Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001583730
Ethics application status
Approved
Date submitted
18/11/2022
Date registered
22/12/2022
Date last updated
18/01/2023
Date data sharing statement initially provided
22/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the efficacy, acceptability and cost-effectiveness of a novel strategy based on a wearable blood pressure (BP) monitoring device (wrist-fitbit-type) for patients with high blood pressure plus a decision support strategy for general practitioners (GPs) on medication prescription for the treatment of hypertension. The NEXTGEN-BP randomised trial.
Scientific title
Transforming blood pressure control in primary care through a novel remote decision support strategy based on a wearable blood pressure monitoring device plus a decision support strategy for GPs on medication prescription: The NEXTGEN-BP randomised trial
Secondary ID [1] 308438 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 328237 0
Condition category
Condition code
Cardiovascular 325288 325288 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients in General Practice centres across Australia that have a clinical BP of greater than or equal to 140/90 millimetres of mercury (mmHg) and taking less than two BP drugs will be invited to participate in the study either via an invitation letter sent from the participating General Practice by the Study Coordinator (SC) with a nursing background or referred by the patient’s treating General Practitioner (GP). Patients who contact the SC or their GP will be asked to attend an appointment at the participating General Practice and will be consented and then assessed by the SC. Eligible participants will be randomised to the intervention or control arm. All consented patients will undergo study assessments by the SC at the first study visit.

Participants randomised to the intervention arm will receive the intervention. The intervention involves a strategy with two main components designed to address BP treatment inertia. Firstly, it includes a clinical decision-making tool based on hundreds of automated BP readings generated over time by a wrist-worn cuffless wearable BP device by the patient.
The clinical decision-making tool is a single number (percentage of BPs at target) provided by the study team to the GP practice through fax or email, prior to each patient visit. Patients will have continued access to their BP values shown on their device application (App) on their smartphone which synchronises with their device, which will allow for discussion with their GP and shared decision-making. This percentage of BPs at target will serve as a trigger to guide titration for GPs, aiming to achieve greater than 90 precent of BPs at target.
GPs will be provided with hard and soft copy access to the tool. They will be provided 1 hour training on using the tool by the study team upon site initiation which will occur two to four weeks prior to patient recruitment. GPs will be able to regularly liaise with the study team to clarify queries about the tool and online video will also be available for GPs to review at their own convenience.

The second component of the intervention includes two mandatory remote GP telehealth consultations (video or phone) at months 1 and 2 after enrolment into the study. The duration of the telehealth consultation is at the discretion of the GP. The study will not limit this interaction between GPs and patients but anticipate that it will be approximately 15 minutes in duration. Attendance rates will be monitored by the study team via appointment checklists.
At the first study visit at the General Practice, the SC will provide the wearable BP device to the trial participants who are randomised to the intervention group and they will be able to retain the device at the end of the trial. The SC will fit the patient with the device and provide instructions on how to use the device and to initialise with the device’s App on their mobile phone. Participants will be required to wear the device day and night for 12 months except when bathing, showering and swimming and at any in-person visits to the general practice as the SC taking the study measurements should not know that the patient is in the intervention arm.
Every month, the device’s mobile phone App will remind participants to initialise (calibrate) their wrist-worn BP device using the device App on their mobile phone and the BP cuff provided, to ensure accurate BP measurements are taken. Participants will also be asked to charge their device every week. One week prior to the scheduled GP telehealth consultations, the study team will prompt the participant to do the initialisation so that the single BP figure can be generated to provide to their GP. The App will not provide any information to participants such as alerts to book an appointment with their GP if their BP exceeds a safe limit or similar.

After 1 month and 2 months (two time points) of wearing the device, the single BP figure automatically generated by the device will be provided to the participant’s GP via fax or email by the study team. Based on this result, the GP will meet with the participant, via a telehealth appointment, to adjust the participant’s medication dose and provide an electronic script for the new dose to the patient. The GPs can use the following up-titration steps if BP at target is less than 90 percent and patient is not reporting symptoms of hypotension. If patient uses
* No medication, then start monotherapy
* 1 medication, add 1 medication
* 2 medications, double both doses (or add 1 medication)
* 3 medications, ensure at maximum dose or add spironolactone

For down titration steps based on symptoms, participants will be advised by their GP to switch to another drug.

