Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001267943
Ethics application status
Approved
Date submitted
25/09/2020
Date registered
25/11/2020
Date last updated
7/02/2023
Date data sharing statement initially provided
25/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
An assessment of the impact of midodrine on early mobilisation after hip replacement surgery
Scientific title
A randomised trial to assess the impact of midodrine on early mobilisation after total hip arthroplasty
Secondary ID [1] 302405 0
Nil known
Universal Trial Number (UTN)
The Universal Trial Number (UTN) is U1111-1258-7550
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Orthostatic intolerance 319197 0
Total hip arthroplasty 319198 0
Condition category
Condition code
Cardiovascular 317161 317161 0 0
Other cardiovascular diseases
Musculoskeletal 317162 317162 0 0
Osteoarthritis
Surgery 317163 317163 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients enrolled in the trial will receive a dose of 20mg of midodrine, or placebo, two hours prior to mobilisation on the first day following surgery. This will be prescribed and recorded on the patients usual medication prescription sheet as MIDODRINE TRIAL MEDICATION. The randomisation will be concealed to both patient and nurse administering the medication.
Intervention code [1] 318690 0
Prevention
Comparator / control treatment
Placebo tablets will be identical in appearance to the midodrine tablets. The composition of the placebo tablets is currently unknown.
Control group
Placebo

Outcomes
Primary outcome [1] 325247 0
Ability to successfully mobilise a minimum of 5m during the first attempt on day 1 following total hip arthroplasty. The process will be as follows:
• Supine BP taken by a physiotherapist using an automated sphygmomanometer
• Patient then sits on edge of bed and does marching on the spot exercises (whilst sitting)
• If successful proceed to stand them up (on day 1 this is with the assistance of at least one person or a frame)
• Standing blood pressure taken after 1 min and 3min
• If standing OK then proceed to try walking
• The primary outcomes measure is whether they are able to complete the 5m walk, with or without assistance, on the first attempt (Yes/No)
• Any aids required will also be recorded – No aid/ x1 assist/ x2 assist / frame
Timepoint [1] 325247 0
This will be measured during the 1st attempt to mobilise on the day following surgery
Secondary outcome [1] 387323 0
Orthostatic hypotension
Defined as systolic drop of >20mmHg or a diastolic drop of 10mmHg as measured using an automated sphygmomanometer

Timepoint [1] 387323 0
This will be measured during the 1st attempt to mobilise on the day following surgery
Secondary outcome [2] 387324 0
Orthostatic intolerance will be assessed by the physiotherapist assisting the 1st mobilisation. It is defined as an inability to mobilise caused by the onset of any/all of the following symptoms after sitting or standing from a supine position whether or not there is a recorded fall in blood pressure:
Dizziness
Blurred vision
Nausea or vomiting
Syncope
Timepoint [2] 387324 0
The first attempt to mobilize on the morning following surgery
Secondary outcome [3] 387326 0
Supine hypotension as recorded by the nurse in the patients usual observation chart on day 1 following surgery while supine. This will be defined as a recorded systolic BP < 100mmHg at any time during normal observations (minimum 4 hourly unless otherwise specified).
Timepoint [3] 387326 0
Day 1 following surgery
Secondary outcome [4] 387327 0
Side effects to Midodrine (in the 24h period following administration) as documented in the patients observation chart or in the clinical progress notes.
Supine hypertension (SAP >180mmHg, or DAP > 110mmHg)
Severe bradycardia (HR < 40/min)
Urinary retention requiring catheterisation
Severe pruritus
Timepoint [4] 387327 0
Day 1 following surgery
Secondary outcome [5] 387328 0
Incidence of medical emergency response calls for hypotension as recorded in the patients medical file.
Timepoint [5] 387328 0
Day 1 following surgery
Secondary outcome [6] 387329 0
Hospital length of stay as recorded in the patients medical file
Timepoint [6] 387329 0
Measured in days at the time of acute hospital discharge
Secondary outcome [7] 387330 0
Pain score before and after physiotherapy on numeric rating scale from 0 to 10. This will be on the first physiotherapy session on the morning following surgery.
Timepoint [7] 387330 0
The morning following surgery

