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

September 1, 2025 updated by: Assistance Publique - Hôpitaux de Paris

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

508

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75010
        • Hospital Lariboisière

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 (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.

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: IRBESARTAN, tablet, 150 mg
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.
Placebo Comparator: 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.
Drug: Placebo, tablet, 150 mg
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to MACE (major adverse cardiovascular events)
Time Frame: Within the year after randomization
cardiovascular events will be defined as: acute heart failure, stroke, acute coronary syndrome
Within the year after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of chronic kidney disease
Time Frame: one year after ICU discharge
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
Time Frame: one year after ICU discharge
one year after ICU discharge
Chronic kidney disease staging
Time Frame: One year after randomization
One year after randomization
Change in Chronic kidney disease staging
Time Frame: One year after randomization
One year after randomization
New episode of acute kidney injury requiring hospitalization
Time Frame: within one year after randomization
Acute kidney injury according to the KDIGO criteria
within one year after randomization
Hyperkalemia >6 mmol/L
Time Frame: within one year after randomization
within one year after randomization
Death
Time Frame: within one year after randomization
within one year after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Etienne Gayat, MD-PhD, Aphp-Hopital Lariboisiere
  • Study Director: Matthieu Legrand, MD-PhD, Departement of Anesthesia and Peri-operative Care, UCSF

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 22, 2022

Primary Completion (Actual)

June 27, 2025

Study Completion (Estimated)

June 27, 2026

Study Registration Dates

First Submitted

January 10, 2022

First Submitted That Met QC Criteria

February 28, 2022

First Posted (Actual)

March 10, 2022

Study Record Updates

Last Update Posted (Estimated)

September 8, 2025

Last Update Submitted That Met QC Criteria

September 1, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP200040

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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