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Trial registered on ANZCTR


Registration number
ACTRN12618001110279
Ethics application status
Approved
Date submitted
22/06/2018
Date registered
4/07/2018
Date last updated
9/01/2019
Date data sharing statement initially provided
9/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Identification of adults with true high blood pressure resistant to drugs and its relationship with breath pauses during sleep.
Scientific title
The prevalence of true resistant hypertension in Dunedin based adults with resistant hypertension and the association between true resistant hypertension and obstructive sleep apnoea risk.
Secondary ID [1] 295142 0
None
Universal Trial Number (UTN)
U1111-1215-4535
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Resistant hypertension 308240 0
Obstructive sleep apnoea 308241 0
Condition category
Condition code
Cardiovascular 307266 307266 0 0
Hypertension
Respiratory 307267 307267 0 0
Sleep apnoea

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This study is an observational study which aims to: 1) identify individuals with true resistant hypertension (TRHT) in a population of Dunedin based adults 60 years and younger, with resistant hypertension (RHT) as defined under the current guidelines (2017) of the American Heart Association and American College of Cardiology; 2) investigate the association between TRHT and high risk of obstructive sleep apnoea (OSA) in the sub group of individuals with TRHT.
Dunedin based adults, 60 years or younger, who meet the criteria for RHT (are on three or more pharmacological agents of different classes, including a diuretic), have been identified from the Ministry of Health Pharmaceutical Collection Warehouse (PCW) database.

Following a briefing by researchers about the study at a scheduled meeting of the local General Practitioners Association, researchers will gain agreement from General Practitioners to distribute a letter to patients. A letter of invitation to participate in the study will be co-signed by Dr. Skinner and Associate Professor Wilkins. Letters will then be distributed to General Practitioners, who will be asked to forward copies to their patients identified from the PCW database.

Step I – Initial recruitment
Potential participants will be invited to contact Dr Skinner with enquiries and to indicate their interest in participating in the study. The Principal investigator (PI), the PhD candidate, will provide each participant with an appointment time for the initial assessment where written informed consent will be obtained first. The session will be at the School of Physiotherapy.

Step II – Assessment and measurements
Appointment 1:
The PI will obtain the participant’s demographic data (age; gender; ethnicity); general health and habits, physical activity level, quality of life (SF-36) and OSA risk (ESS), using self-administered questionnaires. Participants will use a tablet computer to complete this section which will take approximately 20 minutes. Data will then be downloaded onto the study database (MS Excel).

The PI will then take the participant’s resting blood pressure (office blood pressure – (BP)), heart rate, and peripheral saturation using standardised, calibrated equipment (NT1A Pulse oximeter, New Tech, Hamburg, Germany and Omron automatic digital blood pressure monitor, HEM 7322, Netherlands) and in accordance with the ACC/AHA 2017 guidelines. Next, the PI will take the anthropometric (body weight, height and circumferences of neck, waist, hip,) measurements of the participant using standard guidelines and equipment; electronic weighing scale (kg) and stadiometer (cm), measuring tape (scale in cm); with two decimal point accuracy. The equipment will be calibrated as required. This section of the procedure will take about 15 minutes. The variables, body mass index (BMI) and waist to hip ratio will be calculated using simple formulas on MS Excel.

The subset with RHT who also score above or equal 9 on the Epworth Sleepiness Scale (ESS) will be identified as ‘at risk for OSA’, and will be fitted with 24h ambulatory blood pressure monitor on the non-dominant upper arm, at the Cardiology Research Laboratory, on 9th floor in Dunedin Hospital. The participant will be advised to undertake daily activities/sleep as usual over the next 24 hours.

Appointment 2:
On the following day, the device will be removed at the same setting, the Cardiology Research Laboratory, and data downloaded to confirm TRHT or not. Where THRT is confirmed the participant will have an echocardiogram to confirm baseline left ventricular function (results to be interpreted by co-investigator cardiologist).

After the echocardiogram, the PI will conduct a Six Minute Walk Test (6MWT) following the standardised test and safety procedures. Then an activity monitor (ActiGraph GT3XPB, Pensacola, Florida) will be calibrated and placed on the non-dominant wrist to be worn for seven days/nights to determine the participant’s true levels of functional activity during the day and during sleep. The participants will select the most convenient way to return the Activitrax monitor, either in person or by post. Data will be downloaded and analysed for activity levels, and sleep parameters, by the PI. Objective measurements of daytime activity (step count, time in low/moderate/vigorous physical activity, sedentary time and sleep, including total sleep time, awakenings, average awakenings, sleep efficiency, sleep onset, latency and wake after sleep onset) will be derived from the Actigraph calculator for the period.

