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Trial registered on ANZCTR


Registration number
ACTRN12618001625268
Ethics application status
Approved
Date submitted
3/07/2018
Date registered
3/10/2018
Date last updated
3/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Tolerability of different doses of blood pressure lowering Polypill
Scientific title
Tolerability and blood pressure lowering of two different dose antihypertensive Polypills, compared to conventional dual combination
Secondary ID [1] 295393 0
Nil
Universal Trial Number (UTN)
U1111-1216-5921
Trial acronym
PDS (Polypill Dose Study)
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Systemic hypertension 308623 0
Complicated hypertension 308624 0
Condition category
Condition code
Cardiovascular 307570 307570 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Irbesartan 150mg once daily orally
Hydrochlorothiazide 12.5mg once daily orally
9 weeks

Phase A:
Amlodipine 0.5 mg once daily orally
Hydrochlorothiazide 2 mg once daily orally
Spironolactone 2 mg once daily orally
Perindopril 0.75 mg once daily orally
Bisoprolol 0.2 mg once daily orally
for 9 weeks

Phase B:
Amlodipine 1 mg once daily orally
Hydrochlorothiazide 4 mg once daily orally
Spironolactone 4 mg once daily orally
Perindopril 1.5 mg once daily orally
Bisoprolol 0.4 mg once daily orally
each for 9 weeks

Patients will be treated in each Phase in randomised order.
Tablet counts will be undertaken of returns.
No washout is planned, given that the analysed BP and other measurements will not begin until 6 weeks into each phase.


Intervention code [1] 301706 0
Prevention
Comparator / control treatment
We aim in stable hypertensive patients to carefully quantify and compare blood pressure, tolerability and all adverse effects on 2 different dose very low dose multiple combination antihypertensive regimens, compared to moderate dose simple combination regimen. All patients will receive the 3 treatments, in randomised sequence.


The comparator/reference treatment will be the Irbesartan 150mg + Hydrochlorothiazide 12.5mg once daily Phase

Control group
Active

Outcomes
Primary outcome [1] 306550 0
Adverse events
eg faintness, syncope, rash, nausea

Any intolerance and all specific adverse symptoms will be evaluated every 3 weeks, in the clinic and by telephone.
All new or increased symptoms will be documented and evaluated as possible adverse events.


Timepoint [1] 306550 0
3 Phases, each of 9 weeks duration

Baseline (commencement of Phase 1 of drug treatment)
9 weeks post-commencement = beginning of Phase 2
18 weeks = beginning of Phase 3
Finish at 27 weeks


Secondary outcome [1] 348847 0
Mean blood pressure (clinic, ambulatory)

Timepoint [1] 348847 0
At baseline and at 6 & 9 weeks in each of the 3 Phases, clinic and 24 hour ambulatory BP & HR
Secondary outcome [2] 352253 0
Mean heart rate (ECG, clinic, ambulatory)
Timepoint [2] 352253 0
At baseline and at 6 & 9 weeks in each of the 3 Phases, ECG, clinic and 24 hour ambulatory HR

Eligibility
Key inclusion criteria
To qualify, patients must have:

ECG changes typical of hypertension: T-wave flattening or inversion, and/or voltage LVH and/or left axis deviation.

Previous SBP between 150 and 200 mm Hg systolic

Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No clinical cardiovascular events (angina, acute coronary syndrome/AMI, cardiac failure, TIA or stroke) in the previous 1 year

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
Sealed Polypill capsule
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation, using this website/link:
http://numbergenerator.org/20randomnumbers#!numbers=20&low=1&high=6&unique=true&start=false
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
t-test
ANOVA

As this is our first study with different doses of Polypill, the variance and comparability in our patients is unknown. A previous similar study which used placebo as a comparator recruited 20 participants. (Chow CK, Thakar J, Bennett A, et al. Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review. Lancet 2017;389:1035-42.)
An interim analysis will be undertaken and if findings are unconvincing, recruitment will be continued.



