Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000188538
Ethics application status
Approved
Date submitted
18/01/2024
Date registered
27/02/2024
Date last updated
9/08/2024
Date data sharing statement initially provided
27/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot study of preoperative Roxadustat in patients undergoing major surgery.
Scientific title
Hypoxic Enhancement Before Major Surgery (HYPE): A pilot randomised controlled trial of preoperative Roxadustat vs placebo in patients undergoing major surgery, assessing safety, effectiveness and feasibility.
Secondary ID [1] 311365 0
None
Universal Trial Number (UTN)
Trial acronym
HYPE Pilot Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postoperative Complications 332634 0
Surgical site infection 332893 0
Condition category
Condition code
Surgery 329338 329338 0 0
Other surgery
Infection 329609 329609 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Roxadustat 100mg oral capsules taken on alternate days for four days up to and including the day of surgery i.e. 1st dose 4 days before surgery, 2nd dose 2 days before surgery, final dose on day of surgery. Adherence will be documented by participants in a treatment diary and checked by research team on day of surgery.
Intervention code [1] 327809 0
Treatment: Drugs
Comparator / control treatment
Placebo capsules identical in appearance with TGA approved StarCap 1500 Starch Excipient (contains maize starch and pre-gelatinised maize starch).
Control group
Placebo

Outcomes
Primary outcome [1] 337159 0
A composite of any acute preoperative illness prompting participant to discontinue drug or to seek medical assessment AND/OR any hospital acquired complication (HAC) using the Australian Commission on Safety and Quality in Healthcare definitions.
Timepoint [1] 337159 0
Day of surgery, day of discharge, postoperative day 30.
Secondary outcome [1] 430882 0
Cellular glycolysis (circulating immune cells)
Timepoint [1] 430882 0
Day of surgery (pre-anaesthesia)
Secondary outcome [2] 430883 0
Immune function (circulating immune cells)
Timepoint [2] 430883 0
Day of surgery (pre-anaesthesia)
Secondary outcome [3] 430884 0
Postoperative C-Reactive Protein
Timepoint [3] 430884 0
Postoperative days 1, 2 and 3
Secondary outcome [4] 430885 0
Postoperative Troponin
Timepoint [4] 430885 0
Postoperative days 1, 2 and 3
Secondary outcome [5] 430886 0
Surgical Site Infection (CDC Criteria)
Timepoint [5] 430886 0
Postoperative Day 30
Secondary outcome [6] 430887 0
Length of stay
Timepoint [6] 430887 0
Postoperative Day 30
Secondary outcome [7] 430888 0
Readmission within 30 days
Timepoint [7] 430888 0
Postoperative Day 30
Secondary outcome [8] 430889 0
Days alive and out of hospital in first 30 days
Timepoint [8] 430889 0
Postoperative Day 30
Secondary outcome [9] 430890 0
Acute kidney injury
Timepoint [9] 430890 0
Postoperative days 1, 2 and 3
Secondary outcome [10] 430891 0
Mortality
Timepoint [10] 430891 0
Postoperative Day 30, 1 year after surgery
Secondary outcome [11] 430892 0
Enrolment rate equal to or greater than 50 patients/ centre/ year.
Timepoint [11] 430892 0
Study end
Secondary outcome [12] 430893 0
Treatment compliance
Timepoint [12] 430893 0
Day of surgery

Eligibility
Key inclusion criteria
1. Age 18 years or over
2. Undergoing elective major surgery including the following procedures: Oesophagectomy; Gastrectomy; Small bowel resection; Large bowel resection; Hepatectomy; Splenectomy; Pancreatectomy; Nephrectomy; Prostatectomy; Cystectomy; Adrenalectomy; Abdominal aneurysm repair (Open); Femoral-Popliteal Bypass; Total hip replacement; Total knee replacement; Spinal surgery (3 levels or more).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inability to provide informed consent
2. Peanut or soya allergy
3. Current viral or bacterial infection
4. Pregnancy or breast feeding
5. Epilepsy
6. Severe liver disease (Childs Pugh C)

Study design
Purpose of the study
Prevention
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)
Permuted block randomisation, stratified according to surgery type (open abdominal, laparoscopic abdominal, orthopaedic, other).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A convenience sample was chosen to demonstrate phase 2 safety. Analysis will be predominantly qualitative.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/04/2024
Actual
14/06/2024
Date of last participant enrolment
Anticipated
14/12/2025
Actual
Date of last data collection
Anticipated
14/12/2026
Actual
Sample size
Target
150
Accrual to date
13
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 26046 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 41893 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 315625 0
Government body
Name [1] 315625 0
National Health and Medical Research Council
Country [1] 315625 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital
Address
197 Wellington Street ,Perth, WA 6000
Country
Australia
Secondary sponsor category [1] 317719 0
None
Name [1] 317719 0
Address [1] 317719 0
Country [1] 317719 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314508 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 314508 0
Level 2, Education Building, Fiona Stanley Hospital 14 Barry Marshall Parade MURDOCH Western Australia 6150
Ethics committee country [1] 314508 0
Australia
Date submitted for ethics approval [1] 314508 0
01/11/2023
Approval date [1] 314508 0
12/12/2023
Ethics approval number [1] 314508 0
RGS0000006528

Summary
Brief summary
Complications after major surgery are common and decrease survival in the short and long-term. Tissue hypoxia (low oxygen) is established as a driver of postoperative complications. All complex cells can adapt to low oxygen conditions, over a period of hours to days, by activating the highly conserved hypoxia inducible factor (HIF) pathway. Roxadustat is a first-in-class oral prolyl hydroxylase inhibitor that increases HIF signalling and is currently marketed for the treatment of anaemia in chronic kidney disease. Brief preoperative Roxadustat exposure stands to prime cells to function well under the anticipated hypoxic stress of major surgery, a clinical insult that is unique due to its precise timing. In particular, Roxadustat may enhance immune cell function and healing in the hypoxic microenvironment of the surgical wound, thereby reducing the burden of surgical site infection. Hypothesis: A definitive phase 3 randomised controlled trial of preoperative roxadustat vs placebo in patients undergoing major noncardiac surgery is safe, feasible and justified.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131834 0
A/Prof Andrew Toner
Address 131834 0
Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, 197 Wellington Street, Perth, WA 6000
Country 131834 0
Australia
Phone 131834 0
+610892242244
Fax 131834 0
Email 131834 0
[email protected]
Contact person for public queries
Name 131835 0
Andrew Toner
Address 131835 0
Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, 197 Wellington Street, Perth, WA 6000
Country 131835 0
Australia
Phone 131835 0
+6189224 2244
Fax 131835 0
Email 131835 0
[email protected]
Contact person for scientific queries
Name 131836 0
Andrew Toner
Address 131836 0
Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, 197 Wellington Street, Perth, WA 6000
Country 131836 0
Australia
Phone 131836 0
+610892242244
Fax 131836 0
Email 131836 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?
Individual participant data underlying published results only
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
Researchers who provide a methodologically sound proposal
Available for what types of analyses?
For IPD meta-analyses
How or where can data be obtained?
Access subject to approvals by 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.