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Trial registered on ANZCTR


Registration number
ACTRN12619001668190
Ethics application status
Approved
Date submitted
12/09/2019
Date registered
28/11/2019
Date last updated
25/06/2021
Date data sharing statement initially provided
28/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
RELIEF II Pilot: Low-dose Noradrenaline in Major Surgery
Scientific title
RELIEF II Pilot: A Safety and Feasibility Trial of a Low-dose Noradrenaline Infusion in Major Surgery
Secondary ID [1] 299269 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Blood Pressure during and after surgery 314404 0
Condition category
Condition code
Anaesthesiology 312738 312738 0 0
Anaesthetics
Cardiovascular 313011 313011 0 0
Normal development and function of the cardiovascular system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Low-dose intravenous continuous noradrenaline infusion (10mcg/ml) in patients undergoing major surgery, titrated to a target systolic BP (120mmHg or within 10% of the patient’s lowest preoperative systolic BP value, whichever is lower) with a maximum rate of 0.1mcg/kg/min. The study drug infusion will commence on induction and continue for up to 4 hours postoperatively for patients going to the ward via PACU, and up to 24 hours postoperatively for patients being admitted to HDU/ICU.
Intervention code [1] 315554 0
Treatment: Drugs
Comparator / control treatment
Normal saline solution
Control group
Placebo

Outcomes
Primary outcome [1] 321376 0
1. Feasibility endpoints, as defined by:
- Number of eligible patients per week at each centre
- Consent rate
Timepoint [1] 321376 0
Number of eligible patients per week at each centre: Total number of patients consented and randomised to receive study treatment, per week, for each site

Consent rate: Number of patients who are approached for consent and choose to participate (and are eligible), divided by the total number of patients who are approached for consent
Primary outcome [2] 321836 0
- Successful study drug administration
Timepoint [2] 321836 0
Proportion of patients who have completed the study and without interruption (not according to protocol) of the study drug infusion intraoperatively. If the study drug infusion is interrupted for greater than 5 minutes (not according to protocol), or the infusion is discontinued prior to the end of surgery, reasons for these occurrences will be recorded.
Primary outcome [3] 321837 0
- Inadvertent unblinding
Timepoint [3] 321837 0
At the end of the case, the anaesthesiologist will be asked which group they think their patient has been allocated to: Noradrenaline, placebo, or uncertain.
Secondary outcome [1] 374819 0
2. Efficacy endpoints, as defined by:
- Mean and systolic BP during and after surgery until cessation of study drug infusion
Timepoint [1] 374819 0
BP measurements Intraoperatively and postoperatively until cessation of study drug infusion, via invasive arterial line: Highest SBP (persisting > 5 minutes), lowest SBP (persisting > 5 minutes), average SBP (mmHg), maximum MAP (persisting > 5 minutes), minimum MAP (persisting > 5 minutes), average MAP (mmHg)
Secondary outcome [2] 376416 0
- Study drug average and peak infusion rate, duration and total volume
Timepoint [2] 376416 0
Intraoperative average study drug infusion rate (ml/min), minimum infusion rate (ml/min), maximum infusion rate (ml/min), total volume of intraoperative infusion delivered (ml), total duration of intraoperative and postoperative study drug infusion (minutes)
Secondary outcome [3] 376417 0
- Adjunctive vasopressor or inotrope therapy
Timepoint [3] 376417 0
Intraoperative and postoperative record of any additional vasopressor or inotropes administered, including total dosages, until cessation of the study drug (up to 4 hours post-op for PACU, 24 hours for HDU/ICU admission).
Secondary outcome [4] 376418 0
- Total intraoperative IV fluid volume
Timepoint [4] 376418 0
Total volume of intraoperative fluid administration (ml), as documented by the anaesthesiologist administering the fluid.
Secondary outcome [5] 376419 0
- Intraoperative urine output
Timepoint [5] 376419 0
Intraoperative total urinary volume (ml) measured via In-dwelling catheter (IDC), excluding first bladder urinary volume
Secondary outcome [6] 376420 0
- Postoperative renal function, as measured by delta-creatinine
Timepoint [6] 376420 0
Difference between preoperative creatinine and highest postoperative creatinine value within 48 hours (mmol/L) and also at discharge, as measured by pathology blood results.
Secondary outcome [7] 376426 0
3. Safety endpoints, as defined by:
- Local and systemic complications from study drug administration
Timepoint [7] 376426 0
Intraoperative and postoperative side effects will be monitored:
Local - in the absence of a central line, the skin surrounding the peripheral cannula used for study drug administration will be assessed postoperatively on days 0, 1, and 2 or 3 for skin injury, using a scoring system 0-4, where 0 is none, 1 is minor, 2 is moderate, 3 is moderately severe and 4 is severe or evidence of skin necrosis.
Systemic - haemodynamic, including severe tachyarrhythmias, bradycardia, hypotension or hypertension, and metabolic, including severe derangements of blood sugar or lactate
Secondary outcome [8] 376427 0
- Any drug errors including other drugs being administered via the dedicated arm of the TIVA 3 way giving set through which the study drug is being administered
Timepoint [8] 376427 0
The anaesthesiologist will document whether any other drug was administered through the dedicated arm of the TIVA 3 way giving set
Secondary outcome [9] 376429 0
- Drop-out rate and reason for drop-out
Timepoint [9] 376429 0
If the study drug infusion is ceased prior to the end of surgery or target completion time postoperatively (4 hours for PACU, 24 hours for HDU/ICU admission), this event will be recorded, including the time the study drug was ceased, and the associated reasons

