Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001320246
Ethics application status
Approved
Date submitted
29/06/2018
Date registered
6/08/2018
Date last updated
9/06/2021
Date data sharing statement initially provided
20/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of indicators of heart and circulation injury in adult patients undergoing major abdominal surgery.
Scientific title
OPtimisation of Perioperative Cardiovascular Management to Improve Surgical outcomE II trial (Optimise II) - biomarker sub-study for Australian sites
Secondary ID [1] 295326 0
none
Universal Trial Number (UTN)
Universal Trial Number (UTN) is U1111-1216-4595
Trial acronym
Linked study record
This is a substudy of the OPTIMISE II trial. ISRCTN 39653756

Health condition
Health condition(s) or problem(s) studied:
Postoperative infection 308525 0
Gastrointestinal surgery 308593 0
Postoperative complications 308594 0
Condition category
Condition code
Anaesthesiology 307544 307544 0 0
Anaesthetics
Surgery 307545 307545 0 0
Other surgery
Cardiovascular 307546 307546 0 0
Other cardiovascular diseases
Infection 307621 307621 0 0
Other infectious diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The OPtimisation of Perioperative Cardiovascular Management to Improve Surgical outcomE II trial (Optimise II) is large multi-centre randomised trial, which seeks to establish whether targeted fluid optimisation with minimally invasive cardiac output monitoring and a low dose inotrope infusion can improve outcomes in patients having elective gastrointestinal surgery.

In the intervention group of OPTIMISE II, a haemodynamic protocol will start at the induction of surgery and continue until 4 hours after surgery. Cardiac output and stroke volume will be measured by cardiac output monitor, Edwards Lifesciences Flotrac(TM) or Clearsight (TM). In addition to the maintenance fluid and blood products, patients will receive 250ml fluid challenges with a recommended solution as required in order to achieve a maximal value of stroke volume. The absence of fluid responsiveness will be defined as the absence of a sustained rise in stroke volume of at least 10% for 20 minutes or more. In addition, patients will receive a low dose inotrope infusion at a fixed rate which will be commenced after fluid replacement has been initiated. The choice of inotrope will be made at the discretion of the local investigator, according to local preference and availability. The options are dobutamine at a dose/rate of 2.5 µg/kg/min and dopexamine at an equipotent dose/rate of 0.5 µg/kg/min.

In this sub-study, we will collect biomarkers in order to identify any differences in cardiac injury (Troponin) and endothelial injury between the two comparator groups in Optimise II, cardiac output-guided haemodynamic therapy with an inotrope versus "usual care" without the use of cardiac output monitoring.

The biomarkers will be collected over 48hrs from the beginning of surgery until day 2 post surgery.
Intervention code [1] 301689 0
Diagnosis / Prognosis
Comparator / control treatment
The comparator/control group in the OPTIMISE II trial will be managed by clinical staff according to usual practice, "usual care". This will include 250ml fluid challenges with a recommended intra-venous fluid administered at the discretion of the clinician guided by pulse rate, arterial pressure, urine output, core-peripheral temperature gradient, serum lactate and base excess. Patients should not be planned to have cardiac output monitoring.
Control group
Active

Outcomes
Primary outcome [1] 306522 0
Syndecan-1 levels between the two groups, usual care vs. GDT, will be compared and analyzed for a significant difference. Syndecan-1 levels will be assayed from serum blood samples.
Timepoint [1] 306522 0
0 hours (baseline before surgery) , 6 hours after surgery, 1 day after surgery (primary endpoint) and 2 days after surgery.
Primary outcome [2] 306523 0
Troponin levels between the two groups, usual care vs. GDT, will be measured by serum assay and analyzed for a significant difference.
Timepoint [2] 306523 0
0 hours (baseline before surgery) , 6 hours after surgery, 1 day after surgery (primary endpoint) and 2 days after surgery.
Secondary outcome [1] 348985 0
Additional exploratory biomarkers of endothelial dysfunction may be explored. They will use the same serum sample collected at the same timepoints as the biomarkers specified in the primary outcome.
Timepoint [1] 348985 0
0 hours (baseline before surgery) , 6 hours after surgery, 1 day after surgery and 2 days after surgery.

