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Trial registered on ANZCTR


Registration number
ACTRN12606000067572
Ethics application status
Approved
Date submitted
15/02/2006
Date registered
16/02/2006
Date last updated
3/06/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Improving Adherence using Combination Therapy
Scientific title
Does a polypill improve cardiovascular guideline implementation in primary care in those at high risk of cardiovascular disease
Secondary ID [1] 252001 0
Nil
Universal Trial Number (UTN)
Trial acronym
IMPACT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
High risk of cardiovascular disease 1031 0
Condition category
Condition code
Cardiovascular 1105 1105 0 0
Normal development and function of the cardiovascular system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Polypill-based care for 12 months until the last participant has been randomised. In the polypill arm, one polypill (a capsule) is to be taken orally, once a day. 2 versions of polypill (choice of which at the discretion of the General Practitioner): Version 1: One capsule contains aspirin 75mg, simvastatin 40mg, lisinopril 10mg and atenolol 50mg; Version 2: One capsule contains aspirin 75mg, simvastatin 40mg, lisinopril 10mg and hydrochlorothiazide 12.5mg
Intervention code [1] 898 0
Prevention
Intervention code [2] 294946 0
Treatment: Drugs
Comparator / control treatment
Usual care (separate cardiovascular preventive medications as prescribed by the General Practitioner) for 12 months until the last participant has been randomised.
Control group
Active

Outcomes
Primary outcome [1] 1472 0
1. Adherence (self-reported current use of antiplatelet, statin and combination (2+) blood pressure lowering therapy)
Timepoint [1] 1472 0
At 1 year
Primary outcome [2] 1473 0
2. Blood pressure change
Timepoint [2] 1473 0
Over 1 year
Primary outcome [3] 1474 0
3. LDL-cholesterol change
Timepoint [3] 1474 0
Over 1 year
Secondary outcome [1] 2641 0
Dispensing of statin and 2+ blood pressure lowering agents (to be assessed via data linkage to national database)
Timepoint [1] 2641 0
At 1 year
Secondary outcome [2] 2642 0
2. Barriers to adherence
Timepoint [2] 2642 0
Over trial duration (until 12 months after the last participant has been randomised)
Secondary outcome [3] 2643 0
3. Serious adverse events
Timepoint [3] 2643 0
Over trial duration (until 12 months after the last participant has been randomised)
Secondary outcome [4] 2644 0
4. Cardiovascular events
Timepoint [4] 2644 0
Over trial duration (until 12 months after the last participant has been randomised)
Secondary outcome [5] 2645 0
Quality of life (EQ5D)
Timepoint [5] 2645 0
Over trial duration (until 12 months after the last participant has been randomised)
Secondary outcome [6] 2646 0
6. Prescriber acceptabitility
Timepoint [6] 2646 0
Over trial duration (until 12 months after the last participant has been randomised)
Secondary outcome [7] 2647 0
7. Change in other lipid fractions (HDL-cholesterol, total cholesterol, triglycerides)
Timepoint [7] 2647 0
At 1 year
Secondary outcome [8] 2648 0
8. Healthcare resource consumption and cost-effectiveness
Timepoint [8] 2648 0
Over 1 year
Secondary outcome [9] 2649 0
9. Symptoms causing withdrawal of cardivoascular medications
Timepoint [9] 2649 0
Over trial duration (until 12 months after the last participant has been randomised)
Secondary outcome [10] 264597 0
Adherence (self-reported current use of antiplatelet, statin and combination (2+) blood pressure lowering therapy)
Timepoint [10] 264597 0
Over trial duration (until 12 months after the last participant has been randomised)
Secondary outcome [11] 264598 0
Blood pressure change (if able to be assessed beyond 1 year; will be assessed by automatic sphygmomanometer)
Timepoint [11] 264598 0
Over trial duration (until 12 months after the last participant has been randomised)
Secondary outcome [12] 264599 0
Low density lipoprotein (LDL)-cholesterol change (if able to be assessed beyond 1 year; will be assessed by blood analysis)
Timepoint [12] 264599 0
Over trial duration (until 12 months after the last participant has been randomised)
Secondary outcome [13] 264600 0
Dispensing of statin and 2+ blood pressure lowering agents
Timepoint [13] 264600 0
Over trial duration (until 12 months after the last participant has been randomised)
Secondary outcome [14] 264601 0
Change in other lipid fractions (High density lipoprotein [HDL]-cholesterol, total cholesterol, triglycerides) (if able to be assessed beyond 1 year; will be assessed by blood analysis)
Timepoint [14] 264601 0
Over trial duration (until 12 months after the last participant has been randomised)

Eligibility
Key inclusion criteria
1. Adults with 5-year cardiovascular risk of at least 15%2. The General Practitioner has the opinion that all the medications in at least one of the polypills are indicated3. The General Practitioner has uncertainty whether therapy is best provided as a polypill or with usual care4. The participant is able to give informed consent.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Contraindication to any of the components of the relevant combination capsule 2. Confirmed clinical diagnosis of congestive heart failure (CHF) or currently treated CHF 3. Documented haemorrhagic stroke 4. Active stomach or duodenal ulcer 5. On warfarin 6. The General Practitioner has the opinion that changing a patient's cardiovascular medications would put the patient at risk 7. Known situation where medication regimen might be altered for a significant length of time 8. Unlikely to complete the trial or the trial procedures.

