Impact of a Treatment With Angiotensin Receptor Blocker on Outcome After Acute Kidney Injury in Patients Discharged From the ICU "START-or-NOT Trial". A Prospective, Randomized, Double Blinded, Multicenter Study
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 508
- 试验地点
- 1
- 主要终点
- Time to MACE (major adverse cardiovascular events)
研究概览
简要总结
The patients discharged from intensive care units (ICU) have a high incidence of cardiovascular events and mortality rate during the year following ICU discharge. Among patients admitted to the ICU, patients with acute kidney injury (AKI) display high risk of such events. The investigators furthermore demonstrated that AKI could induce remote cardio-vascular injury and fibrosis, which may be involved in the poor prognosis of AKI. Strategies that may prevent the cardiovascular consequences of AKI in most severe patients (i.e. post-AKI ICU survivors) may therefore improve long term outcomes.
AKI has been associated with activation of the renin-angiotensin-aldosterone system (RAAS). Activation of the RAAS has been further associated with long-term health consequences especially with cardiovascular damages. Potential protective effects of RAASi following acute injury have been reported in observational studies. With this randomized controlled trial, the investigators aim at investigating the impact of treatment with RAAS inhibitors after AKI on cardiovascular and kidney outcomes.
详细描述
Phase III study Prospective, multicenter, superiority, double-blind, randomized controlled study with two arms (1:1).
- Inclusion of patients who are discharged alive (or ready to be discharged) from ICU or acute care and developed acute kidney injury during the ICU stay (according to the KDIGO criteria) - and signing of the consent to participate at this research
- Enrolled patients will be randomly assigned to one of the two study groups once their renal function has stabilized for at least 48 hours and within 30 days from ICU or acute care discharge. Patients randomized will be stratified according to the center and the severity of AKI during ICU stay (KDIGO 1 vs KDIGO 2 or 3)
- All patients with have a clinical examination and biological visit (i.e. serum creatinine, potassium, and NT-ProBNP) 7(+/-2) days after inclusion, at 2 months, 6 months and at 12 months. Microalbuminuria will be further measure at inclusion and 12 months. In the control and treatment group, treatment will be upgraded to 2 pills (IRBESARTAN 150 mg or Placebo) if Serum creatinine has not risen by more than 30% since previous visit and no hyperkalemia and no hypotension are noticed. Treatment management will be performed by intensivists, nephrologists or cardiologists involved in the protocol.
Biological collection
A plasma and urine collected as part of the study will be stored in a biological sample collection at inclusion and at the end of the study.
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
- Double (Participant, Investigator)
盲法说明
Treatments will be conditioned and labelled by the Contract manufacturing organization AGEPS according to a list provided by an independent person and assigning a treatment arm to each treatment number.
Randomization and treatment numbers lists are kept strictly confidential until the time of unblinding, and will not be accessible by anyone involved in the study, with the exception of the independent, unblinded statistician approving the randomization scheme; the study will be kept blinded to patients, investigators and study personnel also during the entire study period; The identification of treatment will be concealed by the use of a matching placebo to the study product that will be provided in boxes identical in packaging, labeling and appearance
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient between 18 and 75 years old
- •Met criteria for acute kidney injury during the ICU stay (according to the KDIGO criteria)
- •After their renal function has stabilized for at least 48 hours (Serum creatinine decreasing or not increasing more than 26 micromol/L or 25%) among patients ready to be discharged from the ICU or acute careTCU. and within 30 days after their ICU discharge.
- •Signed informed consent
- •Patients affiliated to a Social Security System
- •Women of childbearing potential and men must agree, to use adequate and highly effective contraception, until the end of the research.
排除标准
- •Patient treated with ACEi or ARB before ICU admission
- •Patient for whom treatment with ACEi or ARB is strongly recommended according to the international guidelines at discharge (i.e. patients with congestive heart failure and persistent dyspnea with LVEF<40%,, patients with diabetes mellitus and either albuminuria > 300 µg/g creatininuria or hypertension associated with microalbuminuria or hypertension associated with eGFR < 60 ml/min) known before ICU admission.
- •Hyperkalemia>5 mmol/L
- •Systolic blood pressure <100 mmHg
- •Patient with severe renal failure, as defined by estimated glomerular filtration rate creatinine clearance < 15 ml/min/1.73m2), requiring renal replacement therapy at ICU discharge
- •Oral route impossible.
- •Pregnancy
- •Breast feeding
- •Patients chronically treated with Aliskiren
- •Known hypersensitivity to the active substance or to one of its excipients and in particular to lactose
- •Patients with known primary hyperaldosteronism
- •Patients with known severe and symptomatic aortic stenosis, mitral stenosis or obstructive hypertrophic cardiomyopathy.
- •Patients treated with lithium
- •Patient undergoing psychiatric care
- •Inability to consent due to psychiatric disorders defined as psychiatric disorders or patient with a mental state requiring immediate care with either by constant medical surveillance justifying hospitalization, or regular medical follow-up justifying specific treatment
- •Patient deprived of liberty by a judicial or administrative decision
- •Patient to a legal protection measure (guardianship, curatorship and safeguard of justice)
研究组 & 干预措施
IRBESARTAN
IRBESARTAN will be introduced at 150 mg orally one daily, with a progressive increase to 300 mg a day, at 7 days or 2 months follow-up visit, based on clinical and biological tolerance. Treatment will be continued for 12 months, unless a side effect would occur.
干预措施: IRBESARTAN, tablet, 150 mg (Drug)
Placebo
Placebo will be introduced at 150 mg orally one daily, with a progressive increase to 300 mg a day, at 7 days or 2 months follow-up visit, based on clinical and biological tolerance. Treatment will be continued for 12 months, unless a side effect would occur.
干预措施: Placebo, tablet, 150 mg (Drug)
结局指标
主要结局
Time to MACE (major adverse cardiovascular events)
时间窗: Within the year after randomization
cardiovascular events will be defined as: acute heart failure, stroke, acute coronary syndrome
次要结局
- Occurrence of chronic kidney disease(one year after ICU discharge)
- Chronic kidney disease staging(One year after randomization)
- Change in Chronic kidney disease staging(One year after randomization)
- Albuminuria>0.3 g/day one year after ICU discharge(one year after ICU discharge)
- New episode of acute kidney injury requiring hospitalization(within one year after randomization)
- Hyperkalemia >6 mmol/L(within one year after randomization)
- Death(within one year after randomization)