Impact of a Treatment With Angiotensin Receptor Blocker on Outcome After Acute Kidney Injury in Patients Discharged From the ICU.

NCT05272878 | Active Not Recruiting Phase 3

• 1 other identifier: APHP200040
• Study Type: interventional
• Target: 508
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Kidney Injury

Keywords

Angiotensin-Converting-Enzyme Inhibitor; angiotensin-receptor blockers

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• Occurrence of chronic kidney disease

  one year after ICU discharge

• Albuminuria>0.3 g/day one year after ICU discharge

  one year after ICU discharge

• 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

  within one year after randomization

Study Arms (2)

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.

Drug: IRBESARTAN, tablet, 150 mg

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.

Drug: Placebo, tablet, 150 mg

Interventions

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.

IRBESARTAN

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hospital Lariboisière

Paris, 75010, France

Location

Related Publications (10)

• 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.

  PMID: 21814177 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.

  PMID: 18223026 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.

  PMID: 28406186 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.

  PMID: 29766216 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.

  PMID: 30422153 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.

  PMID: 22473149 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.

  PMID: 29773712 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.

  PMID: 29890946 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.

  PMID: 27307250 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.

  PMID: 29162339 BACKGROUND

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Irbesartan; Tablets

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Spiro Compounds; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Etienne Gayat, MD-PhD

  APHP-Hôpital Lariboisière

  PRINCIPAL INVESTIGATOR

• Matthieu Legrand, MD-PhD

  Departement of Anesthesia and Peri-operative Care, UCSF

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: March 10, 2022
• Study Start: November 22, 2022
• Primary Completion: June 27, 2025
• Study Completion (Estimated): June 27, 2026
• Last Updated: September 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)