Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000812190
Ethics application status
Approved
Date submitted
16/05/2019
Date registered
4/06/2019
Date last updated
4/06/2019
Date data sharing statement initially provided
4/06/2019
Date results information initially provided
4/06/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Preventing thromboembolism after surgery using a patient and procedure specific approach to thromboembolism risk assessment and prevention, in cancer surgery patients.
Scientific title
Surgical Thrombo-Embolism Prevention: Implementation and impact of a risk-stratified thromboprophylaxis model on postoperative thromboembolism in cancer surgery patients
Secondary ID [1] 298304 0
None
Universal Trial Number (UTN)
Trial acronym
STEP-QIP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postoperative thromboembolism 312863 0
Postoperative bleeding 312864 0
Cancer 312934 0
Condition category
Condition code
Blood 311362 311362 0 0
Clotting disorders
Surgery 311363 311363 0 0
Other surgery
Anaesthesiology 311364 311364 0 0
Other anaesthesiology
Cancer 311427 311427 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The multi-staged Surgical Thrombo-Embolism Prevention quality improvement program (STEP-QIP) established a protocol that stratified patients into low, intermediate, and high risk profiles according to surgical procedure and patient baseline medical risk. Expert-endorsed risk-specific thromboprophylaxis strategies were then applied. The Surgical Thrombo-Embolism Prevention protocol (STEP-P) consisted of a risk-assessment tool and decision-making algorithm, based on evidence-based risk-category specific recommendations for thromboprophylaxis (TP) – including type (mechanical-TP, pharmacological-TP), time of initiation, and duration of application of interventions. The risk assessment model defined the risk profile for the specific patient interaction. The initial step assessed the procedural thromboembolism (TE) risk to determine the surgical risk profile - low, intermediate or high – which was then combined with the patient’s medical TE risk profile to generate an overall TE risk profile. The surgical risk profile considered the duration of surgery and the extent of tissue injury. Surgery under 45 minutes was considered as low TE risk and included endoscopic procedures and excisions of cutaneous lesions. Non-major surgery and major surgery equal or greater than 45 minutes was classified as intermediate and high TE risk, respectively. Intermediate TE surgeries included procedures on connective tissue, non-complex orthopaedic, head and neck (e.g. parotidectomy, thyroidectomy), breast, non-complex abdominal (e.g. appendectomy), laparoscopic/robotic partial nephrectomy or simple prostatectomy that did not include pelvic lymph node dissection. High TE surgery included major intracavity (thoracic/abdominal/pelvic), sarcoma, pelvic lymph node dissection, obstetric, microvascular free flap reconstruction, vascular, complex orthopaedic, cardiothoracic/oesophagectomy and cranial/spinal procedures.
The medical risk was simplified to a TE risk score based on 13 validated risk factors. Each risk factor was given a weighted risk score from 0.5 to 2 according to published odds ratio. A score of 2 or more escalated the surgical risk profile from low to intermediate or from intermediate to high. Factors that received a TE risk score of 0.5 included: age greater than 60, body mass index (BMI) between 35 and 40 Kg/m^2, heart failure or recent acute myocardial infarction (within 6 weeks), oestrogen hormone therapy, platelet count > 350 x 10^9/L, and Fibrinogen > 4 g/L. Factors that received a TE risk score of 1 included active cancer (excludes localised non-melanomatous skin lesions), severe obesity BMI > 40 Kg/m^2, prolonged (> 4 days) or severe immobility prior to surgery, and the oral contraceptive pill. Factors that received a TE risk score of 2 included prior Thromboembolism, known inherited thrombophilia, and pregnancy or puerperium.
The surgical and medical risk profiles together determined the overall TE risk classification as low, intermediate or high-risk profiles. Intermediate and high-risk profiles received sequential compression devices (SCDs) (Covidien - Kendal SCD express sleeves, thigh length) for the duration of the surgery (intraoperative SCD). Covidien Kendal SCDs were the compression device standard at our institution and were used during this study. Intermediate risk profiles also received Thromboembolic Deterrent Stockings (TEDs) for at least 7 days. High risk patients received TEDS for the duration of their inpatient stay only. Low risk and intermediate risk patient that required admission after their surgery received P-TP for the duration of their inpatient stay only. For high risk patients P-TP was added, which was started intraoperatively or within six hours postoperatively. P-TP was continued for at least 28 days for patients having major abdominopelvic surgery and at least 7 days for all other major surgery. Procedures meeting inclusion into the major abdominopelvic surgery risk group included colectomies, anterior resection, abdominoperineal resection, pelvic exenteration, major debulking surgery including hyperthermic intraperitoneal chemotherapy (HIPEC), and liver resections. Low and intermediate risk profile patients that were admitted to hospital received P-TP only for the duration of their hospital admission (inpatient P-TP).
The Low Molecular Weight Heparin enoxaparin was used for P-TP, with a dosing regimen of 40 mg for patients between 50 and 120 kg, 20 mg for under 50 kg, and 60 mg for over 120 kg. This was prescribed as a once daily dose, subcutaneously. The dose was halved if the patient’s creatinine clearance was below 30 ml/min. Contraindications to TP were also defined. SCDs were continued postoperatively if a contraindication to P-TP administration existed or if P-TP was prescribed later than 6 hours after completion of surgery. SCD use was ceased once P-TP was re-initiated. All thromboprophylaxis decisions were made by senior clinicians (surgeons and anaesthetists) in theatre. All ongoing thromboprophylaxis orders were charted by the treating anaesthetist prior to leaving the theatre complex. The STEP risk profile was handed over to recovery nursing staff. Nursing staff ensured that mechanical measures were applied prior to leaving the anaesthetic recovery room and that ward orders were completed on the inpatient drug chart. Patient awareness of postoperative TE was improved on the ward through targeted educational brochures and risk assessment questionnaires provided at the time of surgical booking. Daily postoperative rounds were conducted by clinical pharmacists to assess and enhance compliance with STEP-P. Thromboprophylaxis orders were checked against the STEP protocol by clinical pharmacists on the ward and fed back to treating unit staff. Post-discharge TP prescriptions were signed off by clinical pharmacists and prescribed according to the minimal recommended durations. Patients were provided with education with regards to the risk of postoperative TE and self-administration techniques for enoxaparin. Discharge bundles consisting of educational material and sharps disposal bin were also provided. Prospective compliance audits were also conducted.
Intervention code [1] 314503 0
Prevention
Comparator / control treatment
A baseline control group of all surgical admissions receiving standard care prior to implementation of the STEP-QIP. Standard care was described as any thromboprophylaxis intervention (mechanical, pharmacological, or both or none) that was provided perioperatively to patients undergoing surgery. Prior to implementation of the STEP protocol (STEP-P) standard of care involved a population-based "one size fits all" approach rather than a risk stratified approach.
Control group
Historical

