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Trial registered on ANZCTR

Registration number

ACTRN12621000281897

Ethics application status

Approved

Date submitted

1/01/2021

Date registered

12/03/2021

Date last updated

19/12/2022

Date data sharing statement initially provided

12/03/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

Acute Renal effects of Angiotensin II Management In Shock in the Intensive Care Unit (ARAMIS-ICU)

Scientific title

A prospective study of the renal effects of angiotensin II management in critically ill patients with distributive shock

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

ARAMIS-ICU

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Distributive shock

Condition category

Condition code

Renal and Urogenital

Kidney disease

Cardiovascular

Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Angiotensin II administered continuously via intravenous infusion at a dose range of 5-40 ng/kg/min, with the administered dose titrated to achieve a MAP >65 until resolution of shock or for a maximum of 7 days. After 7 days, patients will be transitioned to noradrenaline.

Patients in the intervention arm may receive noradrenaline or metaraminol prior to angiotensin II prior to initiation of angiotensin II where this therapy was initiated in the operating theatre, emergency department, or on the ward prior to ICU transfer. However, patients who have received >24 hours of noradrenaline or metaraminol prior to enrolment are ineligible for the study.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Noradrenaline administered continuously via intravenous infusion at a dose range of 1-50 mcg/kg/min with the administered dose titrated to achieve a MAP >65 until resolution of shock.

Patients who receive noradrenaline as a bridge to establishing angiotensin II therapy (as described in the intervention panel above) are considered to be in the intervention arm rather than the control arm.

Control group

Active

Outcomes

Primary outcome [1]

Peak serum creatinine (umol/L)

Timepoint [1]

Measured at baseline and every 4-6 hours post-commencement of infusion for a maximum of 7 days or until ICU discharge

Secondary outcome [1]

The number of patients who develop either new or progressive KDIGO acute kidney injury (as assessed using biochemical data obtained during hospitalisation) following initiation of intervention or control infusions (this is a composite outcome).

Timepoint [1]

7 days post-commencement of infusion

Secondary outcome [2]

The number of patients who require renal replacement therapy following initiation of intervention or control infusions as assessed using the patient medical record

Timepoint [2]

7 days post-commencement of infusion

Secondary outcome [3]

Average daily urine output (L/day) as assessed using the patient medical record

Timepoint [3]

Daily for 7 days post-commencement of infusion

Secondary outcome [4]

Cumulative fluid balance (L) as assessed using the patient medical record

Timepoint [4]

7 days post-commencement of infusion

Secondary outcome [5]

Lowest mean arterial pressure as assessed using an arterial line

Timepoint [5]

Assessed at baseline and hourly until the cessation of the infusion or for a maximum of 7 days

Secondary outcome [6]

The number of patients who require invasive ventilation following initiation of intervention or control infusions as assessed using the patient medical record

Timepoint [6]

7 days post-commencement of infusion

Secondary outcome [7]

ICU length of stay as assessed using the patient medical record

Timepoint [7]

Patient discharge from ICU

Secondary outcome [8]

Hospital length of stay as assessed using the patient medical record

Timepoint [8]

Patient discharge from hospital

Secondary outcome [9]

Days alive and free of renal replacement therapy (composite) as assessed using the patient medical record

Timepoint [9]

28 days post-commencement of infusion

Secondary outcome [10]

The number of patients who die during their ICU stay as assessed using the patient medical record

Timepoint [10]

ICU discharge

Secondary outcome [11]

The number of patients who die in hospital as assessed using the patient medical record

Timepoint [11]

Hospital discharge

Secondary outcome [12]

The number of patients who die within 28 days of initiation of the infusion as assessed using the patient medical record

Timepoint [12]

28 days post-commencement of infusion

Secondary outcome [13]

The number of patients who develop a thromboembolic event (DVT, PE, elevated troponin) as assessed using the patient medical record

Timepoint [13]

7 days post-commencement of infusion

Eligibility

Key inclusion criteria

• Adults aged > 18 years
• Vasodilatory shock (MAP <65 mmHg)
• Central venous access and an arterial line present
• Indwelling urinary catheter
• Expected to require vasopressor support for at least 24 hours
• Informed consent provided by the patient or medical treatment decision-maker

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

• Cardiac surgery patients
• >24 hours noradrenaline or metaraminol prior to enrolment
• Chronic haemodialysis or peritoneal dialysis
• Not receiving venous thromboembolism prophylaxis
• Venous thromboembolism or pulmonary embolus in the last 6 months
• Expected survival <24 hours
• Suspected or confirmed pregnancy

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Other

Other design features

This is a sequential period study. All patients meeting all of the inclusion criteria and none of the exclusion criteria will receive the intervention during the first period. All patients meeting all of the inclusion criteria and none of the exclusion criteria will receive the control during the second period.

