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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
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

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

First Posted
January 10, 2022
Last Updated
December 7, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
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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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

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
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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, based on clinical and biological tolerance. Treatment will be continued for 12 months, unless a side effect would occur.
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
No
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
Email
etienne.gayat@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Matthieu Legrand, MD-PhD
Email
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
Email
etienne.gayat@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD
No
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
background
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
background
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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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.
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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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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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Impact of a Treatment With Angiotensin Receptor Blocker on Outcome After Acute Kidney Injury in Patients Discharged From the ICU.

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