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The study protocol has been reviewed and approved by the respective Institutional Review Board \/ Independent Ethics Committee and competent authority according to national and international regulations.Prior to patient participation in the trial, thorough study information is provided and written informed consent is obtained from each patient (or the patient\u2019s legally accepted representative) according to ICH GCP and to the regulatory and legal requirements of the participating country. The study is registered with(registration number: NCT01243424).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"We have read and understood BMC policy on declaration of interests and declare the following interests: Odd Erik Johansen is a clinical program leader employeed by Boehringer Ingelheim, Asker, Norway. Michaela Mattheus is the responsible trial statistician at Boehringer Ingelheim, Ingelheim, Germany. Prof Bernie Zinman, Toronto, Canada and Prof Mark Espeland, Winston-Salem, US, are members of the CAROLINA\u00ae executive steering committee and receive consultancy support from Boehringer Ingelheim. Prof. dr. GJ Biessels, neurologist at the University Medical Centre Utrecht receives research support from Boehringer Ingelheim.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"7"}}