Eligibility
Key inclusion criteria
Patients who have consented and recruited to the OptimiseII trial which includes
patients aged 65 years and over undergoing major elective surgery involving the gastrointestinal tract that is expected to take longer than 90 minutes.
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Inability or refusal to provide patient consent
• clinician refusal (including intention to monitor cardiac output from the start of surgery regardless of study group allocation)
• American Society of Anesthesiologists (ASA) score of I
• patients expected to die within 30 days
• acute myocardial ischaemia within 30 days prior to randomisation
• acute pulmonary oedema within 30 days prior to randomisation
• contra-indication to low-dose inotropic medication
• pregnancy at time of enrolment
• current participation in another clinical trial of a treatment with a similar biological mechanism or primary outcome measure

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
1. Syndecan-1 levels between the two groups, usual care vs. GDT, will be compared and analyzed for a significant difference.
2. Troponin levels between the two groups, usual care vs. GDT, will be compared and analyzed for a significant difference.
3. Logistic regression modelling for the primary outcome will be used to explore associations with biomarkers.
4. Secondary outcomes such as renal injury or cardiovascular events may also be explored for association with biomarkers

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/08/2018
Actual
11/01/2019
Date of last participant enrolment
Anticipated
31/12/2021
Actual
Date of last data collection
Anticipated
30/06/2022
Actual
Sample size
Target
200
Accrual to date
60
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 11273 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 11274 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 11275 0
The Alfred - Prahran
Recruitment postcode(s) [1] 23155 0
3065 - Fitzroy
Recruitment postcode(s) [2] 23156 0
3084 - Heidelberg
Recruitment postcode(s) [3] 23157 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 299916 0
Charities/Societies/Foundations
Name [1] 299916 0
Australian and New Zealand College of Anaesthetists
Country [1] 299916 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Melbourne
Address
41 Victoria Parade, Fitzroy, Victoria 3065, Australia
Country
Australia
Secondary sponsor category [1] 299283 0
None
Name [1] 299283 0
Address [1] 299283 0
Country [1] 299283 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300785 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 300785 0
41 Victoria Pde, Fitzroy, Vic 3065 Australia
Ethics committee country [1] 300785 0
Australia
Date submitted for ethics approval [1] 300785 0
Approval date [1] 300785 0
20/07/2017
Ethics approval number [1] 300785 0

Summary
Brief summary
The OPtimisation of Perioperative Cardiovascular Management to Improve Surgical outcomE II trial (Optimise II) is a large multi-centre randomised trial, which seeks to establish whether increasing blood flow from the heart during major abdominal surgery reduces the risk of infection. Within this large study, blood samples from 200 patients will be collected. All samples will be analysed for evidence of heart injury and 50 samples will be analysed also for circulation injury. This blood sample analysis will try to identify patients who are at higher risk of complications after surgery.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2844 2844 0 0
/AnzctrAttachments/375438-Optimise II AUS Biomarker protocol amend.pdf

Contacts
Principal investigator
Name 84810 0
Dr Tuong Phan
Address 84810 0
St Vincent's Hospital Melbourne,
41 Victoria Pde, Fitzroy, Vic 3065, Australia
Country 84810 0
Australia
Phone 84810 0
+61392314253
Fax 84810 0
Email 84810 0
[email protected]
Contact person for public queries
Name 84811 0
Dr Tuong Phan
Address 84811 0
St Vincent's Hospital Melbourne,
41 Victoria Pde, Fitzroy, Vic 3065, Australia
Country 84811 0
Australia
Phone 84811 0
+61392314253
Fax 84811 0
Email 84811 0
[email protected]
Contact person for scientific queries
Name 84812 0
Dr Tuong Phan
Address 84812 0
St Vincent's Hospital Melbourne,
41 Victoria Pde, Fitzroy, Vic 3065, Australia
Country 84812 0
Australia
Phone 84812 0
+61392314253
Fax 84812 0
Email 84812 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
Consent for publicly available data was not explicitly obtained; as a result, the data will not be made available.

There is also no protection against the data being used in a way that infringes on the participants' and the trial investigator's rights to confidentiality and reputation.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
5776Study protocol  [email protected]



Results publications and other study-related documents

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

Documents added automatically
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