Eligibility
Key inclusion criteria
Adults, aged > 18 years old
Elective unilateral total hip arthroplasty under spinal anaesthesia
Mentally competent to provide informed own written consent in English
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Spinal anaesthesia not planned, or refused by patient
Chronic renal impairment
Creatinine >2mg/dL or 180micmol/L
Clinical evidence of liver failure
Heart failure
NYHA class 3 or 4
Ejection fraction < 30%
Glaucoma
Revision hip arthroplasty
Hip resurfacing surgery
Significant preoperative neuromuscular condition limiting mobility
Anaemia
Preoperative haemoglobin concentration < 110g/L
Prior diagnosis of postural hypotension
Patients taking digoxin
Pregnant/Lactating Women
Thyrotoxicosis
Pheochromocytoma
Allergy to Midodrine
Chronic urinary retention
Significant neuromuscular condition limiting mobility
Co-Enrolment in another vasopressor clinical trial

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)
A clinician, who is not associated with site recruitment, will create a randomised allocation sequence, concealed in opaque envelopes. The allocation will indicate whether the participant receives midodrine or placebo. The active medication or placebo will not be identifiable and stored in identical packaging. Each participant will be allocated a single envelope (containing midodrine 20mg (in 4x5mg tablets) or placebo (also in 4 tablets)). Randomisation and allocation will occur on the day of surgery, prior to initiation of anaesthesia. The medication will be stored with the patient’s other medications during the 1st 24h and then disposed of if not given.   
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
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
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Power Analysis: The sample size estimation is informed by a baseline estimation of 40% of patients who fail to mobilise 5m on the first attempt the day after surgery. To power the study for a reduction to 10%, power 0.8 alpha 0.05, = 76 patients, allowing for 10% loss to follow-up = 84 patients in total.
At the half-way point of the trial an interim analysis will be performed to recalculate power and ensure group sizes are adequate. The interim analysis will be performed by an independent clinician or statistician, blinded to the treatment allocation.
Statistical Analysis: Dichotomous outcomes will be analysed using a Chi-Square test or Fisher Exact Test where appropriate. Continuous data will be analysed with a Student’s T-test.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
After the interim analysis, the data and safety monitoring board recommended the trial be stopped early. The reasons for this were (1) a p-value for efficacy of 1.00, (2) a low probability of demonstrating a statistical difference, even with adjustment of the sample size to account for the lower-than-expected event rate
Date of first participant enrolment
Anticipated
14/12/2020
Actual
8/02/2021
Date of last participant enrolment
Anticipated
30/06/2021
Actual
10/02/2022
Date of last data collection
Anticipated
9/07/2021
Actual
11/02/2022
Sample size
Target
84
Accrual to date
Final
42
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 17641 0
Osborne Park Hospital - Stirling
Recruitment hospital [2] 23919 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 31391 0
6021 - Stirling
Recruitment postcode(s) [2] 39412 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 306828 0
Charities/Societies/Foundations
Name [1] 306828 0
Charlies foundation for research
Country [1] 306828 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner and Osborne Park Hospital Group
Address
Hospital Avenue
Nedlands
WA 6009
Country
Australia
Secondary sponsor category [1] 307385 0
Individual
Name [1] 307385 0
Dr Mark Lennon
Address [1] 307385 0
Department of Anaesthesia
Sir Charles Gairdner Hospital
Hospital avenue
Nedlands
WA 6009
Country [1] 307385 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306988 0
Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee
Ethics committee address [1] 306988 0
Ethics committee country [1] 306988 0
Australia
Date submitted for ethics approval [1] 306988 0
30/10/2019
Approval date [1] 306988 0
12/06/2020
Ethics approval number [1] 306988 0
RGS0000003096

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

Contacts
Principal investigator
Name 105666 0
Dr Adam Cammerman
Address 105666 0
Dept of Anaesthesia
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands
WA 6009
Country 105666 0
Australia
Phone 105666 0
+61 8 64573011
Fax 105666 0
Email 105666 0
[email protected]
Contact person for public queries
Name 105667 0
Adam Cammerman
Address 105667 0
Dept of Anaesthesia
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands
WA 6009
Country 105667 0
Australia
Phone 105667 0
+61 8 64573011
Fax 105667 0
Email 105667 0
[email protected]
Contact person for scientific queries
Name 105668 0
Adam Cammerman
Address 105668 0
Dept of Anaesthesia
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands
WA 6009
Country 105668 0
Australia
Phone 105668 0
+61 8 64573011
Fax 105668 0
Email 105668 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 that underlie the results reported after deidentification
When will data be available (start and end dates)?
Beginning 3 months following publication for 5 years
Available to whom?
Researchers with a sound proposal
Available for what types of analyses?
To achieve the aims of the proposal
How or where can data be obtained?
Subject to approval from principal investigator: [email protected]


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.