Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000312741
Ethics application status
Approved
Date submitted
13/02/2022
Date registered
18/02/2022
Date last updated
18/02/2022
Date data sharing statement initially provided
18/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Hip fracture surgery and outcomes
Scientific title
Hip Fracture Cohort Study Linking Obesity to Thromboembolism post-Surgery
Secondary ID [1] 306410 0
Nil known
Universal Trial Number (UTN)
U1111-1274-3365
Trial acronym
HipCLOTS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hip fracture surgery complications 325245 0
Condition category
Condition code
Surgery 322642 322642 0 0
Other surgery
Blood 322644 322644 0 0
Clotting disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Exposure: High or low body mass index (BMI) ( WHO classification) in hip fracture patients undergoing surgical fixation between January 2010 till 31 December 2020
The Prince Charles Hospital (TPCH) Hip Fracture unit was established in 2010 and manages approximately 350 hip fracture surgeries on average every year. Since 2015, Australian New Zealand Hip fracture registry (ANZHFR) was established as a collaborative project between societies with an aim to use the collected data to improve the outcomes through appropriate research. For this data linkage study, details of the patients that underwent hip fracture surgery at TPCH over a 10-year period (2010-2020) will be collected from various sources as below:

Hospital admission records (TPCH orthopaedic department database) would contain information on demographics (age, gender, body height, weight, BMI, other nutritional assessment measures as available, namely from malnutritional screening tool, subjective global assessment score), comorbidities (history of venous thromboembolism (VTE), chronic obstructive pulmonary disease (COPD), congestive cardiac failure (CCF), coronary artery disease (CAD), Peripheral vascular disease, chronic kidney disease (CKD), dyslipidaemia, Obstructive sleep apnoea (OSA,) hypertension (HTN), diabetes mellitus (DM), liver and renal disease, smoking status, presence of cancer, treatment with opioids, anticoagulants, antibiotics, immunosuppression, presence of metabolic syndrome (MetS), laboratory parameters including serum albumin, functional status, American Society of Anaesthesiologists (ASA) classification, thromboprophylactic regimen, intraoperative details including tranexamic acid, time to surgery, time to mobilise and postoperative discharge details including length of hospital stay, intensive care unit stay, mortality and complications. MetS will be defined according to the International Diabetes Federation definition as obesity (BMI >30 kg/m2) + any two of raised triglycerides, reduced high density lipoprotein (HDL) cholesterol, raised blood pressure, raised fasting plasma glucose or their alternatives as described.
Intervention code [1] 322839 0
Not applicable
Comparator / control treatment
Hip fracture patients with normal BMI ( 19-29.9 kg/m2) ( WHO classification undergoing surgical fixation will be the control group
Control group
Active

Outcomes
Primary outcome [1] 330441 0
Primary outcome: Thromboembolic complications (venous and arterial) : myocardial infarction, symptomatic deep venous thrombosis, pulmonary embolism, ischaemic stroke.


Diagnosis and complication codes are classified using the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM)33 and retreived from the Qld Hospital Admitted Patient Data Collection (QHAPDC).. Individual charts would be reviewed for missing or ambiguous information. Records of ED presentation, complications will be retrieved through Australian New Zealand Hip fracture registry (ANZHFR),

Occurrence of postoperative complication will be retrieved from the orthopaedic database from regular follow up, ANZ HFR and QH Statistical service branch (SSB) data linkage facility for readmissions from QHAPDC, ED presentations (Non-Hospital Admitted Patient Data Repository, NHAPDR), Clinic appointments for QH (public services) throughout the state




Timepoint [1] 330441 0
at 90 days following hip fracture surgery.
Secondary outcome [1] 406230 0
Thromboembolic complications and other complications (surgical site infection (SSI), major bleeding and transfusion, pneumonia, acute renal failure, mechanical complication, readmission and reoperation, intensive care unit admission, re-presentation to a hospital, cardiovascular death and non-fatal cardiac arrest) including mortality