The PI who will then determine the correlation between Epworth Sleepiness Scale score and sleep fragmentation and subsequently identify those with high risk of OSA in the subset with TRHT.

Note: Participants not found to have TRHT will meet with the co-investigator (Primary Supervisor) to discuss the outcomes and will be advised to visit their GP to discuss the report on findings for 24hABPM, risk of OSA (obtained from the questionnaire, ESS above or equal to 9), and self-reported physical activity level). The participants with objective signs of OSA scored from the data downloaded from the activity monitor but not with TRHT will be referred by the co-investigator cardiologist, to the physician at the Sleep Clinic for further sleep analysis.

Individuals who have TRHT and high risk of OSA will be invited to participate in a second study: a feasibility study to investigate the outcomes of a supervised physical activity programme on blood pressure levels.



Intervention code [1] 301478 0
Diagnosis / Prognosis
Intervention code [2] 301479 0
Early Detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306217 0
The primary outcome is the prevalence of TRHT. TRHT will be assessed using 24h ambulatory blood pressure monitoring, in Dunedin based population of adults with resistant hypertension
Timepoint [1] 306217 0
24h from the appointment 1
Primary outcome [2] 306451 0
The positive association between participants with TRHT and the high risk of OSA
Timepoint [2] 306451 0
One week following appointment 2
Secondary outcome [1] 347902 0
Correlation between increased Epworth Sleepiness Scale score and sleep fragmentation using the sleep/wake data downloaded by the actigraphy monitoring .
Timepoint [1] 347902 0
One week from the appointment 2
Secondary outcome [2] 348591 0
cardio respiratory fitness will be gauged by the six minute walk test, using a 30 meter indoor walking track, of the population with TRHT and high risk of OSA.

Timepoint [2] 348591 0
One week from the appointment 2
Secondary outcome [3] 348769 0
Physical activity level will be measured from activity level captured over seven days and downloaded from the Actigraph monitor; daily amounts, frequency and levels of activity will be determined for each of seven days, of the population with TRHT and high risk of OSA. (This is a composite secondary outcome)
Timepoint [3] 348769 0
One week from the appointment 2
Secondary outcome [4] 348770 0
Structural and functional features of the heart - size and shape of the heart pumping capacity, and the location and extent of any tissue damage and estimates of heart function (cardiac output and ejection fraction), will be described from the results of two dimensional electrocardiography, of the population with TRHT and high risk of OSA. (This is a composite secondary outcome)
Timepoint [4] 348770 0
On the day of appointment 2

Eligibility
Key inclusion criteria
Age: 18-60 years inclusive
Gender: all
Able to communicate/follow instructions in English
Based in Dunedin region
Diagnosed with hypertension
Prescribed three of more antihypertensive medications including a diuretic (RHT Definition).
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Diagnosed with hypertension prescribed two or less antihypertensive medications
Adults above the age of 60 years
Diagnosed/known renal disease
Females who are pregnant

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
A statistician was consulted to confirm the calculation of the sample size based on the population with RHT in Dunedin region (559). Thus, the sample size is n=83, with 95% confidence level and 10% margin of error. The recruitment target is set at n=100 and with the dropout rate of up to 20%, the estimated sample size (n=83) is expected to be able to be fulfilled.

The cohort with true resistant hypertension and high risk of OSA is unknown for the Dunedin based population with RHT. An 18% response rate will be sufficient to achieve the target sample size (n=100) for the study.

Simple statistics (mean, standard deviation, range) will be used to describe the demographic data and the measurements (anthropometry, blood pressure, sleep, activity, cardiac parameters) of the population with RHT in Dunedin region and in the subpopulation with TRHT and high risk of OSA. The data for anthropometrics, blood pressure, activity and cardiac parameters will be compared with accepted international guidelines, and questionnaires will be interpreted using standard descriptors.

The relationship between the anthropometry parameters, blood pressure, ESS score, cardiorespiratory fitness, and activity and sleep levels with TRHT will be determined using regression analysis.

The statistical package for social sciences (SPSS) version 25.0 or above for Windows (IBM SPSS version 25.0 or above), NY, USA will be used for the data analysis.





Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 10538 0
New Zealand
State/province [1] 10538 0
Dunedin/ Otago

Funding & Sponsors
Funding source category [1] 299733 0
University
Name [1] 299733 0
School of physiotherapy, University of Otago
Address [1] 299733 0
325,Great King Street, Dunedin North (9016)
Country [1] 299733 0
New Zealand
Primary sponsor type
Individual
Name
Dr. Margot Skinner
Address
School of Physiotherapy, University of Otago,
325, Great King Street,
Dunedin North. 9016
Country
New Zealand
Secondary sponsor category [1] 299068 0
Individual
Name [1] 299068 0
Suranga Dassanayake
Address [1] 299068 0
School of Physiotherapy, University of Otago,
325, Great King Street,
Dunedin North 9016
Country [1] 299068 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300623 0
Health and Disability Ethics Commitee
Ethics committee address [1] 300623 0
Postal address:
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 300623 0
New Zealand
Date submitted for ethics approval [1] 300623 0
13/07/2018
Approval date [1] 300623 0
10/09/2018
Ethics approval number [1] 300623 0
18/CEN/141

Summary
Brief summary
High blood pressure (BP) or hypertension (HT) is a worldwide problem. BP which is difficult to maintain using three or more BP medications is defined as resistant hypertension (RHT). The exact global prevalence of RHT is unknown but it has been estimated to be 20-30% of the population with HT. 24 hour BP monitoring (24h Ambulatory Blood Pressure Monitoring - 24ABPM) is recommended to exclude the potential for a false reading of BP in the clinical settings and thereby to diagnose true RHT (TRHT). Cardiovascular disease is the greatest cause of morbidity and mortality in New Zealand and the prevalence of HT in the adult population is over 30%, with ethnic disparities. The most common form of sleep disordered breathing, obstructive sleep apnoea (OSA), has a strong relationship with uncontrolled RHT and research indicates that both conditions enhance each other.
The hypotheses of the designed study are; 1) In Dunedin based individuals aged 60 years and below, diagnosed with RHT, 24h ABPM will identify a subgroup with TRHT; 2) There is correlation between Epworth Sleepiness Scale (ESS) score and levels of sleep fragmentation in the subgroup of individuals with TRHT; 3)There is an association between TRHT and high risk of OSA, in the subgroup of individuals.

The population has been identified from the Ministry of Health Pharmaceutical Collection Warehouse. Consenting adults will complete health, OSA risk and activity questionnaires. The subset with RHT and OSA risk will have 24h ABPM to confirm TRHT, anthropometric measurements, cardiorespiratory fitness, echocardiogram, sleep and activity monitoring for seven days and nights. Sleep outcomes and ESS score will be used to confirm the level of risk of OSA.

The aims of the study are to: 1) identify individuals with TRHT in a population of Dunedin based adults 60 years and younger, with RHT as defined under the current guidelines (2017) of the American Heart Association and American College of Cardiology; 2) investigate the association between TRHT and high risk of OSA in the sub group of individuals with TRHT.

The objectives are; to determine the prevalence of TRHT measured by 24h ABPM in Dunedin based individuals with RHT; to investigate the relationship between ESS scores and sleep fragmentation in the Dunedin based individuals identified TRHT; to investigate the association between TRHT and high risk of OSA, in the Dunedin based individuals.

The outcomes of the study will be; The prevalence of TRHT in a population with RHT and its association with high risk of OSA and the correlation between increased ESS score and sleep fragmentation in the subset with TRHT.

The investigators will adhere to the new guideline for HT and include only those with TRHT which leads to creating a new knowledge dimension. The findings have potential to change the direction of research in the area, open the topic of TRHT to more debate and support modified guidelines for physicians and physiotherapists in managing.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84250 0
Mr Suranga Dassanayake
Address 84250 0
School of Physiotherapy, University of Otago,
325, Great King Street
Dunedin North 9016.
Country 84250 0
New Zealand
Phone 84250 0
+64 224976151
Fax 84250 0
Email 84250 0
suranga.dassanayake@postgrad.otago.ac.nz
Contact person for public queries
Name 84251 0
Mr Suranga Dassanayake
Address 84251 0
School of Physiotherapy, University of Otago,
325, Great King Street
Dunedin North 9016.
Country 84251 0
New Zealand
Phone 84251 0
+64 224976151
Fax 84251 0
Email 84251 0
suranga.dassanayake@postgrad.otago.ac.nz
Contact person for scientific queries
Name 84252 0
Dr Margot Skinner
Address 84252 0
School of Physiotherapy, University of Otago,
325, Great King Street
Dunedin North 9016.
Country 84252 0
New Zealand
Phone 84252 0
+64 34797466
Fax 84252 0
Email 84252 0
margot.skinner@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The individual data for the study will be available but not will be shared with any other research or with another party. Only the study investegators will be able to access data. The data will be kept for 4 years according to the regulations.
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
Attachments/websites
Type [1] 972 0
Ethical approval
URL/details/comments [1] 972 0
Summary results
No Results