Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613001021763
Ethics application status
Approved
Date submitted
11/09/2013
Date registered
13/09/2013
Date last updated
6/08/2019
Date data sharing statement initially provided
6/08/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Treatment of disordered blood pressure in spinal cord injury
Scientific title
A double-blind, placebo controlled, crossover study of a nocturnal dose of captopril to determine its effect on diurnal blood pressure and orthostatic symptoms in people with spinal cord injury
Secondary ID [1] 283186 0
Nil
Universal Trial Number (UTN)
U1111-1147-8242
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Orthostatic intolerance 290044 0
Hypotension 290045 0
Diurnal blood pressure 290046 0
Nocturnal polyuria 290047 0
Spinal cord injury 290048 0
Condition category
Condition code
Cardiovascular 290423 290423 0 0
Other cardiovascular diseases
Neurological 290424 290424 0 0
Other neurological disorders
Injuries and Accidents 290455 290455 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Captopril, orally, nightly, starting at 25mg and uptitrating by 25mg a week to a maximum of 100mg over a 4 week titration phase, followed by maintenance phase for 4 weeks at the highest dose reached. Unused capsules to be returned at the end of each treatment arm. Washout period of 2 weeks between treatment arms.
Intervention code [1] 287913 0
Treatment: Drugs
Comparator / control treatment
Placebo - microcellulose capsule
Placebo and captopril capsules are packaged to look identical
Control group
Placebo

Outcomes
Primary outcome [1] 290449 0
Mean daytime blood pressure - measured by ambulatory blood pressure monitoring
Timepoint [1] 290449 0
Before and after each treatment arm
Secondary outcome [1] 304545 0
Degree of nocturnal dipping - ratio of mean night:day systolic blood pressure as measured by ambulatory blood pressure monitoring
Timepoint [1] 304545 0
Before and after each treatment arm
Secondary outcome [2] 304546 0
Orthostatic hypotension questionnaire symptom scale
Timepoint [2] 304546 0
Before and after each treatment arm
Secondary outcome [3] 304547 0
Nocturnal urine production - volume of urine produced overnight expressed as a percentage of the entire day's urine volume; calculated from a diary kept over 3 consecutive days
Timepoint [3] 304547 0
Before and after each treatment arm

Eligibility
Key inclusion criteria
Traumatic spinal cord injury
Age 18 years or greater
Able to provide informed consent
Symptoms of orthostatic intolerance
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Known hypersensitivity to captopril or any other ACE inhibitor
Significant renal impairment
Persistent hyperkalaemia
Recent changes or titration of antihypertensive agents or intention to do so within duration of study
Presence of any other significant medical conditions likely to influence ability to co-operate or prevent adherence to protocol, or where treatment with captopril would put the participant at increased risk of adverse events or drug interactions
Pregnancy or breastfeeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Enrolled participants are allocated sequential randomisation numbers, where the randomisation schedule is held by the Department of Pharmacy, hence the investigators, assessors and participants remain blinded to treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation
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
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample demographics, blood pressure and symptom scores will be described using descriptive and summary statistics. Comparisons of symptoms, blood pressure, autonomic function and urine measures between the treatment and placebo groups will be made using parametric (e.g. paired t-tests) or repeated measures analysis of variance as appropriate. Blood pressure will also be plotted across assessment points. Blood pressure, autonomic functioning and urine measures will be correlated with symptoms.