Diagnosis and complication codes are classified using the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM)33 and retreived from the Qld Hospital Admitted Patient Data Collection (QHAPDC).. Individual charts would be reviewed for missing or ambiguous information. Records of ED presentation, complications will be retrieved through Australian New Zealand Hip fracture registry (ANZHFR),

Occurrence of postoperative complication will be retrieved from the orthopaedic database from regular follow up, ANZ HFR and QH Statistical service branch (SSB) data linkage facility for readmissions from QHAPDC, ED presentations (Non-Hospital Admitted Patient Data Repository, NHAPDR), Clinic appointments for QH (public services) throughout the state and Mortality from Queensland Births Deaths and Marriages registry (QBDMR).

For non-Queensland residents who were operated at TPCH during the study period, where mortality may not be recorded in the QBDMR, mortality status will initially be ascertained through the electronic records linkage to retrieve date of last episode of care within the follow-up period, including admitted, and non-admitted episodes and clinic appointments in the public health system via the QH Statistical Services Branch. In addition, their paper medical record or their Viewer record may be assessed for details such as test results or clinical notes relating to relevant outcomes of interest.
Timepoint [1] 406230 0

Date of surgery (Day 1) till the Date of discharge
Secondary outcome [2] 406231 0
Thromboembolic complications and other complications (surgical site infection (SSI), major bleeding and transfusion, pneumonia, acute renal failure, mechanical complication, readmission and reoperation, intensive care unit admission, re-presentation to a hospital, cardiovascular death and non-fatal cardiac arrest) including mortality

Diagnosis and complication codes are classified using the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM)33 and retreived from the Qld Hospital Admitted Patient Data Collection (QHAPDC).. Individual charts would be reviewed for missing or ambiguous information. Records of ED presentation, complications will be retrieved through Australian New Zealand Hip fracture registry (ANZHFR),

Occurrence of postoperative complication will be retrieved from the orthopaedic database from regular follow up, ANZ HFR and QH Statistical service branch (SSB) data linkage facility for readmissions from QHAPDC, ED presentations (Non-Hospital Admitted Patient Data Repository, NHAPDR), Clinic appointments for QH (public services) throughout the state and Mortality from Queensland Births Deaths and Marriages registry (QBDMR).

For non-Queensland residents who were operated at TPCH during the study period, where mortality may not be recorded in the QBDMR, mortality status will initially be ascertained through the electronic records linkage to retrieve date of last episode of care within the follow-up period, including admitted, and non-admitted episodes and clinic appointments in the public health system via the QH Statistical Services Branch. In addition, their paper medical record or their Viewer record may be assessed for details such as test results or clinical notes relating to relevant outcomes of interest.
Timepoint [2] 406231 0
Date of discharge to Day 137 (with the notional midpoint being Day 90)
Secondary outcome [3] 406232 0
Thromboembolic complications and other complications (surgical site infection (SSI), major bleeding and transfusion, pneumonia, acute renal failure, mechanical complication, readmission and reoperation, intensive care unit admission, re-presentation to a hospital, cardiovascular death and non-fatal cardiac arrest) including mortality.

Diagnosis and complication codes are classified using the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM)33 and retreived from the Qld Hospital Admitted Patient Data Collection (QHAPDC).Individual charts would be reviewed for missing or ambiguous information. Records of ED presentation, complications will be retrieved through Australian New Zealand Hip fracture registry (ANZHFR),

Occurrence of postoperative complication will be retrieved from the orthopaedic database from regular follow up, ANZ HFR and QH Statistical service branch (SSB) data linkage facility for readmissions from QHAPDC, ED presentations (Non-Hospital Admitted Patient Data Repository, NHAPDR), Clinic appointments for QH (public services) throughout the state and Mortality from Queensland Births Deaths and Marriages registry (QBDMR).