Outcomes
Primary outcome [1] 320089 0
Change in postoperative thromboembolic event rates.
Patient safety indicators’ (PSIs) were used to assess the incidence of adverse events including postoperative thromboembolism and bleeding, using the International Statistical Classification of Disease (ICD). The agency of healthcare research and quality (AHRQ) has developed a set of internationally recognised ‘patient safety indicators (PSIs) that measure the quality of healthcare provided by institutions using readily available inpatient administrative data24. These PSIs codes are commonly utilised for QI research. The AHRQ PSIs have been adapted to the Australian healthcare system using codes from the 10th revision of the ICD Australian Modification (ICD-10-AM). These are known as the AusPSIs.
Our postoperative TE and bleeding events were identified using ICD-10-AM codes assigned for each episode of care and extracted from the hospital’s administrative data warehouse that reports to the Victorian Admitted Episodes Dataset (VAED). The VAED collects demographic, clinical and administrative details for all episodes of care at Victorian healthcare organisations.
Timepoint [1] 320089 0
Baseline, 20 weeks post initial intervention (primary endpoint), 2 years after initial intervention (gap analysis phase), and 15 months after final intervention (final implementation, final timepoint)
Secondary outcome [1] 370503 0
Change in postoperative bleeding rates.

Patient safety indicators’ (PSIs) were used to assess the incidence of adverse events including postoperative thromboembolism and bleeding, using the International Statistical Classification of Disease (ICD). The agency of healthcare research and quality (AHRQ) has developed a set of internationally recognised ‘patient safety indicators (PSIs) that measure the quality of healthcare provided by institutions using readily available inpatient administrative data24. These PSIs codes are commonly utilised for QI research. The AHRQ PSIs have been adapted to the Australian healthcare system using codes from the 10th revision of the ICD Australian Modification (ICD-10-AM). These are known as the AusPSIs.
Our postoperative TE and bleeding events were identified using ICD-10-AM codes assigned for each episode of care and extracted from the hospital’s administrative data warehouse that reports to the Victorian Admitted Episodes Dataset (VAED). The VAED collects demographic, clinical and administrative details for all episodes of care at Victorian healthcare organisations.
Timepoint [1] 370503 0
Baseline, 20 weeks post initial intervention (primary endpoint), 2 years after initial intervention (gap analysis phase), and 15 months after final intervention (final implementation, final timepoint)

Eligibility
Key inclusion criteria
All surgical oncology admissions to our institutions. No exclusions.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No exclusion criteria

Study design
Purpose of the study
Prevention
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 before (baseline) and after (implementation) trial compared postoperative thromboembolism and bleeding rates in patients before and after STEP-QIP implementation. Allocations to the "before" stage included all surgical admissions before implementation of the STEP-QIP program. This cohort determined the baseline rates of postoperative and bleeding rates and included all surgical admission from the 1st of June 2013 until 30th of July 2014. Implementation of the STEP-QIP began on the 1st of August 2014. All surgical admission after 1st of August 2014 were allocated and handled as the "after" stage. Implementation of the STEP-QIP occurred over 3 phases - 1) Initial implementation (1st of August 2014 until December 2014), this was followed by 2) Gap analysis phase (January 2015 until December 2016) and then the 3) Final implementation phase (January 2017 - March 2018).
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size was determined by the normal surgical case flow and hospital case mix. The national rates of postoperative venous thromboembolism is 1.2 per 1,000 surgical admissions in Australia. The baseline rate at our institution was 3.1 per 1,000 surgical admissions. We set a primary endpoint target reduction of 50% in thromboembolic rates and aimed to achieve a greater than 80% compliance with the STEP-QIP. We used descriptive statistics to describe compliance rates, thromboembolic and bleeding rates and reported this data in terms of absolute numbers, percentage and rates. TE and bleeding rates are analysed using Fisher’s exact test and reported in terms of relative risk reduction (RRR) with Altman’s method for 95% confidence intervals. All statistical tests were two-sided and conducted as a significance level of 0.05. Statistical analysis was performed using Stata version 12.1 (StataCorp LP, Texas, USA).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
1/10/2013
Date of last participant enrolment
Anticipated
Actual
31/03/2018
Date of last data collection
Anticipated
Actual
26/04/2019
Sample size
Target
20000
Accrual to date
Final
24953
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13762 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 26511 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 302802 0
Hospital
Name [1] 302802 0
Peter MacCallum Cancer Centre Auxillary Service
Country [1] 302802 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan Street, Melbourne, VIC 3000
Country
Australia
Secondary sponsor category [1] 302749 0
Hospital
Name [1] 302749 0
Department of Anaesthesia, Perioperative and Pain medicine, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne VIC 3000
Address [1] 302749 0
305 Grattan Street, Melbourne, VIC 3000
Country [1] 302749 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303389 0
Peter MacCallum Cancer Centre Hospital Reseach Ethics Commitee
Ethics committee address [1] 303389 0
Peter MacCallum Cancer Centre
305 Grattan Street, Melbourne, VIC3000
Ethics committee country [1] 303389 0
Australia
Date submitted for ethics approval [1] 303389 0
02/05/2013
Approval date [1] 303389 0
19/06/2013
Ethics approval number [1] 303389 0
13/73 L

Summary
Brief summary
This study aims to evaluate the efficacy, safety and sustainability of an individualised approach to postoperative thromboembolism prevention in cancer surgery patients.

Who is it for?
You may be eligible to join this study if you are aged 16 years or above, and are scheduled to undergo cancer surgery at the Peter MacCallum Cancer Centre.

Study details
Participants in this study are categorised into low, intermediate and high risk profiles for thromboembolism, according to surgical procedure and baseline medical risk. Expert-endorsed risk-specific thromboprophylaxis strategies are then applied. These strategies include mechanical or drug intervention that were administered at a specific time point, duration and appropriate dose. For example patients undergoing major surgery (e.g. bowel resection) were classified as high risk profile and received mechanical compression devices and stockings, as well as blood thinning medications for at least 7 days after surgery. Patients undergoing lower risk endoscopic procedures were only advised to have early mobilisation after their procedure.

Postoperative thromboembolism and bleeding rates will be compared before and after implementation of this protocol.

If effective, it is hoped that this flexible approach can be translated to surgical populations at other institutions.
Trial website
Trial related presentations / publications
Public notes
Data for first participant was analysed from the 1st of June 2013. Application for ethics approval was submitted on the second of May 2013. This historical data point was prior to the date of ethical approval (19/06/2013), however this was only retrospectively accessed on the 1st of October 2013, after ethics approval was obtained. These data points are stored and readily available on the hospital’s administrative data warehouse that reports to the Victorian Admitted Episodes Dataset (VAED). The VAED collects demographic, clinical and administrative details for all episodes of care at Victorian healthcare organisations. The actual date of first participant enrolment was therefore on the 1st of October 2013. All data points prior to the 1st of August 2014 were baseline data (standard care) and did not involve any active intervention.

Contacts
Principal investigator
Name 93506 0
Dr Rani Chahal
Address 93506 0
Peter MacCallum Cancer Centre
305 Grattan St, Melbourne, VIC 3000
Country 93506 0
Australia
Phone 93506 0
+61 3 8559 5000
Fax 93506 0
Email 93506 0
[email protected]
Contact person for public queries
Name 93507 0
A/Prof Kate Burbury
Address 93507 0
Peter MacCallum Cancer Centre
305 Grattan St, Melbourne, VIC 3000
Country 93507 0
Australia
Phone 93507 0
+61 3 8559 5000
Fax 93507 0
Email 93507 0
[email protected]
Contact person for scientific queries
Name 93508 0
Dr Rani Chahal
Address 93508 0
Peter MacCallum Cancer Centre
305 Grattan St, Melbourne, VIC 3000
Country 93508 0
Australia
Phone 93508 0
+61 3 8559 5000
Fax 93508 0
Email 93508 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data collected during the trial after approval from Peter MacCallum Cancer Centre
When will data be available (start and end dates)?
Available for 5 years after publication
Available to whom?
Researchers, Case by case basis
Available for what types of analyses?
To achieve aims in the approved proposal
How or where can data be obtained?
Access subject to approval by Principal investigator


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2118Ethical approval    377612-(Uploaded-28-05-2019-14-41-56)-Study-related document.pdf
2119Study protocol    377612-(Uploaded-16-05-2019-12-47-24)-Study-related document.doc



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.