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Impact of a Treatment With Angiotensin Receptor Blocker on Outcome After Acute Kidney Injury in Patients Discharged From the ICU. (START-or-NOT)

Primary Purpose

Acute Kidney Injury

Status

Recruiting

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

IRBESARTAN, tablet, 150 mg

Placebo, tablet, 150 mg

About this trial

This is an interventional treatment trial for Acute Kidney Injury focused on measuring Angiotensin-Converting-Enzyme Inhibitor, angiotensin-receptor blockers

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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 (changes in serum creatinine < 26 micromol/L or < 25%) among patients ready to be discharged from the ICU or within 30 days after 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.

Exclusion Criteria:

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)

Sites / Locations

Hospital LariboisièreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

IRBESARTAN

Placebo

Arm Description

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 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.

Outcomes

Primary Outcome Measures

Time to MACE (major adverse cardiovascular events)

cardiovascular events will be defined as: acute heart failure, stroke, acute coronary syndrome

Secondary Outcome Measures

Occurrence of chronic kidney disease

kidney disease defined as eGFR <60 ml/min/1.73m2

Albuminuria>0.3 g/day one year after ICU discharge

Chronic kidney disease staging

Change in Chronic kidney disease staging

New episode of acute kidney injury requiring hospitalization

Acute kidney injury according to the KDIGO criteria

Hyperkalemia >6 mmol/L

Death

Full Information

NCT ID

NCT05272878

First Posted

January 10, 2022

Last Updated

December 7, 2022

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT05272878

Brief Title

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

Acronym

START-or-NOT

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Recruiting

Study Start Date

November 22, 2022 (Actual)

Primary Completion Date

June 22, 2025 (Anticipated)

Study Completion Date

June 22, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Kidney Injury

Keywords

Angiotensin-Converting-Enzyme Inhibitor, angiotensin-receptor blockers

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Masking Description

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

Allocation

Randomized

Enrollment

508 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

IRBESARTAN

Arm Type

Active Comparator

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

IRBESARTAN, tablet, 150 mg

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo, tablet, 150 mg

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time to MACE (major adverse cardiovascular events)

Description

cardiovascular events will be defined as: acute heart failure, stroke, acute coronary syndrome

Time Frame

Within the year after randomization

Secondary Outcome Measure Information:

Title

Occurrence of chronic kidney disease

Description

kidney disease defined as eGFR <60 ml/min/1.73m2

Time Frame

one year after ICU discharge

Title

Albuminuria>0.3 g/day one year after ICU discharge

Time Frame

one year after ICU discharge

Title

Chronic kidney disease staging

Time Frame

One year after randomization

Title

Change in Chronic kidney disease staging

Time Frame

One year after randomization

Title

New episode of acute kidney injury requiring hospitalization

Description

Acute kidney injury according to the KDIGO criteria

Time Frame

within one year after randomization

Title

Hyperkalemia >6 mmol/L

Time Frame

within one year after randomization

Title

Death

Time Frame

within one year after randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 (changes in serum creatinine < 26 micromol/L or < 25%) among patients ready to be discharged from the ICU or within 30 days after 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. Exclusion Criteria: 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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Etienne GAYAT, MD-PhD

Phone

01 49 95 80 84

Ext

+33

etienne.gayat@aphp.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Matthieu Legrand, MD-PhD

matthieu.m.legrand@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Etienne Gayat, MD-PhD

Organizational Affiliation

APHP-Hôpital Lariboisière

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Matthieu Legrand, MD-PhD

Organizational Affiliation

Departement of Anesthesia and Peri-operative Care, UCSF

Official's Role

Study Director

Facility Information:

Facility Name

Hospital Lariboisière

City

Paris

ZIP/Postal Code

75010

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Etienne GAYAT, MD-PhD

Phone

01 49 95 80 81

Ext

+33

etienne.gayat@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

21814177

Citation

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.

Results Reference

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PubMed Identifier

18223026

Citation

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.

Results Reference

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PubMed Identifier

28406186

Citation

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.

Results Reference

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PubMed Identifier

29766216

Citation

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.

Results Reference

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PubMed Identifier

30422153

Citation

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.

Results Reference

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PubMed Identifier

22473149

Citation

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.

Results Reference

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PubMed Identifier

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Citation

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.

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PubMed Identifier

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Citation

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.

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Citation

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.

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

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