transplant Period
研究概览
简要总结
The chemokine CXCL8 plays a key role in the recruitment and activation of polymorphonuclear neutrophils in post-ischemia reperfusion injury after solid organ transplantation. Reparixin is a novel, specific inhibitor of CXCL8. This study is configured to explore the safety and efficacy of reparixin in preventing the delayed graft function (DGF) after kidney transplantation.
详细描述
Delayed graft function (DGF) is the most common allograft complication in the immediate kidney post-transplant period, affecting 25-35% of all patients who receive a cadaver graft, but rates up to 50% have been reported, especially in recipients of kidneys from marginal donors. It is an important clinical complication as it requires dialysis, prolongs hospitalisation, raises the cost of transplantation, and makes more difficult the management of immunosuppressive therapy. Although the effects of DGF on long-term graft function are still debated, there is overall increasing evidence that DGF reduces long-term graft survival. Moreover, given the well documented impact of acute rejection on long-term graft survival, it is conceivable that DGF and acute rejection synergize in negatively influencing long-term graft survival. Kidney reperfusion, after long cold ischemia period, is associated with an inflammatory reaction characterized by massive polymorphonuclear leukocyte (PMN) infiltration both at the glomerular and tubular levels. The importance of CXCL8 in recruiting PMN in kidney tissue during the ischemic time and after reperfusion has been clearly documented.
The efficacy of reparixin in preventing PMN infiltration and tissue damage in rat models of kidney transplantation and lung transplantation, as well as the safety shown in human phase 1 studies, provide the rationale for a clinical study aimed at evaluating the effect of reparixin in preventing DGF after kidney transplantation
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients accepted and listed for renal transplantation due to end stage renal disease (ESRD)
- •Planned isolated single kidney transplant from a non-living donor with brain death
- •Recipients of a kidney maintained in cold storage
- •Recipients at risk of developing DGF
- •Planned induction with steroids + mycophenolate mofetil (MMF) or mycophenolic acid + biological induction
- •Patient willing and able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations
- •Patient given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care
排除标准
- •Recipients of an intended multiple organ transplant
- •Recipients of a kidney from a living donor
- •Recipients of a kidney from a non-heart beating donor
- •Recipients of double kidney transplant
- •Re-transplant >2
- •Recipients of a kidney maintained by pulsatile machine perfusion
- •Concurrent sepsis
- •Recipients with hepatic dysfunction at the time of transplant
- •Clinical contraindications to central line access, or arteriovenous fistula, if any, not suitable for infusion of investigational product
- •Hypersensitivity to non steroidal anti-inflammatory drugs (NSAIDs)
- •Patients simultaneously participating in any other clinical trials involving an investigational drug not yet authorized for use in kidney transplant
- •Pregnant or breast-feeding women
研究组 & 干预措施
reparixin group - continuous infusion
Continuous iv infusion into a (high flow) central vein (or through an arterio-venous fistula) by an infusion pump.
A dose of 2.772 mg/kg/h was administered for12 hours.
干预措施: Reparixin continuous infusion (Drug)
reparixin group - intermittent infusion
Intermittent iv infusion into a (high flow) central vein (or through an arterio-venous fistula) by an infusion pump.
A dose of 2.244 mg/kg was administered over a 30-minute period, followed by a 1.5-hour interval. Twelve doses were administered over a total period of 22.5 hours.
干预措施: reparixin intermittent infusion (Drug)
placebo infusion
Continuous/intermittent iv infusion of a volume/schedule matched saline into a (high flow) central vein (or through an arterio-venous fistula) by an infusion pump.
干预措施: placebo infusion (Other)
结局指标
主要结局
Creatinine Clearance (CrCl) in the Immediate Post-transplant Period
时间窗: 1-3 and 10-12 hours post allograft reperfusion
CrCl was determined by two 60 minute urine collections, during the time intervals 1-3 and 10-12 hours of allograft reperfusion. Blood was withdrawn at the midpoint of each urine collection. CrCl at each timepoint was calculated according to the formula: creatinine clearance (mL/minutes) = urine creatinine (mmol/L) x urine volume (mL) / serum creatinine (mmol/L) x time of collection (minutes) An average was to be calculated from the two 60 minute values in each interval.
次要结局
- Renal Function Tests - Serum Creatinine(daily up to day 7 post-transplant or hospital discharge)
- Acute Rejection Episodes at Month 6 and Between Month 6 and Month 12(at Month 6 and between Month 6 and Month 12)
- Renal Function Tests - Calculated Glomerular Filtration Rate(from Day 1 up to 7 days post-transplant or up to hospital discharge)
- Renal Function Tests - Urine Output(from Day 1 up to 7 days post-transplant or up to hospital discharge)
- Number of Patients Requiring Dialysis Within 7 Days Post-transplant(up to day 7 post-transplant)
- Duration of Hospital Stay(first 30 days post-transplant)
- Graft Survival Rate(at Month 1, Month 6 and Month 12)
- Mortality(first 30 days post-transplant)
- Serum Creatinine at Month 1, Month 6 and Month 12(at Month 1, Month 6 and Month 12)
- Number of Days on Dialysis Before Resuming Kidney Function(up to Day 7 post-transplant)
- Number of Patients With Immediate, Slow and Delayed Graft Function(day 5 post-transplant)
- Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12(at Month 1, Month 6 and Month 12)
- Patient Survival Rate(at Month 1, Month 6 and Month 12)