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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] 303038 0
None
Universal Trial Number (UTN)
Trial acronym
ARAMIS-ICU
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Distributive shock
 320107 0
Condition category
Condition code
Renal and Urogenital 318045 318045 0 0
Kidney disease
Cardiovascular 318345 318345 0 0
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] 319325 0
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] 326097 0
Peak serum creatinine (umol/L)
Timepoint [1] 326097 0
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] 390112 0
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] 390112 0
7 days post-commencement of infusion
Secondary outcome [2] 390113 0
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] 390113 0
7 days post-commencement of infusion
Secondary outcome [3] 390114 0
Average daily urine output (L/day) as assessed using the patient medical record
Timepoint [3] 390114 0
Daily for 7 days post-commencement of infusion
Secondary outcome [4] 390115 0
Cumulative fluid balance (L) as assessed using the patient medical record
Timepoint [4] 390115 0
7 days post-commencement of infusion
Secondary outcome [5] 390116 0
Lowest mean arterial pressure as assessed using an arterial line
Timepoint [5] 390116 0
Assessed at baseline and hourly until the cessation of the infusion or for a maximum of 7 days
Secondary outcome [6] 390117 0
The number of patients who require invasive ventilation following initiation of intervention or control infusions as assessed using the patient medical record
Timepoint [6] 390117 0
7 days post-commencement of infusion
Secondary outcome [7] 390118 0
ICU length of stay as assessed using the patient medical record
Timepoint [7] 390118 0
Patient discharge from ICU
Secondary outcome [8] 390119 0
Hospital length of stay as assessed using the patient medical record
Timepoint [8] 390119 0
Patient discharge from hospital
Secondary outcome [9] 390120 0
Days alive and free of renal replacement therapy (composite) as assessed using the patient medical record
Timepoint [9] 390120 0
28 days post-commencement of infusion
Secondary outcome [10] 390121 0
The number of patients who die during their ICU stay as assessed using the patient medical record
Timepoint [10] 390121 0
ICU discharge
Secondary outcome [11] 391025 0
The number of patients who die in hospital as assessed using the patient medical record
Timepoint [11] 391025 0
Hospital discharge
Secondary outcome [12] 391026 0
The number of patients who die within 28 days of initiation of the infusion as assessed using the patient medical record
Timepoint [12] 391026 0
28 days post-commencement of infusion
Secondary outcome [13] 391027 0
The number of patients who develop a thromboembolic event (DVT, PE, elevated troponin) as assessed using the patient medical record
Timepoint [13] 391027 0
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?
No
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] 18266 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 32335 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 307451 0
Hospital
Name [1] 307451 0
Austin Health Anaesthesia and Intensive Care Special Purpose Fund
Country [1] 307451 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
145 Studley Road, Heidelberg, 3084, VIC
Country
Australia
Secondary sponsor category [1] 308124 0
Individual
Name [1] 308124 0
Rinaldo Bellomo
Address [1] 308124 0
Austin Health, 145 Studley Road, Heidelberg, 3084, VIC
Country [1] 308124 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307529 0
Austin Health
Ethics committee address [1] 307529 0
Ethics committee country [1] 307529 0
Australia
Date submitted for ethics approval [1] 307529 0
26/10/2020
Approval date [1] 307529 0
11/01/2021
Ethics approval number [1] 307529 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107558 0
Dr Emily See
Address 107558 0
Austin Health, 145 Studley Road, Heidelberg, 3084, VIC
Country 107558 0
Australia
Phone 107558 0
+61 3 9496 5992
Fax 107558 0
Email 107558 0
[email protected]
Contact person for public queries
Name 107559 0
Emily See
Address 107559 0
Austin Health, 145 Studley Road, Heidelberg, 3084, VIC
Country 107559 0
Australia
Phone 107559 0
+61 3 9496 5992
Fax 107559 0
Email 107559 0
[email protected]
Contact person for scientific queries
Name 107560 0
Emily J See
Address 107560 0
Austin Health, 145 Studley Road, Heidelberg, 3084, VIC
Country 107560 0
Australia
Phone 107560 0
+61 3 9496 5992
Fax 107560 0
Email 107560 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ethics approval not sought for sharing of patient data


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10139Ethical 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
SourceTitleYear of PublicationDOI
EmbaseA pilot study of angiotensin ii as primary vasopressor in critically ill adults with vasodilatory hypotension: The aramis study.2023https://dx.doi.org/10.1097/SHK.0000000000002109
EmbaseExploring the norepinephrine to angiotensin II conversion ratio in patients with vasodilatory hypotension: A post-hoc analysis of the ARAMIS trial.2024https://dx.doi.org/10.1016/j.jcrc.2023.154453
N.B. These documents automatically identified may not have been verified by the study sponsor.