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Trial registered on ANZCTR


Registration number
ACTRN12619000116123p
Ethics application status
Not yet submitted
Date submitted
30/12/2018
Date registered
25/01/2019
Date last updated
25/01/2019
Date data sharing statement initially provided
25/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial of the impact on length of hospital stay of Goal-directed Ultrasound Informed Decision-making for Elderly patients undergoing emergency noncardiac surgery - The ECHOGUIDE III trial
Scientific title
A randomised controlled trial of the impact on length of hospital stay of Goal-directed Ultrasound Informed Decision-making for Elderly patients undergoing emergency noncardiac surgery - The ECHOGUIDE III trial
Secondary ID [1] 296954 0
None
Universal Trial Number (UTN)
Trial acronym
ECHOGUIDE III trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients aged over 65 years admitted to hospital for emergency non-cardiac major surgery (thoracic, arterial vascular, general including colorectal and hepatobiliary, ear nose throat, faciomaxillary, neurosurgery and major orthopaedic surgery). 310916 0
Condition category
Condition code
Surgery 309579 309579 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In addition to standard clinical preoperative evaluation by the treating medical team, participants randomised to the Goal focused ultrasound (GFU) group will receive

i) a preoperative focused cardiac ultrasound performed prior to surgery, following The University of Melbourne iHeartScan protocol
ii) A preoperative lung ultrasound following the The University of Melbourne iLungScan protocol
iii) A preoperative femoral and popliteal vein ultrasound using a two-point compression method

The clinician who performs the GFU will be qualified to the equivalent of a University Graduate Certificate in Clinical Ultrasound and be trained in the iHeartScan and iLungScan protocol and in deep venous ultrasound. In line with a pragmatic trial, any qualified member of the treating team may perform the GFU, and they will complete a structured research report and report those findings to other team members. The information will be available to all members of the treating team before and after surgery, including surgeons, anaesthetists, intensivists, internal medicine physicians, ortho-geriatricians, and emergency medicine physicians (if the GFU is performed in the emergency department).
Intervention code [1] 313228 0
Early detection / Screening
Comparator / control treatment
Participants in the control group will receive standard preoperative evaluation by treating teams in accordance with current standards of care for participating institutions. The control group will represent the standard of care in each participating hospital. Preoperative ultrasound is not precluded in the control group and may be requested by the treating medical team. This does not exclude the patient from the study and the patient will remain in the allocated (control) group in an intention to treat basis.
Control group
Active

Outcomes
Primary outcome [1] 318534 0
Hospital length of stay
Assessed by Business intelligence unit staff, Royal Melbourne Hospital, by standard assessment method used for hospital coding (funding). The hospital length of stay is the time from medical admission to hospital (not emergency department admission) to time when the patient physically leaves their hospital ward bed.
Timepoint [1] 318534 0
Discharge from hospital from the initial admission for the primary surgery.
Secondary outcome [1] 365298 0
Collapsed composite outcome at 30 days after surgery:
i. Mortality – death from any cause.
ii. Myocardial Injury in Noncardiac Surgery (MINS) - The prognostically important thresholds for troponin elevation are: a) 20 ng/L and an increase of at least 5 ng/L from the preoperative value; or, b) greater than or equal to 65 ng/L independent of baseline value. hsTnT plasma levels will be collected before surgery as a baseline and then daily for two days.
iii. Acute kidney injury – RIFLE 1 or greater (serum creatinine (Cr) 1.5–1.9 times baseline value within 7 days, or greater than or equal to 27mmol.L-1 (0.3mg/ dL) increase within 48 h or Urine output less than or equal to 0.5 mL/kg/h for 6–12 h)
iv. Pulmonary Embolus – A new blood clot or thrombus within the pulmonary arterial system, confirmed on computed tomography, or cardiac ultrasound, or autopsy.
v. Congestive cardiac failure - The diagnosis required both clinical (i.e., any of the following signs: raised jugular venous pressure, respiratory rales, crepitations, or presence of S3) and radiographic evidence (eg. vascular redistribution, interstitial pulmonary oedema, or frank alveolar pulmonary oedema)
vi. Hospital readmission – any cause. This will be assessed from hospital records.
Timepoint [1] 365298 0
30 days and 1 year after surgery
Secondary outcome [2] 365299 0
Postoperative Quality of Recovery measured using the Postoperative Quality of Recovery Scale (PostopQRS). This scale has been used in multiple studies at the RMH and is a patient reported outcome measurement that determines quality of recovery in a multidimensional manner over multiple time periods. It will be conducted prior to surgery (Baseline) and repeated on Days 1, 3, 7, 30 and at 12 months after surgery. Following hospital discharge, the survey is conducted via the telephone.
Timepoint [2] 365299 0
Days 1, 3, 7, 30 and at 12 months after surgery
Secondary outcome [3] 365300 0
Additional costs of routine FCU will be balanced against other costs due to changes in duration of hospital stay, type of ward, and medical resource consumption due to improved survival. Consent will be sought to obtain total costs of care in each group over the study period. Healthcare resource consumption in each group, including hospitalisations, general practice and specialist consultations, investigations and medications will be obtained. Units of healthcare resources consumed will be combined with Australian unit costs derived from the PBS, Medicare and A-DRGs. Additional costs of the intervention will be accounted for. Additionally, health utility, a summary measure of quality of life, will be measured using the EQ-5D-5L. The EQ5D5L will be administered in written form (takes <1 minute to complete) at baseline as part of the preoperative patient assessment, and at 30 days and 12 months as part of the patient follow-up assessment. Health utility differences between each group, combined with survival differences, will allow calculation of quality-adjusted life expectancy, and thus incremental costs per quality-adjusted life years (QALYs) gained. Changes in QALYs will be balanced against differences in total costs for each group, enabling assessment of the incremental cost- effectiveness of the intervention versus current standard of care for the study period.
Timepoint [3] 365300 0
30 days and 1 year after surgery
Secondary outcome [4] 365301 0
Changes to the preoperative diagnosis and or management plan by the anaesthetist.
This is a composite secondary outcome. It is a positive outcome if:
i) the diagnosis is changed by the ultrasound
ii) the management is changed by the ultrasound
iii) the diagnosis and management is changed by the ultrasound
The data is collected by:
1. The treating aanaesthetist completes their standard preoperative assessment and then completes a structured research form of their planned diagnosis and management
2. The ultrasound results are given to the anaesthetist
3. The anaesthetist is asked to repeat their diagnosis and management plan
Any difference between the before and after ultrasound diagnosis and management plans are recorded as changes due to the ultrasound
Timepoint [4] 365301 0
On the day of surgery

