Study 3- The Kanyini Polypill Trial
Background
Cardiovascular disease (CVD) is Australia’s biggest killer and leading cause of loss of healthy life years. Aboriginal people are disproportionately affected by this burden. Current Australian therapeutic guidelines recommend, on well-established evidence, long-term treatment of individuals at high cardiovascular risk with antiplatelet, blood pressure-lowering and cholesterol-lowering drugs. However, there is a large gap between recommendations and actual practice, and innovation is required to realise the full potential of these preventive treatments.
Fixed-dose combination therapy with a “polypill” is simply a new way of providing these guideline-indicated medications and represents a major new opportunity to address this gap. It has been proposed that a polypill could improve adherence to recommended treatment by reducing the overall complexity of dosing regimens for doctors and patients, and improve access to treatment by reducing costs. The Kanyini polypill trial will rigorously test these assumptions. Improving access to effective cardiovascular medications has considerable potential to improve population health, and in particular, to help reduce variations in this gap relating to inequities in healthcare access within the Australian population.
Study Design
Open label, randomised, controlled trial (n=600) of the polypill compared to usual care for Aboriginal people at high risk of cardiovascular disease.
Aims
To assess whether provision of a polypill (containing low dose aspirin, a statin and two blood pressure lowering medicines) compared to usual cardiovascular medications improves adherence and clinical outcomes in high-risk patients at 2 years. Secondary aims are to measure prescription of combination therapy, barriers to adherence, quality of life, safety, cardiovascular events, renal events, prescriber acceptability, and healthcare resource consumption.
Patient recruitment
The study centres will be the Aboriginal Community Controlled Health Services (ACCHS) participating in the Kanyini Vascular Collaboration. Participants at high risk of CVD will be recruited through these services. Risk will be assessed using the adjusted Framingham risk assessment in accordance with the Australian National Heart Foundation and the New Zealand Guidelines Group. Based on this, inclusion criteria would be:
- any person with established CVD (Ischaemic Heart Disease, Stroke/TIA or Peripheral Vascular Disease) or
- any person with a calculated 5 year CVD risk of 15% or greater
- explore the critical components of clinical interactions between health care providers and service users that affect quality of care;
5 year CVD risk will be calculated based on the 1991 Anderson Framingham risk equation. In recognition of the potential for this equation to underestimate the actual risk in Indigenous people a 5% risk increase will be added to the calculated risk as per the NZ guidelines recommendations.
Randomisation and study medication
Eligible participants will be randomised to up to 24 months treatment with the polypill or to continued usual care:
- Polypill: version 1 - aspirin 75mg, simvastatin 40mg, lisinopril 10mg, atenolol 50mg; version 2 - aspirin 75mg, simvastatin 40mg, lisinopril 10mg, hydrochlorothiazide 12.5mg. The choice of polypill version will be at the discretion of the prescribing general practitioner. The polypill and associated charges will be supplied in accordance with local ACCHS policy for medications.
- Usual care: separate cardiovascular preventive medications (e.g. antiplatelet, blood pressure lowering and cholesterol lowering medicines) as prescribed by the ACCHS.
- For both groups, any advice and /or other interventions relating to other preventive measures, including those relating to lifestyle modification, will continue at the discretion of the responsible clinician. Similarly all changes to medication in both groups will be at the discretion of the GP.
Data collection and follow-up
Participants will be followed up for an average of 2 years. Blood pressure and fasting lipids will be measured at baseline, 12 and 24 months. Self-reported adherence will be assessed at these visits and also via follow-up with Indigenous Research Fellows (IRFs) at 1, 6, and 18 months. IRFs will also ask about barriers to adherence, quality of life, cardiovascular and other serious adverse events, and symptoms causing withdrawal of cardiovascular medications. IRFs will meet with GPs at 12 months to evaluate prescriber acceptability of the prescribing strategy (polypill or usual care) for each participant and at the end of the study to assess overall acceptability for all their patients in the trial. ACCHS records of primary care consultations, cardiovascular prescribing, and cardiovascular laboratory tests performed, plus where feasible electronic linkage to national datasets and patient reporting of cardiovascular specialist visits will contribute to an economic analysis.
Outcomes
- Primary outcomes: Self-reported current use of antiplatelet, statin, and combination (= 2) blood pressure lowering therapy), change in blood pressure, change in LDL-cholesterol, at 2 years.
- Secondary outcomes: Prescription of statin and (= 2) blood pressure lowering agents at 2 years, self-reported barriers to adherence, serious adverse events, cardiovascular events, renal events,symptoms causing withdrawal of cardiovascular medications, quality of life, prescriber acceptability, change in other lipid fractions (HDL-cholesterol, total cholesterol, triglycerides), and healthcare resource consumption.
Statistical power
Accounting for deaths and loss to follow-up, randomisation of 600 participants will provide 90% power at a two-sided 0.05 significance level to detect at least 4 mmHg difference in systolic blood pressure, and at least 0.25 mmol/L difference in total cholesterol. This assumes the standard deviation around the baseline for these variables is 14 mmHg and 0.9 mmol/L, respectively. With this number of participants there will be sufficient power to detect a 30% relative improvement in adherence (e.g. from a 50% adherence in usual care to 80% with the polypill)
Data analysis will utilise grounded theory techniques and the qualitative data management software "NVivo" will assist with the thematic analysis. A series of interim and final feedback workshops are planned in which participants will be given the opportunity to critically evaluate the study conduct and its outcomes.
Basic Study Plan
Kanyini Polypill- Study Progres
Consultations with Kanyini collaboration partner sites are progressing well and ethical approval has been granted by the relevant jurisdictions in NSW, Queensland and Central Australia. Current work involves finalizing operating procedures, database building, training and support for research staff, and consultation with pharmacies. More intensive work at each health service site will commence in April with the view to commencing recruitment in October 2009. The trial protocol is now registered with the Australian and New Zealand Clinical Trials Registry: ACTRN12608000584336.