The device’s App analytics will be used to analyse participant engagement with the App. The device analytics on the device dashboard monitored by the study team will be used to determine participants’ compliance with the intervention (continued use of wearable BP device).

At 3 months after the first in-person study visit, participants in both arms will be asked to attend an in-person appointment with the SC at the General Practice to measure heart rate and clinic BP; complete questionnaires on medication adherence, use of health services and engagement with study; to record any changes to medications and to collect information about the device as part of safety management.

At 12 months after the first in-person study visit, participants in both arms will be asked to attend an in-person appointment with the SC at the General Practice to measure the same variables collected at 3 months and also undertake some blood tests.
Intervention code [1] 324886 0
Prevention
Intervention code [2] 324888 0
Treatment: Devices
Comparator / control treatment
Participants randomised to the control arm will undergo usual care where their BP therapy will be initiated or uptitrated as per the treating GP’s discretion.
Control group
Active

Outcomes
Primary outcome [1] 333150 0
Difference in change in clinic systolic BP from baseline to 12 months (mmHg) using a validated supplied automatic, digital upper-arm cuff sphygmomanometer (Microlife WatchBP Office device).
Timepoint [1] 333150 0
At baseline and 12 months post randomisation (primary timepoint)
Secondary outcome [1] 415958 0
Efficacy: Net difference in change in clinic BP from baseline to 3 and 12 months using a validated supplied automatic, digital upper-arm cuff sphygmomanometer (Microlife WatchBP Office device).
Timepoint [1] 415958 0
At baseline, 3 months and 12 months post randomisation
Secondary outcome [2] 415959 0
Efficacy: Clinic BP control (percentage), achieving less than 140/90 mmHg at 3 and 12 months using a validated supplied automatic, digital upper-arm cuff sphygmomanometer (Microlife WatchBP Office device).
Timepoint [2] 415959 0
At 3 and 12 months post randomisation
Secondary outcome [3] 415960 0
Efficacy: Time at clinic BP target over 12 months using a validated supplied automatic, digital upper-arm cuff sphygmomanometer (Microlife WatchBP Office device).
Timepoint [3] 415960 0
At baseline and again at 12 months post randomisation.
Secondary outcome [4] 415961 0
Cost-effectiveness: Average total cost per patient achieving BP control, dollar per quality adjusted life year (QALY) from Medicare Benefit Schedule data access.
Timepoint [4] 415961 0
Cost data will be assessed at the conclusion of the study.
Secondary outcome [5] 415962 0
Engagement: Medication adherence using self-reported measures via the Adherence to Refills and Medications Scale (ARMS)-7 questionnaire and through Pharmaceutical Benefits Scheme prescription fills.
Timepoint [5] 415962 0
ARMS-7 questionnaire will be completed at the screening visit and 6 and 12 months post-randomisation. Prescription fill data from the Pharmaceutical Benefit Scheme will be assessed at the conclusion of the study.
Secondary outcome [6] 415963 0
Engagement: Visit attendance through Medicare Benefit Schedule data access
Timepoint [6] 415963 0
Medicare data will be assessed at the conclusion of the study
Secondary outcome [7] 415964 0
Engagement: Compliance with the intervention (continued use of wearable BP device) using the device analytics on the Aktiia dashboard monitored by the study team.
Timepoint [7] 415964 0
At months 3 and 12 post randomisation
Secondary outcome [8] 415965 0
Acceptability to patients via a process evaluation interview. These outcomes will be separately assessed via a semi-structured, one-on-one, face-to-face interview with a member of the research team.
Timepoint [8] 415965 0
At baseline, months 3 and 12 post randomisation
Secondary outcome [9] 415966 0
Engagement: Patient activation of the application, to assess patient engagement with the application, determined by accessing the device analytics to determine if participants have calibrated their device using the device application. The study team will prompt the participant to calibrate their device with the application.
Timepoint [9] 415966 0
1 week prior to the 1 month post- randomisation remote GP consultation and 1 week prior to the 2 months post- randomisation remote GP consultation
Secondary outcome [10] 415967 0
Safety: Incidence of adverse effects leading to treatment withdrawal. This data will be extracted from the general practice electronic health records system and collected via and adverse events case report form in the study database.
Examples of adverse events include:
* Symptomatic hypotension: Dizziness or any other symptom or event possibly related to hypotension
* Abnormal laboratory findings of sodium, potassium, uric acid, glucose, lipids, creatinine or eGFR
* Headache
* Peripheral oedema
* Any other symptom or laboratory abnormality that led to permanent discontinuation of medication.
Timepoint [10] 415967 0
At months 1, 2, 3 and 12 post randomisation
Secondary outcome [11] 417091 0
Acceptability to GPs via a process evaluation interview. These outcomes will be separately assessed via a semi-structured, one-on-one, face-to-face interview with a member of the research team.
Timepoint [11] 417091 0
At baseline, months 3 and 12 post randomisation.
Secondary outcome [12] 417092 0
BP medication titration: Uptitration or Down titration of BP medications as determined by the GP and will be extracted from the general practice electronic health records system.
Timepoint [12] 417092 0
At 1 month and 2 months post-randomisation at the remote GP consultation visits.

