Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001057673
Ethics application status
Approved
Date submitted
4/04/2014
Date registered
3/10/2014
Date last updated
6/08/2019
Date data sharing statement initially provided
6/08/2019
Date results information initially provided
6/08/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
QUADPILL Pilot Feasibility Study: Can an ultra low-dose 'hypertension polypill' provide better blood pressure control with fewer side effects?
Scientific title
Can an ultra low-dose 'hypertension polypill' provide better blood pressure control with fewer side effects? Feasibility study.
Secondary ID [1] 283924 0
nil
Universal Trial Number (UTN)
U1111-1152-2426
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 290927 0
Condition category
Condition code
Cardiovascular 291282 291282 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Quadpill will be a single gelatin capsule containing 1/4 standard doses of 4 common blood pressure lowering medications (Irbesartan 37.5 mg, Amlodipine 1.25 mg, Atenolol 12.5 mg and Hydrochlorothiazide 6.25 mg). Participants are randomly allocated to intervention or control therapy during the first cross-over period. Participants allocated to intervention will take one Quadpill orally once daily for 4 weeks, followed by a 2 week wash-out period and then a 4 week period where they will receive an identical looking tablet that contains placebo. Participants allocated to control first will receive the above in reverse.
There are no additional strategies to improve adherence to the intervention. Adherence will be monitored by drug tablet return and self-report.
Intervention code [1] 288613 0
Treatment: Drugs
Comparator / control treatment
The trial drug will be evaluated against Placebo. However due to the cross over design all participants will receive intervention (Quadpill) and Control (Placebo) at different time-points during the study. Placebo will appear identical to the intervention and be a single gelatin capsule containing sugar pills instead of active ingredients.
Control group
Placebo

Outcomes
Primary outcome [1] 291281 0
Systolic blood pressure: Patients will be rested in the seated position for 5 minutes, an appropriate cuff size will be selected, the cuff wrapped around the upper arm and the bladder centred over the brachial artery and 3 measurements of blood pressure will be recorded using an Omron automated digital blood pressure monitor. The monitor will be validated every 6 months and serviced at least once every 12 months according to the Heart Foundation recommendations
Timepoint [1] 291281 0
After 4 weeks of active treatment
Secondary outcome [1] 306417 0
Percentage achieving blood pressure control <140/90 using an Omron automated digital blood pressure monitor
Timepoint [1] 306417 0
Assessed at 4 weeks and at 10 weeks due to crossover design. Percentage achieving control after 4 weeks of active treatment.
Secondary outcome [2] 310377 0
Safety profile - through monitoring of blood and urine test (Electrolytes, Renal function, liver function, blood sugar); clinical follow-up using standardised questionnaires asking about side effects/ adverse effects. The questionnaire has been designed to evaluate side effects/ adverse effects that can be associated with the trial medications. For example participants will be asked if they have suffered any side effects, dizziness, blurred vision, syncope/ collapse, chest pain/ angina, shortness of breath, cough, wheeze, pedal edema (ankle swelling), skin rash, itching and other. If other they are asked to specify in a free text field. In addition blood and urine tests will be monitored as described above and any abnormalities recorded.
Timepoint [2] 310377 0
Safety is assess throughout both active and control treatments at 4 weeks and 10 weeks
Secondary outcome [3] 310378 0
Acceptability - will be assessed using standardised questionnaires. The questionnaire is not a named questionnaire but the questionnaire has been designed for this trial and uses questions from other polypill trials on acceptability.
Timepoint [3] 310378 0
At 10 weeks
Secondary outcome [4] 310379 0
Adhererence is assessed on pill counts and self-report e.g. have you missed any doses in the last 7 days.
Timepoint [4] 310379 0
Pill counts and self-reported medical adherence are assessed at 4 weeks and 10 weeks.
Secondary outcome [5] 310704 0
Mean 24 hour ambulatory blood pressure
Timepoint [5] 310704 0
Measured at 4 weeks and at 10 weeks.