Assuming a total of 25 patients enter this two-treatment crossover study, the probability is 80 percent that the study will detect a treatment difference at a two-sided 0.05 significance level, if the true difference between treatments is 10 mmHg. This is based on the assumption that the within-patient standard deviation of the systolic blood pressure is 12 mmHg.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
9/08/2013
Actual
9/08/2013
Date of last participant enrolment
Anticipated
Actual
5/12/2013
Date of last data collection
Anticipated
Actual
22/03/2014
Sample size
Target
25
Accrual to date
Final
4
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1500 0
Austin Health - Austin Hospital - Heidelberg

Funding & Sponsors
Funding source category [1] 287936 0
Charities/Societies/Foundations
Name [1] 287936 0
Transport Accident Commission
Country [1] 287936 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
Austin Hospital
145 Studley Road
Heidelberg Vic 3084
Country
Australia
Secondary sponsor category [1] 286663 0
None
Name [1] 286663 0
Address [1] 286663 0
Country [1] 286663 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289864 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 289864 0
Office for Research,
Austin LifeSciences
Austin Health
PO Box 5555
Heidelberg
Victoria
Australia, 3084
Ethics committee country [1] 289864 0
Australia
Date submitted for ethics approval [1] 289864 0
22/02/2013
Approval date [1] 289864 0
02/05/2013
Ethics approval number [1] 289864 0
H2013 / 04981

Summary
Brief summary
Spinal cord injury (SCI) results in permanent paralysis and significant disability. In addition, some spinal cord injured people experience postural hypotension, a large drop in blood pressure when assuming the upright position, associated with dizziness and fainting. For someone with SCI who is wheelchair dependent, fainting can have significant consequences such as further injury from falling out of the chair, reduced independence and limited vocational outcomes, thus poorer overall physical and psychological well-being.
In SCI, interruption of nervous communications, along with the loss of muscle pump in the legs, results in the impaired ability to maintain blood pressure on getting upright. Such persons have an abnormal pattern of blood pressure, whereby the blood pressure does not drop overnight, unlike the usual pattern. In some cases, there is even a higher blood pressure during the night than during the day – opposite to the normal pattern.
Higher night time blood pressure leads to increased night time urine production, leaving the body with relatively less circulating blood volume in the morning, at the time that one is about to get out of bed, further contributing to postural hypotension.
This study aims to examine the effects of treatment with captopril, a blood pressure lowering medication, at night, in a person with SCI who experiences symptoms of postural hypotension; we hypothesise that lowering night time blood pressure will reduce night time urine production, therefore increase blood pressure during the day, and reduce symptoms of postural hypotension, allowing the ability to stay upright during the day to carry out activities.
In this placebo controlled crossover study, participants will receive either the drug treatment or a placebo (dummy pill) for 8 weeks, and then switch to the other pill to determine if there is a difference in effects between the two. Each treatment period will be separated by two weeks where the participant is not on
either pill. Before and after each treatment, assessments include: measurements of blood pressure profile over 24 hours using an automatic portable monitor, recording urine volumes for 4 days, analysis of urine and blood samples.
Current treatment for such blood pressure disturbances and symptoms of low blood pressure are inadequate, and this study will help to determine whether this novel treatment is effective.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42826 0
Dr Christopher O'Callaghan
Address 42826 0
Department of Clinical Pharmacology
Harold Stokes Building Level 5
Austin Hospital
145 Studley Road
PO Box 5555
Heidelberg Vic 3084
Country 42826 0
Australia
Phone 42826 0
61 3 9496 5029
Fax 42826 0
61 3 9496 3221
Email 42826 0
christopher.o'[email protected]
Contact person for public queries
Name 42827 0
Melinda Millard
Address 42827 0
Victorian Spinal Cord Service
Harold Stokes Building Level 8
Austin Hospital
145 Studley Road
PO Box 5555
Heidelberg Vic 3084
Country 42827 0
Australia
Phone 42827 0
61 3 9496 5906
Fax 42827 0
Email 42827 0
[email protected]
Contact person for scientific queries
Name 42828 0
Min Yin Goh
Address 42828 0
Department of Clinical Pharmacology
Harold Stokes Building Level 5
Austin Hospital
145 Studley Road
PO Box 5555
Heidelberg Vic 3084
Country 42828 0
Australia
Phone 42828 0
61 3 9496 5029
Fax 42828 0
61 3 9496 3221
Email 42828 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
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