Eligibility
Key inclusion criteria
1. Provided signed or electronic consent to participate in the trial
2. Males and females
3. Aged greater than or equal to 18 years
4. Average clinic attended seated mean BP greater than or equal to 140 and/or 90 mmHg, treated or untreated; or documented high BP in the last 3 months (clinic or home)
5. Willing to self-monitor BP
6. Own a compatible smartphone (iPhones running iOS 11 or newer and Android devices running 8.0 or newer) and ability to use it;
7. Access to an internet connection to allow GP telehealth consultations
8. The patient is deemed eligible for the treatment protocol by the GP.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Taking 3 or more BP-lowering drugs.
2. Participant’s responsible primary care or other responsible physician deems not suitable for remote management – including use of wearable BP device, reporting of symptoms, and following electronic script-based titration steps.
3. Unable to complete trial procedures including cuffless BP monitoring.
4. Planned overseas travel in the first 30 days of joining the trial and if planning to travel for longer than 6 months during the trial period.
5. GP deems participant unsuitable to switch current antihypertensive therapy or a definite indication for combination therapy.
6. Pregnant or had a positive pregnancy test or unwilling to undertake a pregnancy test during the trial, or breastfeeding.
7. Of childbearing age and not using an acceptable method of contraception. Acceptable methods of birth control include hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (e.g. condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization. Contraception should be used for at least 1 month before the screening visit and until the end of trial participation. Note: Females who are not at risk for pregnancy (i.e. in non-heterosexual relationships, single or who otherwise do not have male partners) are still eligible for the trial if they do not use contraception.
8. Evidence of secondary cause of hypertension e.g. renal artery stenosis
9. History of significant renal impairment (estimated glomerular filtration rate [eGFR] less than 50 ml/min/1.73 m squared), raised serum potassium (above lab normal limit).
10. Participation in a concurrent clinical trial of an investigational medicinal product. (Participants in observational, natural history and/or epidemiological studies not involving an intervention are eligible.)
11. Concomitant illness, physical impairment or mental condition which in the opinion of the trial team/primary care physician could interfere with the conduct of the trial including outcome assessments.
12. Inability or unwillingness to provide written informed consent.

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 using a web-based platform.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Not Applicable
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size of 600 participants will provide greater than 90% power to detect a clinic systolic BP (SBP) difference of 5 mmHg between groups based on the following assumptions: a common standard deviation of 17mmHg, an alpha of 0.05 using a two-sided two-sample equal-variance t-test, and a drop-out rate of 15%. This sample size will also allow us to detect a difference of approximately 15% in time at BP target (defined as % of time at target BP) with a power of 89% and at an alpha adjusted for multiplicity at 0.025.

All analyses will be performed on an intention-to-treat basis. Baseline characteristics by the group will be compared using descriptive analyses. The primary outcome of difference in change in clinic SBP from baseline to 12 months will be analysed by a hierarchical linear model with fixed effects for treatment group, time (clinic visit), treatment by time (clinic visit) interaction, baseline clinic SBP, and allowing for a random-effect at site level. Other continuous outcomes of difference in change in BP will also be analysed with the modelling approach used for the primary outcome. The percentage of participants achieving target BP at months 3 and 12 will be summarised descriptively as well as analysed using a hierarchical log-binomial model with the treatment group as a fixed effect and the trial site as a random effect. Other binary outcomes of efficacy and safety will be analysed as the percentage of participants achieving target BP. A detailed statistical analysis plan (SAP) will be developed and made publicly available prior to the final data-lock.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
28/02/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
600
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC

Funding & Sponsors
Funding source category [1] 312685 0
Government body
Name [1] 312685 0
Australian Government Department of Health and Aged Care, Medical Research Future Fund (MRFF)
Country [1] 312685 0
Australia
Primary sponsor type
Other
Name
The George Institute for Global Health
Address
Level 5, 1 King St
Newtown
NSW 2042 Australia
Country
Australia
Secondary sponsor category [1] 314296 0
None
Name [1] 314296 0
Address [1] 314296 0
Country [1] 314296 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311987 0
University of New South Wales Human Research Ethics Committee
Ethics committee address [1] 311987 0
UNSW Sydney
High St
Kensington NSW 2052
Australia
Ethics committee country [1] 311987 0
Australia
Date submitted for ethics approval [1] 311987 0
05/09/2022
Approval date [1] 311987 0
01/11/2022
Ethics approval number [1] 311987 0
HC220617

Summary
Brief summary
The primary aim is to assess in adults with hypertension, the efficacy of a remote wearable BP-based care strategy to reduce BP in primary care over 12 months, compared to usual care.
The secondary aims are to determine if this remote wearable BP-based care strategy:
* is acceptable to patients and GPs
* is cost-effective
* improves medication adherence
* improves patient engagement,
* is safe, compared to usual care

Hypothesis: The remote wearable BP-based care strategy will be superior to usual care in terms of efficacy in BP reduction, acceptability to patients and GPs, and cost-effectiveness.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123074 0
Prof Aletta Schutte
Address 123074 0
The George Institute for Global Health
Level 5, 1 King St
Newtown
NSW 2042 Australia
Country 123074 0
Australia
Phone 123074 0
+61 2 8052 4300
Fax 123074 0
Email 123074 0
[email protected]
Contact person for public queries
Name 123075 0
Prof Aletta Schutte
Address 123075 0
The George Institute for Global Health
Level 5, 1 King St
Newtown
NSW 2042 Australia
Country 123075 0
Australia
Phone 123075 0
+61 2 8052 4300
Fax 123075 0
Email 123075 0
[email protected]
Contact person for scientific queries
Name 123076 0
Prof Aletta Schutte
Address 123076 0
The George Institute for Global Health
Level 5, 1 King St
Newtown
NSW 2042 Australia
Country 123076 0
Australia
Phone 123076 0
+61 2 8052 4300
Fax 123076 0
Email 123076 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
Medical data pertaining to an individual will not be made public. Only aggregate summary data will be published.


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
SourceTitleYear of PublicationDOI
EmbaseTransforming blood pressure control in primary care through a novel remote decision support strategy based on wearable blood pressure monitoring: The NEXTGEN-BP randomized trial protocol.2023https://dx.doi.org/10.1016/j.ahj.2023.07.005
N.B. These documents automatically identified may not have been verified by the study sponsor.