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)
The participants will be randomised by a computerized randomization program. Only the IT person who writes the codes to implement the proposed randomised allocation has permission to access the randomization program. This is an open label trial because blinding of the participants to study medication allocation will not be possible as usual care is used as the comparator. However laboratory assessment of the cholesterol primary endpoint will be blind to group allocation. After the study has finished and during the review of the results within the study team, all investigators will be blinded to treatment allocation (all results will be presented as treatment A and B). The results will remain blinded until the final statistical report has been completed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computerized randomization program which employs the minimization method will be used to generate the random allocation sequence. The stratification factors are: PHO, cardiovascular history (yes; no), level of baseline prescribing (i.e. whether or not the participant was being prescribed combination therapy – aspirin, statin, and two blood pressure lowering agents - prior to entry into the study), and ethnicity (Maori; non Maori). When a new participant comes to randomisation, we first determine his/her status for each of the stratification factors. We then count the number of participants who have the same status as the new participant in the intervention group and the control group. The new participant will be allocated in favor to the group that has smaller number of participants (p>0.5). If the numbers of participants who have the same status as the new participant are the same in the two groups, the new participant will be allocated to either the intervention or the control group at equal probability (p=0.5).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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] 284 0
New Zealand
State/province [1] 284 0
Auckland and Waikato regions

Funding & Sponsors
Funding source category [1] 1209 0
Government body
Name [1] 1209 0
Health Research Council of New Zealand (project grant)
Address [1] 1209 0
PO Box 5541, Wellesley Street, Auckland
Country [1] 1209 0
New Zealand
Funding source category [2] 1210 0
Charities/Societies/Foundations
Name [2] 1210 0
The National Heart Foundation of New Zealand (research fellowship)
Address [2] 1210 0
P O Box 17-160, Greenlane, Auckland
Country [2] 1210 0
New Zealand
Primary sponsor type
Government body
Name
Health Research Council of New Zealand
Address
PO Box 5541, Wellesley Street, Auckland
Country
New Zealand
Secondary sponsor category [1] 1070 0
None
Name [1] 1070 0
NA
Address [1] 1070 0
NA
Country [1] 1070 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295183 0
Health and Disability Ethics Committee
Ethics committee address [1] 295183 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington 6011

.
Ethics committee country [1] 295183 0
New Zealand
Date submitted for ethics approval [1] 295183 0
17/05/2006
Approval date [1] 295183 0
16/06/2006
Ethics approval number [1] 295183 0
NTX/06/06/072

Summary
Brief summary
Cardiovascular disease (CVD) is the leading cause of hospitalisation and premature death in New Zealand and the main reason for shorter life expectancy among Maori. The latest New Zealand guidelines recommend people at high risk of CVD receive long-term aspirin and medications to lower blood pressure and cholesterol, which together would cut CVD risk by around two-thirds. However most people do not receive all these medications, often because of cost, complexity and a reluctance to take (or to prescribe) multiple pills. This primary care-based trial aims to assess whether a single combination capsule (the Red Heart Pill) improves adherence to these effective medications and reduces costs compared to standard practice. Individuals will be allocated at random to receive the Red Heart Pill or to usual care. Most cardiovascular deaths occur among the group targeted in this trial, and so this new preventive approach could reduce the overall impact of CVD in New Zealand.
Trial website
Trial related presentations / publications
BMJ 2014;348:g3318 doi: 10.1136/bmj.g3318 (Published 27 May 2014)
Public notes

Contacts
Principal investigator
Name 35622 0
Prof Chris Bullen
Address 35622 0
The National Institute for Health Innovation (NIHI)
School of Population Health
The University of Auckland
Private Bag 92019 Auckland 1142 New Zealand
Country 35622 0
New Zealand
Phone 35622 0
+64 9234730
Fax 35622 0
Email 35622 0
c.bullen@auckland.ac.nz
Contact person for public queries
Name 10087 0
Ms Angela Wadham
Address 10087 0
Clinical Trials Research Unit, University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142
Country 10087 0
New Zealand
Phone 10087 0
+64 9 3737999 x 82337
Fax 10087 0
+64 9 3731710
Email 10087 0
a.wadham@auckland.ac.nz
Contact person for scientific queries
Name 1015 0
Dr Vanessa Selak
Address 1015 0
Clinical Trials Research Unit, University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142
Country 1015 0
New Zealand
Phone 1015 0
+64 9 3737999
Fax 1015 0
+64 9 3731710
Email 1015 0
impact@ctru.auckland.ac.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary