IMPACT 2014.
Methods | "Open label randomised control trial" | |
Participants | 513 participants (from 91 General Practitioners); target = 600 participants in New Zealand 256 polypill; 257 comparator Mean (SD) age: 62 (8) years for both arms Maori ethnicity: 50% for both arms Women: 39% intervention; 34% comparator CAD: 35% intervention; 38% comparator DM: 44% intervention; 41% comparator Employed: 46% intervention; 44% comparator “Given the available funding resources, the recruitment target was revised down to 500, which provided 89‐93% power to detect the same differences between risk factors and 92% power to detect a 30% relative improvement in adherence.” Inclusion criteria: "Adults aged 18‐79 years at high risk of cardiovascular disease (based on either established disease (coronary, cerebrovascular, or peripheral vascular) or ≥15% five year risk of a cardiovascular event); patient’s general practitioner considered all the drugs in at least one of the two versions of the fixed‐dose combination treatment available were recommended and was uncertain if treatment was best provided as fixed‐dose combination based treatment or as usual care" Exclusion criteria: "contraindications to any of the components of the fixed dose combination, congestive heart failure, haemorrhagic stroke, active stomach or duodenal ulcer, receipt of an oral anticoagulant, concerns by the general practitioner about the risk to a patient of changing his or her cardiovascular disease drugs, impending alteration of a drug regimen for an important length of time (for example, planned coronary bypass graft operation), or the participant was unlikely to complete the trial or trial procedures" |
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Interventions | Intervention:
Comparator: "The control is usual management. Physicians in both groups are encouraged to prescribe in line with New Zealand CVD risk assessment and management guidelines.” "both trial drugs and usual drugs were dispensed through community pharmacies." "Participants were required to pay what they would normally pay to receive a single government subsidised drug" "Standard patient co‐payments of NZ$5 (£2.6; €3.1; $4.3) for each item every three months" |
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Outcomes | Primary:
Secondary:
Outcomes measured: baseline, 1, 6, 12 months, end of trial Follow‐up: median of 23 months in both arms |
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Notes | Comparator: usual care | |
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | “A central randomisation service randomly assigned (1:1) participants to fixed dose combination based treatment or usual care.” |
Allocation concealment (selection bias) | Low risk | “A central randomisation service randomly assigned (1:1) participants to fixed dose combination based treatment or usual care.” |
Blinding of participants and personnel (performance bias) All outcomes | High risk | Open label trial |
Blinding of outcome assessment (detection bias) All outcomes | Low risk | Adherence: self‐report but corroborated by pharmacy claims data but definition favours intervention (requiring second BP lowering drug, though sensitivity analyses showed similar direction of effect) LDL/SBP objectively measured and not likely too susceptible to bias SAE/CV events self‐reported but objective and reviewed by endpoints committee |
Incomplete outcome data (attrition bias) All outcomes | Low risk | Loss to follow‐up rates low and balanced |
Selective reporting (reporting bias) | Low risk | Outcome reporting largely matches protocol; 6‐month data may not have been reported but not likely different than longer term outcome trends |
Other bias | Unclear risk | Small study bias to evaluate differences in clinical outcomes |