Eligibility
Key inclusion criteria
1) Adults aged 18 years and over.
2) Systolic BP>140mmHg or diastolic BP> 90 mmHg on 2 readings on separate days.
3) Treatment Naive. (Not on medical treatment for hypertension).
4) No definite contraindications to quadpill medications, at the doses used in this trial.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) The responsible clinician feels change in current therapy will place the patient at risk.
2) Severe or Accelerated Hypertension.
3) Pregnancy, Planning Pregnancy in 3 months, Lactating mothers
4) Inability to provide informed consent,
5) Medical illness with anticipated life expectancy < 3 months

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)
Potential participants will be identified from the community through advertising and through general practices. We will use advertising in community media (e.g. local newspapers), community radio or posters/ flyers. We will also identify potential participants by approaching general practices.
Randomisation will be 1:1 and conducted through a central, computer-based randomisation service. Treatment allocation will be blinded to both study staff and participants. Patients will be randomised to hypertension polypill i.e. 'Quadpill' or placebo in treatment period 1 and then to the opposite, ie control or Quadpill in the treatment period 2.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using 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
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
For a crossover trial a sample size of 50 patients at p is equal to 0.05 would have 90% power to detect a blood pressure difference of 12 mmHg between the intervention and control assuming an SD of 15mmHg and a SD of the within patient difference of 12 mmHg. This sample size takes into account the possibility of a 10% loss to follow-up.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/09/2014
Actual
1/09/2014
Date of last participant enrolment
Anticipated
1/06/2015
Actual
15/10/2015
Date of last data collection
Anticipated
Actual
29/12/2015
Sample size
Target
50
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 288564 0
Charities/Societies/Foundations
Name [1] 288564 0
Heart Foundation - Vanguard Grant 2013 App 100227
Country [1] 288564 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
The George Institute for Global Health
Address
Level 10, King George V Building, Missenden Road, Camperdown. NSW. 2050
Country
Australia
Secondary sponsor category [1] 287278 0
University
Name [1] 287278 0
The University of Sydney
Address [1] 287278 0
The University of Sydney,
NSW. 2006.
Country [1] 287278 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290427 0
The University of Sydney - Human Ethics Research Committee
Ethics committee address [1] 290427 0
Level 2, Margaret Telfer Building K07,
NSW. 2006.
Australia
Ethics committee country [1] 290427 0
Australia
Date submitted for ethics approval [1] 290427 0
13/01/2014
Approval date [1] 290427 0
08/04/2014
Ethics approval number [1] 290427 0
2014/108

Summary
Brief summary
To establish the feasibility, patient acceptability, effect on blood pressure and thereby overall potential of a simplified treatment strategy with 'hypertension polypill', which includes four common blood pressure lowering medications each at 1/4 strength dose.
This pilot study will be double blind randomised placebo- controlled crossover trial of 50 patients with established hypertension not on any medical therapy. Subjects will be randomised into two arms - intervention (Quadpill) and control (placebo)- for a period of four weeks. They will undergo office blood pressure as well as 24 hour ambulatory BP assessment at baseline and in 4th week in addition to safety monitoring blood tests. Thereafter there will be a 2 week washout phase prior to crossing over to opposite arm of the study. The patients will undergo another baseline blood and 24 hour ambulatory BP assessment. The study will conclude at 10 week with repeat measurements. The outcomes assessed will be change in the mean blood pressure, safety, tolerability and acceptability.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 45642 0
Prof Clara Chow
Address 45642 0
Westmead Applied Research Centre Faculty of Medicine and Health
The University of Sydney/Westmead Hospital
Westmead NSW 2145
Country 45642 0
Australia
Phone 45642 0
+61 2 8890 3125
Fax 45642 0
+61 2 8890 8323
Email 45642 0
[email protected]
Contact person for public queries
Name 45643 0
Dr Jay Thakkar
Address 45643 0
Level 2, Cardiology Department,
Westmead Hospital.
Cnr Darcy road - Hawkesbury road.
Westmead. NSW. 2145
Country 45643 0
Australia
Phone 45643 0
+61 2 9845 5555
Fax 45643 0
Email 45643 0
[email protected]
Contact person for scientific queries
Name 45644 0
Prof Clara Chow
Address 45644 0
Westmead Applied Research Centre Faculty of Medicine and Health
The University of Sydney/Westmead Hospital
Westmead NSW 2145
Country 45644 0
Australia
Phone 45644 0
+61 2 8890 3125
Fax 45644 0
+61 2 8890 8323
Email 45644 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
Not permitted under ethics approval


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23312Statistical analysis plan   

Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes February 9, 2017 365646-(Uploaded-31-07-2019-10-20-58)-Journal results publication.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseQuarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review.2017https://dx.doi.org/10.1016/S0140-6736%2817%2930260-X
N.B. These documents automatically identified may not have been verified by the study sponsor.