Eligibility
Key inclusion criteria
• Age >65 years and admitted to hospital
• Scheduled for emergency surgery
• Expected surgical duration >1 hour
• Surgery type: thoracic, arterial vascular, general including colorectal and hepatobillary, ear nose throat, faciomaxillary, neurosurgery and major orthopaedic surgery
• Requiring overnight hospital stay
Minimum age
66 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Requiring surgical fixation of neck of femur (this has already been reported)
• Admitted for social rather than medical reasons
• Unable to obtain consent from patient or responsible person
• The patient has received a transthoracic echocardiogram or CT chest during the admission and prior to enrollment.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The allocation sequence will be concealed by the web-based enrolment system. The site research staff will recruit patients, reveal allocation and organise a qualified practitioner to perform the FCU before surgery. As the inclusion of the FCU in the clinical records is essential for all members of the treating team to access it, and in accordance with a pragmatic trial, the research staff who will collect outcome data cannot be blinded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation is performed using internet software (https://www.sealedenvelope.com/simple-randomiser/v1/lists) in unequal block sizes of 2, 4 and 6.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size estimates and statistical methods has been written by our consulting statistician, Dr Sandy Clarke, from the University of Melbourne Statistical Centre.

SAMPLE SIZE CALCULATION
Hospital length of stay (LOS) is expected to be skewed and hence will be log transformed for the purposes of analysis. Control data (Group PS, Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839-47.) suggest we can expect a mean of around 0.9, and a standard deviation of 0.4 on the log10 scale. The primary outcome will be tested using a 2-sample t-test on the log-transformed LOS data. If any participants are still in hospital at the completion of the trial, these data will be analysed using the Mantel-Cox logrank test. Based on the t-test, in order to detect a clinically important reduction in LOS of 25% (equivalent to a change of 0.13 on the log scale) with power of 0.8 and size 0.05, 162 participants are required in each of the two treatment groups, which will be rounded up to a total of 350 participants to allow for attrition and/or censoring.

STATISTICAL ANALYSIS
Primary outcome
Data will be analysed on an intention to treat basis. The primary outcome will be analysed using a 2-sample t-test on the log-transformed length of stay data. If any participants are still in hospital at the completion of the trial, these data will be analysed using the Mantel-Cox logrank test. P<0.05 will define significance.

Secondary outcomes
For secondary endpoints, significance will be defined as p<0.01 to reduce the risk of Type 1 error.

i) The collapsed composite outcome will be compared between GFU and control groups using a distinct effects generalised estimating equation model, specifically, an average relative effect test to determine the common treatment effect across the six components. The heterogeneity of the treatment effects across components will be formally assessed with a treatment by component interaction test in the GEE. This approach better considers the different frequencies of each component, and reduces the risk of a single component dominating the collapsed composite outcome. All six component outcomes will be compared between the two groups, with methodology depending on outcome type. The same GEE model used for the 30-day collapsed composite will be repeated at one year. Kaplan Meier survival analysis will be used for the time to event data and comparison of proportions will be used for event data. Subgroup analyses will assess the treatment-by-subgroup interaction within the GEE model framework for the following three factors, which are considered as important contributors to heterogeneity of treatment effect: 1) Age 65-75 versus age >75 years; 2) Presence of cardiac symptoms versus asymptomatic; 3) Living at home versus aged care facility.