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 in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 299984 0
Charities/Societies/Foundations
Name [1] 299984 0
Beyond Community & Health Foundation
Address [1] 299984 0
Beyond Community & Health Foundation
2/62 Archibald St
Willagee WA 6156
Country [1] 299984 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Beyond Community & Health Foundation
Address
Beyond Community & Health Foundation
2/62 Archibald St
Willagee WA 6156
Country
Australia
Secondary sponsor category [1] 299365 0
University
Name [1] 299365 0
University of Western Australia
Address [1] 299365 0
35 Stirling Hwy
Crawley WA 6009
Country [1] 299365 0
Australia
Other collaborator category [1] 280216 0
Individual
Name [1] 280216 0
Professor Jennifer H Martin
Address [1] 280216 0
School of Medicine & Public Health
University of Newcastle
University Drive
Callaghan NSW 2308
Country [1] 280216 0
Australia
Other collaborator category [2] 280369 0
Individual
Name [2] 280369 0
Professor Hans Stampfer
Address [2] 280369 0
School of Psychiatry and Clinical Neurosciences
University of Western Australia
35 Stirling Hwy
Nedlands WA 6009
Country [2] 280369 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300840 0
St John of God Health Care HREC
Ethics committee address [1] 300840 0
St John of God Health Care, Salvado Rd, Subiaco WA 6008
Ethics committee country [1] 300840 0
Australia
Date submitted for ethics approval [1] 300840 0
06/12/2017
Approval date [1] 300840 0
13/12/2017
Ethics approval number [1] 300840 0
Ref 1077

Summary
Brief summary
Very low dose multiple combination antihypertensive pharmacotherapy can improve risk/benefit compared to (conventional) moderate dose simple combination therapy because the multiple actions lower blood pressure (BP) more efficiently and the lower doses cause fewer adverse effects.

We aim in stable hypertensive patients to carefully quantify and compare blood pressure, tolerability and all adverse effects on 2 different dose very low dose multiple combination antihypertensive regimens, compared to moderate dose simple combination regimen. All patients will receive the 3 treatments, in randomised sequence.

All patient file data will be entered into a database by a Research Assistant. All data recorded will be de-identified. All patient data recorded will remain confidential, kept secure in a computer database on a computer locked in the research office. The Principal Investigator will not discuss data collected with the patients during the study.

Statistical variance in Polypill treatments like these is not established. This is a pilot trial. The statistical analysis will be undertaken on Excel under the oversight of Professor Hans Stampfer. Should either efficacy or safety appear encouraging, we will seek grant support to extend the study to 3 sites, to recruit sufficient numbers to best establish risk/benefit of the Polypill regimen.

A consultation after the study will resolve recommendations for ongoing treatment.

Trial website
Nil
Trial related presentations / publications


Public notes
Basis and discussion for the low dosing used in the current study:

Dimmitt S, Stampfer H, Martin JH.
When less is more – efficacy with less toxicity at the ED50.
British J Clin Pharmacol 2017 83: 1365-8.

Contacts
Principal investigator
Name 84990 0
Prof Simon B Dimmitt
Address 84990 0
Beyond Community & Health Foundation
2/62 Archibald St
Willagee WA 6156
Country 84990 0
Australia
Phone 84990 0
+61419042914
Fax 84990 0
+618 9331 7299
Email 84990 0
simondimmitt@gmail.com
Contact person for public queries
Name 84991 0
Prof Simon B Dimmitt
Address 84991 0
Beyond Community & Health Foundation
2/62 Archibald St
Willagee WA 6156
Country 84991 0
Australia
Phone 84991 0
+618 9331 7233
Fax 84991 0
+618 9331 7299
Email 84991 0
simondimmitt@gmail.com
Contact person for scientific queries
Name 84992 0
Prof Simon B Dimmitt
Address 84992 0
Beyond Community & Health Foundation
2/62 Archibald St
Willagee WA 6156
Country 84992 0
Australia
Phone 84992 0
+618 9331 7233
Fax 84992 0
+618 9331 7299
Email 84992 0
simondimmitt@gmail.com

No information has been provided regarding IPD availability
Summary results
No Results