Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001342909
Ethics application status
Approved
Date submitted
14/10/2020
Date registered
14/12/2020
Date last updated
17/04/2024
Date data sharing statement initially provided
14/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
MObILE study - Midodrine effect on Orthostatic IntoLErance after hip and knee replacements
Scientific title
A randomised placebo-controlled trial to determine the effectof oral Midodrine hydrochloride to prevent orthostatic intolerance during mobilisation following total hip and knee arthroplasty
Secondary ID [1] 302513 0
None
Universal Trial Number (UTN)
U1111-1198-0331
Trial acronym
MObILE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Orthostatic Intolerance 319381 0
Total Hip arthroplasty 319382 0
Total Knee arthroplasty 319383 0
Orthostatic Hypotension 319384 0
Condition category
Condition code
Surgery 317351 317351 0 0
Other surgery
Cardiovascular 317352 317352 0 0
Diseases of the vasculature and circulation including the lymphatic system
Neurological 317639 317639 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral Midodrine Hydrochloride 10mg administered five times in the early postoperative period;
Day of surgery; 1 tablet oral every 4 hours for 2 doses
Postoperative day 1; 1 tablet oral every 4 hours for 3 doses
Drug administration will be carried out by a ward nurse. Prescription records and administration records will be monitored by a researcher daily, whilst patients are in the study.
Intervention code [1] 318808 0
Prevention
Intervention code [2] 318809 0
Treatment: Drugs
Comparator / control treatment
Placebo oral tablet;
white placebo tablet containing inactive ingredients, placed in a dark green opaque gelatin capsule (the active study drug will be placed in the same type of capsule to look identical)
Control group
Placebo

Outcomes
Primary outcome [1] 325394 0
The primary outcome is the incidence of orthostatic intolerance in the sitting or standing position during the first mobilisation after surgery.

Orthostatic intolerance will be evaluated with a standardised symptom checklist, which we previously developed for an observational study (1). The checklist is based on the defined symptoms characterising orthostatic intolerance (i.e. dizziness, nausea, vomiting, feeling of heat, blurred vision and ultimately syncope). The described symptoms have also been used as the basis for identification in previous studies. The mobilisation procedure will be standardised to supine rest (5 min), sitting on the hospital bed with feet resting on the floor (3 min), and mobilising to standing using a gutter frame and shifting body weight from one leg to the other (3 min).

1. Skarin MU, Rice DA, McNair PJ, Kluger MT. Orthostatic intolerance following hip arthroplasty: Incidence, risk factors and effect on length of stay: a prospective cohort study. European Journal of Anaesthesiology 2018.
Timepoint [1] 325394 0
Surgery day, approx 6 hours after surgery
Secondary outcome [1] 387764 0
Incidence of orthostatic intolerance in the sitting or standing position during mobilisation on postoperative day 1.

Orthostatic intolerance will be evaluated with a standardised symptom checklist, which we previously developed for an observational study. The checklist is based on the defined symptoms characterising orthostatic intolerance (i.e. dizziness, nausea, vomiting, feeling of heat, blurred vision and ultimately syncope). The described symptoms have also been used as the basis for identification in previous studies. The mobilisation procedure will be standardised to supine rest (5 min), sitting on the hospital bed with feet resting on the floor (3 min), and mobilising to standing using a gutter frame and shifting body weight from one leg to the other (3 min).
Timepoint [1] 387764 0
In the morning of postoperative day 1, approx 24 hours after surgery
Secondary outcome [2] 387766 0
Incidence of orthostatic hypo-tension (decrease in systolic arterial pressure greater than 20 mmHg or diastolic arterial pressure greater than 10 mmHg).

Hemodynamic responses to mobilisation will be captured non-invasively by photoplethysmography by finger cuffs placed on the second and third fingers of the non-dominant hand using the CNAP technology (CNSystems Medizintechnik AG, Graz, Austria).
Timepoint [2] 387766 0
Same two time points as the primary outcome (orthostatic intolerance) is assessed;
1. Surgery day, approx 6 hours after surgery
2. In the morning of postoperative day 1, approx 24 hours after surgery
Secondary outcome [3] 387769 0
Length of hospital stay (days from admission - discharge) will be assessed by extracting data from the electronic medical hospital records
Timepoint [3] 387769 0
At discharge from hospital
Secondary outcome [4] 387771 0
Adverse Events will be reviewed individually in real time while the drug is being administered. Information will be collected from the patient, the nurse and the medical team, as well as from medical and nursing records.
Known/possible side effects are;
Chills
Pruritus, mainly scalp
Piloerection
Paraesthesia, mainly scalp
Urinary retention
Supine hypertension
Timepoint [4] 387771 0
Regularly during surgery day and postoperative day 1. Medical and nursing records covering the entire patient in-hospital stay will be reviewed.