ii) The health economic analysis will be performed by health economists. Additional costs of routine FCU will be balanced against other costs due to changes in duration of hospital stay, type of ward, and medical resource consumption due to improved survival. Consent will be sought to obtain total costs of care in each group over the study period. Healthcare resource consumption in each group, including hospitalisations, general practice and specialist consultations, investigations and medications will be obtained. Explicit written individual patient consent to access the PBS and hospital records will be obtained as part of the clinical trial consent process. Units of healthcare resources consumed will be combined with Australian unit costs derived from the PBS, Medicare and A-DRGs. Additional costs of the intervention will be accounted for. Additionally, health utility, a summary measure of quality of life, will be measured using the EQ-5D-5L, a standard, internationally validated instrument with Australian population norms. The EQ5D5L will be administered in written form (takes <1 minute to complete) at baseline as part of the preoperative patient assessment, and at 30 days and 12 months as part of the patient follow-up assessment. Health utility differences between each group, combined with survival differences, will allow calculation of quality-adjusted life expectancy, and thus incremental costs per quality-adjusted life years (QALYs) gained. It is hypothesised the additional costs of intervention will be partially or fully offset by reductions in the cost of hospitalisation. Changes in QALYs will be balanced against differences in total costs for each group, enabling assessment of the incremental cost- effectiveness of the intervention versus current standard of care for the study period. In addition, a Markov simulation model will be developed using TreeAge Decision Analysis software (Inc, Williamstown, Massachusetts) to project trial results to patient lifetimes. Univariate sensitivity analysis will be performed to identify parameters with the greatest impact on projected costs and clinical outcomes. Probabilistic sensitivity analysis, involving simultaneous sampling for distributions of key parameters, will be used to account for uncertainty in multiple parameters.

iii) Changes in diagnosis and management by the anaesthetist are described as frequency data without statistical comparisons.

iv) Quality of Recovery will be assessed as the incidence of recovery in each group over time using a Generalised Linear Mixed Model (GLMM) method.

Data is coded and stored in Microsoft Excel 2010 and analysed using SPSS V21 (SPSS Inc., Chicago, IL, USA).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12806 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 25278 0
3050 - Parkville
Recruitment outside Australia
Country [1] 21151 0
South Africa
State/province [1] 21151 0
Cape Town

Funding & Sponsors
Funding source category [1] 301523 0
University
Name [1] 301523 0
University of Melbourne
Address [1] 301523 0
Department of Surgery
Level 6 Centre for Medical Research
University of Melbourne
Royal Parade
Parkville
VIC 3050
Country [1] 301523 0
Australia
Primary sponsor type
Hospital
Name
Royal Melbourne Hospital
Address
300 Grattan Street
Parkville
VIC 3050
Country
Australia
Secondary sponsor category [1] 301225 0
University
Name [1] 301225 0
University of Melbourne
Address [1] 301225 0
Department of Surgery
Level 6 Centre for Medical Research
University of Melbourne
Royal Parade
Parkville
VIC 3050
Country [1] 301225 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 302265 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 302265 0
Royal Melbourne Hospital
300 Grattan Street
Parkville
VIC 3050
Ethics committee country [1] 302265 0
Australia
Date submitted for ethics approval [1] 302265 0
31/01/2019
Approval date [1] 302265 0
Ethics approval number [1] 302265 0

Summary
Brief summary
Emergency surgery is a growing health issue because it is becoming more common and the patients are becoming older and sicker. One month after surgery, one in twenty patients do not survive and one in five patients suffer a major medical issue. One of reasons for this poor outcome is that there is often not enough time for doctor’s to fully evaluate patient’s medical status before emergency surgery. Therefore, the surgery often proceeds without the doctors having a complete medical evaluation of the patient. This can result in errors in treatment and a delay in correct diagnosis, that can result in progression of the disease or harmful treatments.

A brief ultrasound examination of the patient has been shown to improve doctor’s medical evaluation of patients before surgery. For example, an ultrasound of the heart may identify a weak heart or blocked valve. In this study we wish to find out whether an ultrasound of the heart, lungs and leg veins results in a better medical outcome and shorter length of hospital stay in patients over 65 years old requiring emergency surgery.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89626 0
A/Prof David Canty
Address 89626 0
Department of Surgery
Level 6 Centre for Medical Research
University of Melbourne
Royal Parade
Parkville
VIC 3050
Country 89626 0
Australia
Phone 89626 0
+61 429058878
Fax 89626 0
Email 89626 0
dcanty@unimelb.edu.au
Contact person for public queries
Name 89627 0
A/Prof David Canty
Address 89627 0
Department of Surgery
Level 6 Centre for Medical Research
University of Melbourne
Royal Parade
Parkville
VIC 3050
Country 89627 0
Australia
Phone 89627 0
+61 429058878
Fax 89627 0
Email 89627 0
dcanty@unimelb.edu.au
Contact person for scientific queries
Name 89628 0
A/Prof David Canty
Address 89628 0
Department of Surgery
Level 6 Centre for Medical Research
University of Melbourne
Royal Parade
Parkville
VIC 3050
Country 89628 0
Australia
Phone 89628 0
+61 429058878
Fax 89628 0
Email 89628 0
dcanty@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Need to consult research team
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 911 0
Study protocol
Citation [1] 911 0
Link [1] 911 0
Email [1] 911 0
Other [1] 911 0
Summary results
No Results