EVOLVE study 2007.

Methods	Study design: parallel RCT Study duration: 22 August 2006, to 31 January 2008 Study follow‐up: treatment group (21.2 months); control group (17.5 months)
Participants	Country: multinational (USA, Canada, Argentina, Brazil, Mexico, Australia, Austria, Belgium, Denmark, France, Germany, Hungary, Ireland, Italy, Netherlands, Poland, Portugal, Russia, Spain, Sweden, Switzerland, UK) Setting: multicentre (approx. 500 centres) Men or women ≥18 years of age at screening; treated with maintenance HD 3 times/wk for ≥ 3 months before randomisation; PTH ≥ 300 pg/mL; serum calcium ≥ 8.4 mg/dL; Ca x P ≥45 mg²/dL²; available during the follow‐up phase of the study; agree to be followed for study endpoints until the end of study; appropriate written informed consent must be obtained. Number: treatment group (1948); control group (1935) Mean age ± SD: 54 ± 14 years Sex (M/F): treatment group (1140/808); control group (1167/768) Exclusion criteria: unstable medical condition; parathyroidectomy; severe concomitant disease, including life‐threatening malignancy or acquired immune deficiency syndrome, or any other life‐threatening concomitant disease; received therapy with cinacalcet within 3 months of randomisation; hospitalization within 12 weeks of randomisation for any of the following events (MI, unstable angina, heart failure, peripheral vascular disease, stroke; history of seizure within 12 weeks prior to randomisation); scheduled date for kidney transplant from a known living donor; anticipated parathyroidectomy within 6 months after randomisation; currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s); receiving other investigational agent(s); known sensitivity or intolerance to any of the products to be administered; any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures; pregnant; breast feeding; child‐bearing potential and not using adequate contraceptive precautions
Interventions	Treatment group Cinacalcet: 30 to 180 mg/d Duration: 21.2 months Control group Placebo Duration: 17.5 months Co‐interventions Treatment group: vitamin D (59.3%); phosphate binders (87.8%) Control group: vitamin D (59.6%); phosphate binders (89%)
Outcomes	Composite endpoint of time to death or first nonfatal cardiovascular event (MI, hospitalisation for unstable angina, heart failure, or a peripheral vascular event) Time to individual components of primary composite endpoint Death from cardiovascular causes Stroke Bone fracture Parathyroidectomy
Notes	ITT: yes Funding: "This study was funded by Amgen, Inc and led by an executive committee composed of academic members, two sponsor members (nonvoting), and statisticians. The executive committee oversaw the design, conduct, and all analyses. Data were collected by the sponsor and shared with the executive committee throughout the study and after unblinding. The analysis was performed by the sponsor and confirmed by an independent biostatistician at Stanford University School of Medicine. The sponsor provided the active medication and matching placebo. The lead author wrote the first draft of the manuscript, and the executive committee was responsible for data interpretation and manuscript completion. The sponsor reviewed the manuscript, but decisions about the final manuscript were made by the lead author and academic members of the executive committee only."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Generated by Amgen
Allocation concealment (selection bias)	Low risk	Interactive voice‐response system
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Loss to follow‐up 7.9% of patients
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes were reported
Other bias	High risk	Sponsor on authorship; sponsor involved in writing manuscript; sponsor held data and analysed data