Eligibility
Key inclusion criteria
18 yr or older
Elective primary unilateral total hip or total knee arthroplasty
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Supine hypertension >180 mmHg preoperatively
Chronic kidney disease (eGFR below 60 mL/min/1.73m2 for more than 3 months)
Hepatic failure
Glaucoma
Chronic urinary retention requiring treatment
Taking doxazosin
Documented recurrent or chronic orthostatic intolerance
Known autonomic nervous system dysfunction
TIA or stroke within the last 12 months
Pregnant
Revision surgery
Unable to walk pre-operatively
Unable to speak or understand English

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)
The researcher recruiting patients to the study is blinded to the allocation. Allocation involves contacting the holder (the hospital in-house pharmacy) of the allocation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Stratification by:
Sex (female/male)
Type of surgery (total hip/total knee)
Type of anaesthesia (general/regional)
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 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
This study will be conducted as a superiority trial. The calculated sample size is based on the incidence of orthostatic intolerance at 6h after surgery (based on two previous trials of early mobilisation after total hip arthroplasty), which showed 37.3% and 42% incidence of orthostatic intolerance at 6h after surgery, we calculated that 158 patients would be needed to detect an absolute reduction in orthostatic intolerance from 40 to 20% with a power (1-beta) of 80% and a two-sided a = 0.05. To account for an estimated 5% drop out rate, we conservatively plan to include a total of 170 patients.

Statistical analysis will be undertaken as intention to treat at all levels. Study enrollment and retention will be described using a CONSORT diagram. Baseline characteristics will be compared between the two groups. Primary outcome: The incidence of orthostatic intolerance is considered a binary outcome (YES/NO – mobilisation procedure had to be terminated due to orthostatic intolerance symptoms). Orthostatic intolerance will be compared between the midodrine and placebo groups using a Chi-square test. In addition, relative risk ratios with 95% confidence intervals will be calculated for the midodrine group relative to the placebo group, with a relative risk less than 1.0 indicating a beneficial effect. Secondary outcomes: The incidence of orthostatic intolerance is considered a binary outcome (YES/NO – decrease in systolic or diastolic arterial pressures greater than 20 or 10mmHg, respectively, compared to supine position), and will be compared between allocation groups using the chi-square test. Hemodynamic variables will be analysed using two way ANOVAs with factors of position (supine, sitting, standing) and group (midodrine, placebo) as well as factors of position (supine, sitting, standing) and orthostatic intolerance outcome (YES/NO).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/01/2021
Actual
19/01/2021
Date of last participant enrolment
Anticipated
31/12/2023
Actual
20/12/2023
Date of last data collection
Anticipated
31/03/2024
Actual
31/03/2024
Sample size
Target
170
Accrual to date
Final
170
Recruitment outside Australia
Country [1] 23058 0
New Zealand
State/province [1] 23058 0
Auckland

Funding & Sponsors
Funding source category [1] 306952 0
Charities/Societies/Foundations
Name [1] 306952 0
Auckland Medical Research Foundation (AMRF)
Country [1] 306952 0
New Zealand
Funding source category [2] 306963 0
Government body
Name [2] 306963 0
Lottery Grants Board/Lottery Health Research Foundation
Country [2] 306963 0
New Zealand
Primary sponsor type
Hospital
Name
Waitemata District Health Board
Address
North Shore Hospital
Private Bag 93503
North Shore, Auckland 0740
Country
New Zealand
Secondary sponsor category [1] 307525 0
None
Name [1] 307525 0
Address [1] 307525 0
Country [1] 307525 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307089 0
The Central Health and Disability Ethics Committees
Ethics committee address [1] 307089 0
Ethics committee country [1] 307089 0
New Zealand
Date submitted for ethics approval [1] 307089 0
10/10/2017
Approval date [1] 307089 0
07/12/2017
Ethics approval number [1] 307089 0
17/CEN/209

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

Contacts
Principal investigator
Name 105990 0
Dr Michal Kluger
Address 105990 0
Health New Zealand, Te Whatu Ora, Waitemata
Country 105990 0
New Zealand
Phone 105990 0
+64 21 684022
Fax 105990 0
Email 105990 0
[email protected]
Contact person for public queries
Name 105991 0
Michal Kluger
Address 105991 0
Health New Zealand, Te Whatu Ora, Waitemata
Country 105991 0
New Zealand
Phone 105991 0
+64 21 684022
Fax 105991 0
Email 105991 0
[email protected]
Contact person for scientific queries
Name 105992 0
Michal Kluger
Address 105992 0
Health New Zealand, Te Whatu Ora, Waitemata
Country 105992 0
New Zealand
Phone 105992 0
+64 21 684022
Fax 105992 0
Email 105992 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


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.