For non-Queensland residents who were operated at TPCH during the study period, where mortality may not be recorded in the QBDMR, mortality status will initially be ascertained through the electronic records linkage to retrieve date of last episode of care within the follow-up period, including admitted, and non-admitted episodes and clinic appointments in the public health system via the QH Statistical Services Branch. In addition, their paper medical record or their Viewer record may be assessed for details such as test results or clinical notes relating to relevant outcomes of interest.
Timepoint [3] 406232 0
Day 137 to Day 273 (notional midpoint being Day 180)
Secondary outcome [4] 406233 0
Thromboembolic complications and other complications (surgical site infection (SSI), major bleeding and transfusion, pneumonia, acute renal failure, mechanical complication, readmission and reoperation, intensive care unit admission, re-presentation to a hospital, cardiovascular death and non-fatal cardiac arrest) including mortality.

Diagnosis and complication codes are classified using the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM)33 and retreived from the Qld Hospital Admitted Patient Data Collection (QHAPDC).. Individual charts would be reviewed for missing or ambiguous information. Records of ED presentation, complications will be retrieved through Australian New Zealand Hip fracture registry (ANZHFR),

Occurrence of postoperative complication will be retrieved from the orthopaedic database from regular follow up, ANZ HFR and QH Statistical service branch (SSB) data linkage facility for readmissions from QHAPDC, ED presentations (Non-Hospital Admitted Patient Data Repository, NHAPDR), Clinic appointments for QH (public services) throughout the state and Mortality from Queensland Births Deaths and Marriages registry (QBDMR).

For non-Queensland residents who were operated at TPCH during the study period, where mortality may not be recorded in the QBDMR, mortality status will initially be ascertained through the electronic records linkage to retrieve date of last episode of care within the follow-up period, including admitted, and non-admitted episodes and clinic appointments in the public health system via the QH Statistical Services Branch. In addition, their paper medical record or their Viewer record may be assessed for details such as test results or clinical notes relating to relevant outcomes of interest.
Timepoint [4] 406233 0
Day 273 till until the end of 12-month time period.

Eligibility
Key inclusion criteria
Adult patients 60 years and above, who underwent surgery for hip fracture at TPCH between the years 2010-2020
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Hip fracture patients who were managed with non-surgical options
• Those with co-existing fractures in other areas

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Primary endpoint:
• Thromboembolic complication free survival (TCFS) defined as the time from surgery to the first occurrence of thromboembolic complications or death from any cause (whichever comes first).

Patients will be classified according to the WHO BMI categories into four groups: underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5 to <25 kg/m2), overweight/pre obese (BMI 25 to <30 kg/m2), and obese (BMI 30 kg/m2). The association of BMI categories with other categorial variables of interest will be summarised using cross tabulations and formally tested using Chi square tests or Fisher’s exact test as appropriate. Continuous variables will be summarised using measures of central tendency (mean, median) and spread (standard deviation, interquartile range). For endpoints without any possible loss to follow up (such as in-hospital complications), associations between exposures of interest and the binary outcome (complications yes/no) will be analysed using univariable and multivariable logistic regression analyses with a p<0.1 (for univariable analyses) and p<0.05 (for multivariable analyses); odds ratios with 95% confidence intervals will be presented. Regression models will also explore adjustments for measured confounders such as age, sex, BMI (categorical and continuous), nutritional status and comorbidities. Detailed definitions of the confounders to be explored will be documented in a statistical analysis plan (SAP) that will be finalised prior to the commencement of statistical analyses. Continuous outcomes of interest (e.g. length of stay) will be analysed using linear regression analysis. An alpha value of 0.05 will be used to assess statistical significance.

The time from the date of surgery to the date of first occurrence of any event of interest and the ‘failure type’ of the first occurrence will be noted. Cumulative incidences of each type of ‘failure event’ will be calculated and the cumulative incidence curves will be constructed. Competing risks regression (CRR) analysis will explore associations of cumulative incidences with intraoperative covariates and covariates measured at admission. CRR analyses will also be performed based on the times from the date of discharge to the date of the first occurrence of a failure type (post discharge). Covariates will also include post-operative assessments collected prior to discharge. For patients who experience first events after hospital discharge, landmark regression analyses may be used to explore covariates that are measured post-discharge. Details will be documented in the SAP.

