Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Phase III study Prospective, multicenter, superiority, double-blind, randomized controlled study with two arms (1:1).
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IRBESARTAN | Active Comparator | 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. |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IRBESARTAN, tablet, 150 mg | Drug | 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.Treatment will be continued for 12 months, unless a side effect would occur. |
| Measure | Description | Time Frame |
|---|---|---|
| Time to MACE (major adverse cardiovascular events) | cardiovascular events will be defined as: acute heart failure, stroke, acute coronary syndrome | Within the year after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of chronic kidney disease | kidney disease defined as eGFR <60 ml/min/1.73m2 | one year after ICU discharge |
| Albuminuria>0.3 g/day one year after ICU discharge | one year after ICU discharge |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Etienne Gayat, MD-PhD | APHP-Hôpital Lariboisière | Principal Investigator |
| Matthieu Legrand, MD-PhD | Departement of Anesthesia and Peri-operative Care, UCSF | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Lariboisière | Paris | 75010 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21814177 | Background | Grams ME, Rabb H. The distant organ effects of acute kidney injury. Kidney Int. 2012 May;81(10):942-948. doi: 10.1038/ki.2011.241. Epub 2011 Aug 3. | |
| 18223026 | Background | Burchill L, Velkoska E, Dean RG, Lew RA, Smith AI, Levidiotis V, Burrell LM. Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin-converting enzyme 2 expression. Exp Physiol. 2008 May;93(5):622-30. doi: 10.1113/expphysiol.2007.040386. Epub 2008 Jan 25. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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
| Placebo, tablet, 150 mg | Drug | 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.Treatment will be continued for 12 months, unless a side effect would occur. |
|
| Chronic kidney disease staging | One year after randomization |
| Change in Chronic kidney disease staging | One year after randomization |
| New episode of acute kidney injury requiring hospitalization | Acute kidney injury according to the KDIGO criteria | within one year after randomization |
| Hyperkalemia >6 mmol/L | within one year after randomization |
| Death | within one year after randomization |
| 28406186 | Background | Chou YH, Huang TM, Pan SY, Chang CH, Lai CF, Wu VC, Wu MS, Wu KD, Chu TS, Lin SL. Renin-Angiotensin System Inhibitor is Associated with Lower Risk of Ensuing Chronic Kidney Disease after Functional Recovery from Acute Kidney Injury. Sci Rep. 2017 Apr 13;7:46518. doi: 10.1038/srep46518. |
| 29766216 | Background | Gayat E, Hollinger A, Cariou A, Deye N, Vieillard-Baron A, Jaber S, Chousterman BG, Lu Q, Laterre PF, Monnet X, Darmon M, Leone M, Guidet B, Sonneville R, Lefrant JY, Fournier MC, Resche-Rigon M, Mebazaa A, Legrand M; FROG-ICU investigators. Impact of angiotensin-converting enzyme inhibitors or receptor blockers on post-ICU discharge outcome in patients with acute kidney injury. Intensive Care Med. 2018 May;44(5):598-605. doi: 10.1007/s00134-018-5160-6. Epub 2018 May 15. |
| 30422153 | Background | Brar S, Ye F, James MT, Hemmelgarn B, Klarenbach S, Pannu N; Interdisciplinary Chronic Disease Collaboration. Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With Outcomes After Acute Kidney Injury. JAMA Intern Med. 2018 Dec 1;178(12):1681-1690. doi: 10.1001/jamainternmed.2018.4749. |
| 22473149 | Background | Wang HE, Muntner P, Chertow GM, Warnock DG. Acute kidney injury and mortality in hospitalized patients. Am J Nephrol. 2012;35(4):349-55. doi: 10.1159/000337487. Epub 2012 Apr 2. |
| 29773712 | Background | Go AS, Hsu CY, Yang J, Tan TC, Zheng S, Ordonez JD, Liu KD. Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events. Clin J Am Soc Nephrol. 2018 Jun 7;13(6):833-841. doi: 10.2215/CJN.12591117. Epub 2018 May 17. |
| 29890946 | Background | Lee BJ, Hsu CY, Parikh RV, Leong TK, Tan TC, Walia S, Liu KD, Hsu RK, Go AS. Non-recovery from dialysis-requiring acute kidney injury and short-term mortality and cardiovascular risk: a cohort study. BMC Nephrol. 2018 Jun 11;19(1):134. doi: 10.1186/s12882-018-0924-3. |
| 27307250 | Background | Omotoso BA, Abdel-Rahman EM, Xin W, Ma JZ, Scully KW, Arogundade FA, Balogun RA. Dialysis requirement, long-term major adverse cardiovascular events (MACE) and all-cause mortality in hospital acquired acute kidney injury (AKI): a propensity-matched cohort study. J Nephrol. 2016 Dec;29(6):847-855. doi: 10.1007/s40620-016-0321-6. Epub 2016 Jun 15. |
| 29162339 | Background | Bansal N, Matheny ME, Greevy RA Jr, Eden SK, Perkins AM, Parr SK, Fly J, Abdel-Kader K, Himmelfarb J, Hung AM, Speroff T, Ikizler TA, Siew ED. Acute Kidney Injury and Risk of Incident Heart Failure Among US Veterans. Am J Kidney Dis. 2018 Feb;71(2):236-245. doi: 10.1053/j.ajkd.2017.08.027. Epub 2017 Nov 20. |
| ID | Term |
|---|---|
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077405 | Irbesartan |
| D013607 | Tablets |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D013141 | Spiro Compounds |
| D013777 | Tetrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
Not provided
Not provided