Eligibility
Key inclusion criteria
Adults requiring general anaesthesia for non-cardiac elective surgery, of at least 2 hour duration, and expected hospital stay of at least three days. In addition, patients should be at increased risk of postoperative complications, such as increased age, ASA score 3-4, history of cardiac disease, or extremes of weight.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patient refusal, preoperative vasopressor or isotrope revirement, videoscopic surgery with an incision less than 10cm, use of monoamine oxidase inhibitors, pregnant or breastfeeding women.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random assignment from a computer-generated list
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
60 patients chosen as a sample size to provide sufficient information to guide the design of a future definitive clinical trial.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
2/12/2019
Actual
12/12/2019
Date of last participant enrolment
Anticipated
30/04/2020
Actual
24/10/2020
Date of last data collection
Anticipated
Actual
25/10/2020
Sample size
Target
60
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14772 0
The Alfred - Melbourne
Recruitment hospital [2] 14773 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 28004 0
3004 - Melbourne
Recruitment postcode(s) [2] 28005 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 303801 0
Self funded/Unfunded
Name [1] 303801 0
Country [1] 303801 0
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Rd, Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 303923 0
None
Name [1] 303923 0
N/A
Address [1] 303923 0
N/A
Country [1] 303923 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304320 0
HREC, Alfred Health
Ethics committee address [1] 304320 0
Ethics committee country [1] 304320 0
Australia
Date submitted for ethics approval [1] 304320 0
23/09/2019
Approval date [1] 304320 0
10/12/2019
Ethics approval number [1] 304320 0

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

Contacts
Principal investigator
Name 96526 0
Prof Paul Myles
Address 96526 0
Alfred Health, 55 Commercial Rd, Melbourne VIC 3004
Country 96526 0
Australia
Phone 96526 0
+61 03 9076 3176
Fax 96526 0
Email 96526 0
p.myles@alfred.org.au
Contact person for public queries
Name 96527 0
Sophie Wallace
Address 96527 0
Alfred Health, 55 Commercial Rd, Melbourne VIC 3004
Country 96527 0
Australia
Phone 96527 0
+61 03 9076 2651
Fax 96527 0
Email 96527 0
s.wallace@alfred.org.au
Contact person for scientific queries
Name 96528 0
Paul Myles
Address 96528 0
Alfred Health, 55 Commercial Rd, Melbourne VIC 3004
Country 96528 0
Australia
Phone 96528 0
+61 03 9076 3176
Fax 96528 0
Email 96528 0
p.myles@alfred.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseLow-Concentration Norepinephrine Infusion for Major Surgery: A Safety and Feasibility Pilot Randomized Controlled Trial.2022https://dx.doi.org/10.1213/ANE.0000000000005811
N.B. These documents automatically identified may not have been verified by the study sponsor.