ROADMAP.
| Study characteristics | ||
| Methods |
Study design: parallel‐group RCT Unit of randomization and analysis: individual Number randomized:
Sample size calculation: the study can "detect a 30% reduction in the risk of microalbuminuria (hazard ratio of 1.433) with 90% power at the 5% significance level ... . Thus, at least 2043 subjects are needed in each treatment arm and 328 events of microalbuminuria are expected to be observed. To compensate for withdrawals, 2200 patients are being recruited and randomized to each of the two treatment arms of the study." |
|
| Participants |
Country: 19 European countries (262 centers): Austria, Belgium, Bulgaria, the Czech Republic, Estonia, France, Germany, Hungary, Italy, Latvia, Lithuania, Poland, Romania, Russia, Slovak Republic, Spain, the Netherlands, the UK, and Ukraine (142 centers in ROADMAP‐OFU) Study period: October 2004 to July 2009 Type of diabetes: type 2 Participants' status at baseline:881 olmesartan, 877 placebo, 1758 overall
Equivalence of groups at baseline: well balanced Inclusion criteria: type 2 diabetics free of signs of urinary albumin excretion who have 1 additional cardiovascular risk factor; if hypertensive, not taking ACEi or ARBs; 18 to 75 years of age; glycated hemoglobin ≥ 6.5% or are on treatment; hypertensive (SBP ≥ 130 mmHg or DBP ≥ 80 mmHg, or both) Exclusion criteria: renal and/or renal‐vascular disease (including malignant or severe renal disease); a history of nephrectomy and/or renal transplantation, or if they require dialysis; a recent history (within 6 months of starting the study) of myocardial infarction, stroke, transient ischemic attack, myocardial revascularization or reperfusion; recent use of (within 6 months of starting the study) ARBs or ACEi or if they have severe hypertension, defined as SBP > 200 mmHg or DBP > 110 mmHg, or both; severe uncontrolled hyperlipidemia, severe heart failure, bradycardia (< 50 beats/minute at rest), a significant narrowing of the aortic bicuspid valve, a severe obstruction of cardiac outflow (hypertrophic cardiomyopathy, New York Heart Association (NYHA) stage 3 to 4) |
|
| Interventions |
Intervention 1: 40 mg olmesartan twice daily (target BP < 130/< 80 mmHg) Intervention 2: placebo tablet twice daily (target BP < 140/< 90 mmHg) In both groups, diuretics, α or β blockers, calcium channel agonists (but not ARBs or ACEi) until target blood pressure achieved. Length of follow‐up:
|
|
| Outcomes |
Primary outcome, as specified for this review: incidence of retinopathy Secondary outcomes for this review: none mentioned Other diabetic retinopathy outcomes reported: none Retinopathy diagnosis and monitoring: " ... all available data were collected from routine visits at the study center and from the primary physician" "Occurrence or progression of retinopathy as assessed by laser treatment (photocoagulation) and/or onset of vitreous haemorrhage." Intervals at which outcomes were assessed: 1.4 to 5.1 years (mean 2.3 year) and 2.1 to 6.7 years (mean 3.3 years) after last ROADMAP visit Participants (eyes) examined for outcome: 1758 Cost of interventions: not reported Quality of life: not reported Adverse outcomes: hypotension, hyperkalemia; serious events; drug‐related events, hypertension, headache; others Other outcomes: time to albuminuria, cardiovascular mortality, stroke, cardiovascular morbidity, serum creatinine, hospitalization for various bad outcomes (endstage renal disease, worsening glomerular filtration rate) |
|
| Notes |
Source of funding: Daiichi Sankyo Declaration of interest: "All steering committee members are consultants for Sankyo for the ROADMAP study." Run‐in length: 4 weeks Class(es) of antihypertensive agents assigned: ARB Degree of blood pressure control achieved:
Trial registration: NCT00185159 Other: could not find DR data in ROADMAP publications; limited to data in ROADMAP‐OFU |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Eligible patients are given a sequential number and assigned in 1:1 ratio to olmesartan medoxomil or placebo from a list produced using SAS statistical software (version 8.2; SAS Institute, Cary, North Carolina, USA) by PRA International (Reston, Virginia, USA)." |
| Allocation concealment (selection bias) | Low risk | "The original randomization list is kept at Kankyo Pharma GMBH (Munchen, Germany), but details of the treatment assigned to each patient are provided in a sealed envelope that is kept in a secure area and can be made available to investigators if required. The study medication, olmesartan medoxomil, and matching placebo are supplied as tablets in boxes that have been labelled and packaged for individual patients by Sankyo Pharma GmbH." |
| Masking (performance bias and detection bias) Primary outcomes | Low risk | Per ClinicalTrials.gov record, participants and investigators were masked to treatment assignment. |
| Incomplete outcome data (attrition bias) Primary outcome | Unclear risk | Analyzed as randomized, but withdrawals and deaths excluded from analysis. No imputation or accounting for censoring mentioned for ROADMAP. May have included/reported only participants with at least 1 follow‐up examination. Fewer than half the ROADMAP participants were reported as included in ROADMAP‐OFU, a subsequent observational follow‐up study in which the only data regarding incidence of DR were reported. |
| Selective reporting (reporting bias) | High risk | Neither incidence nor progression of retinopathy reported for main trial period, although specified as outcomes. |