Thromboembolic-complication-free survival (TCFS) of patients within a specific BMI group will be assessed using time-to-event statistical methodology accounting for censoring: Kaplan-Meier curves with log-rank tests and Cox proportional hazards regression models.

Landmark analyses of TCFS may also be performed on sets of patients who have not experienced a thromboembolic complication or death prior to the landmark timepoint.

Sample size justification:
We expect a sample of around 2000-2500 hip fracture patients that underwent surgery at TPCH between 2010-2020. Two approaches to justify this sample size:
(i) Logistic regression for the 90-day endpoint, two groups of equal size (e.g. dichotomised on the median of a potential covariate) each of 1250 to 1500 patients. Likelihood ratio chi-squared test. Average 90-day event rate of 5%. With n=2500, no censoring, an odds-ratio of 1.673 can be detected with 80% power (e.g. 3.8% vs 6.2%). With n=3000, an odds-ratio of 1.601 can be detected with 80% power (e.g. 3.9% vs 6.1%). Software: SAS 9.4.
(ii) TCFS (composite time to event endpoint). Two groups of equal size (e.g. dichotomised on the median of a potential covariate) each of 1250 patients (total n =2500). Log-rank test, two-sided, alpha=0.05. Average 90-day event rate of 5% (i.e. 95% TCFS). Follow-up is the same in each group but within each group 50% are followed-up for between 6 months and 9 months, and 50% are followed-up for between 9 months and 12 months. No patients followed-up beyond 12 months. With n=2500 and average TCFS of 95% at 3 months, we expect to see 355 events (thromboembolic complications or deaths) and the log-rank test has at least 80% power for a hazard ratio of 0.741 (e.g. TCFS at 3 months of 95.725% versus 94.275%, i.e. a difference of 1.5% in TCFS between the two groups at 3 months). Software: East 6.5.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/02/2022
Actual
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
2500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 21702 0
The Prince Charles Hospital - Chermside
Recruitment postcode(s) [1] 36754 0
4032 - Chermside

Funding & Sponsors
Funding source category [1] 310762 0
Government body
Name [1] 310762 0
Queensland Advancing Clinical Research Fellowship
Country [1] 310762 0
Australia
Primary sponsor type
Individual
Name
Usha Gurunathan
Address
Department of Anaesthesia, The Prince Charles Hospital, Rode Road, Chermside, Queensland 4032
Country
Australia
Secondary sponsor category [1] 311996 0
None
Name [1] 311996 0
Address [1] 311996 0
Country [1] 311996 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310338 0
The Prince Charles Hospital Human Resarch Ethics Committee
Ethics committee address [1] 310338 0
Ethics committee country [1] 310338 0
Australia
Date submitted for ethics approval [1] 310338 0
Approval date [1] 310338 0
14/10/2020
Ethics approval number [1] 310338 0

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

Contacts
Principal investigator
Name 117290 0
Dr Usha Gurunathan
Address 117290 0
Department of Anaesthesia, The Prince Charles Hospital, Rode road, Chermside, Queensland, 4032
Country 117290 0
Australia
Phone 117290 0
+61 7 3139 4995
Fax 117290 0
Email 117290 0
[email protected]
Contact person for public queries
Name 117291 0
Usha Gurunathan
Address 117291 0
Department of Anaesthesia, The Prince Charles Hospital, Rode road, Chermside, Queensland, 4032
Country 117291 0
Australia
Phone 117291 0
+61 7 3139 4995
Fax 117291 0
Email 117291 0
[email protected]
Contact person for scientific queries
Name 117292 0
Usha Gurunathan
Address 117292 0
Department of Anaesthesia, The Prince Charles Hospital, Rode road, Chermside, Queensland, 4032
Country 117292 0
Australia
Phone 117292 0
+61 7 3139 4995
Fax 117292 0
Email 117292 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
This is a retrospective study and individual participant data may not be useful. However, data sharing is undecided at the moment and will be at the discretion of the principal investigator


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
No additional documents have been identified.