Phase

Phase 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

Statistical analysis will be performed using computerized software (Stata MP/16.0, StataCorp, College Station, Texas, USA). Baseline characteristics will be reported as frequencies and percentages, means and standard deviation, or medians and interquartile ranges. Summary statistics to compare baseline characteristics will include t-test, chi squared test, and Wilcoxon rank sum test, as dictated by data type. The primary outcome will be reported using multivariable linear regression models. Secondary outcomes will be explored using multivariable linear (continuous outcomes) and logistic (binary outcomes) regression models. No imputation will be performed for missing data. Pre-specified secondary analyses will examine whether baseline and 24 hour renin level can identify angiotensin II patients most likely to benefit. For all analyses, a two-sided p-value <0.05 will be considered significant.

Based on the small available number of published studies, we anticipate the mean peak serum creatinine level will be 140 umol/L with an expected standard deviation of approximately 30 umol/L. To detect a 10% decrease in mean peak creatinine with 80% power and an alpha of 0.05, we will need a sample size of at least 144 patients. Therefore, the recruitment of 200 patients will be targeted to ensure the study is adequately powered, accounting for patient attrition.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/06/2021

Actual

1/04/2021

Date of last participant enrolment

Anticipated

1/08/2021

Actual

27/06/2021

Date of last data collection

Anticipated

1/11/2021

Actual

27/07/2021

Sample size

Target

200

Accrual to date

Final

160

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment postcode(s) [1]

3084 - Heidelberg

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Austin Health Anaesthesia and Intensive Care Special Purpose Fund

Address [1]

145 Studley Road, Heidelberg, 3084, VIC

Country [1]

Australia

Primary sponsor type

Hospital

Name

Austin Health

Address

145 Studley Road, Heidelberg, 3084, VIC

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Rinaldo Bellomo

Address [1]

Austin Health, 145 Studley Road, Heidelberg, 3084, VIC

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health

Ethics committee address [1]

145 Studley Road, Heidelberg, 3084, VIC

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

26/10/2020

Approval date [1]

11/01/2021

Ethics approval number [1]

Summary

Brief summary

Angiotensin II is an endogenous peptide that causes potent vasoconstriction and promotes the release of aldosterone from the zona granulosa of the adrenal gland. The ATHOS-3 study demonstrated that continuous infusion of angiotensin II could effectively augment mean arterial pressure compared to placebo in patients with catecholamine refractory shock. Secondary analyses suggested that angiotensin II may be of particular benefit in patients with acute kidney injury, especially in those with a high ratio of angiotensin I to II. 

This prospective study will examine the renal outcomes of critically ill patients with distributive shock who receive angiotensin II compared to noradrenaline. Patients who meet all of the inclusion criteria and none of the exclusion criteria will receive a continuous intravenous infusion of angiotensin II until resolution of their distributive shock. The renal outcomes and survival of patients receiving angiotensin II will be compared to those of control patients who received noradrenaline in the preceding period.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Emily See

Address

Austin Health, 145 Studley Road, Heidelberg, 3084, VIC

Country

Australia

Phone

+61 3 9496 5992

Fax

[email protected]

Contact person for public queries

Name

Emily See

Address

Austin Health, 145 Studley Road, Heidelberg, 3084, VIC

Country

Australia

Phone

+61 3 9496 5992

Fax

[email protected]

Contact person for scientific queries

Name

Emily J See

Address

Austin Health, 145 Studley Road, Heidelberg, 3084, VIC

Country

Australia

Phone

+61 3 9496 5992

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Ethics approval not sought for sharing of patient data

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
10139	Ethical approval					381125-(Uploaded-27-01-2021-12-45-35)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	A pilot study of angiotensin ii as primary vasopressor in critically ill adults with vasodilatory hypotension: The aramis study.	2023	https://dx.doi.org/10.1097/SHK.0000000000002109
Embase	Exploring the norepinephrine to angiotensin II conversion ratio in patients with vasodilatory hypotension: A post-hoc analysis of the ARAMIS trial.	2024	https://dx.doi.org/10.1016/j.jcrc.2023.154453

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically