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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

22 Nov 2022 → ongoing

Decision date (initial)

2024-10-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Assitance Publique Hopitaux de Paris

External identifiers

EU CT number

2024-515845-40-00

EudraCT number

2020-000414-16

ClinicalTrials.gov

NCT05272878

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the impact of the RAASi on cardiovascular and global outcome during the year following ICU or Transitional Care Unit (TCU) discharge in patients who developed an AKI and totally or partially recovered

Secondary objectives 4

1. To evaluate the impact of RAASi initiation on renal outcome after ICU or TCU discharge
2. To evaluate the impact of RAASi initiation on new hospitalizations for major cardiovascular events
3. To evaluate the impact of RAASi initiation on potential side effect of the treatment (safety)
4. To identify among the patient's characteristics the factors of response to treatment, including the use of the biological collection built up at inclusion and at the end of the study

Conditions and MedDRA coding

Acute kidney injury

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female patients ≥ 18 years of age
2. Met criteria for acute kidney injury during the ICU stay (according to the KDIGO criteria)
3. 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 TCU. and within 30 days after their discharge.
4. Patient affiliated to a Social Security System
5. Women of childbearing potential and men must agree, to use adequate and highly effective contraception, until the end of the research.

Exclusion criteria 16

1. Patient treated with ACEi or ARB before ICU admission
2. Patient for whom treatment with ACEi or ARA is strongly recommended according to the international guidelines (ie patients with congestive heart failure and persistent dyspnea with LVEF<40%, patients with diabetes mellitus AND [either albuminuria > 30mg /g creatininuria or hypertension associated with microalbuminuria or hypertension associated with eGFR < 60 ml/min) known before ICU admission
3. Hyperkalemia > 5 mmol/L at ICU discharge
4. Systolic blood pressure <100 mmHg at ICU discharge
5. 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
6. Oral route impossible
7. Pregnancy
8. Breast feeding
9. Patients chronically treated with Aliskiren
10. Known hypersensitivity to the active substance or to one of its excipients and in particular to lactose
11. Patients with known primary hyperaldosteronism
12. Patients with known severe and symptomatic aortic stenosis, mitral stenosis or obstructive hypertrophic cardiomyopathy.
13. Patients treated with lithium
14. 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.
15. Patients deprived of liberty by a judicial or administrative decision
16. Patient to a legal protection measure (guardianship, curatorship and safeguard of justice)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the trial is the time to MACE (major adverse cardiovascular events), i.e. a composite outcome composed of all-cause mortality and all unscheduled hospital readmission for cardiovascular events (acute heart failure, stroke, acute coronary syndrome) during the year following ICU or TCU discharge

Secondary endpoints 8

1. Albuminuria >0.3 g/day one year after ICU or TCU discharge
2. Occurrence of chronic kidney disease one year after ICU or TCU discharge defined as eGFR <60 ml/min/1.73m2
3. Decrease of estimated glomerular filtration from baseline to one year after enrollment
4. Change in Chronic kidney disease staging one year after enrollment
5. New episode of acute kidney injury (according to the KDIGO criteria) requiring hospitalization
6. Hyperkalemia >6 mmol/L
7. Death
8. Biological collection built up at inclusion and at the end of the study

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Etienne Gayat

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Etienne Gayat

Locations

1 EU/EEA country · 32 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications