title: Update to the study protocol, including statistical analysis plan for a randomized clinical trial comparing comprehensive cardiac rehabilitation after heart valve surgery with control: the CopenHeartVR trial.
abstract: BACKGROUND
  Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising because of an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post-surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesize that a comprehensive cardiac rehabilitation program can improve physical capacity and self-assessed mental health and reduce hospitalization and healthcare costs after heart valve surgery.
  
  
  METHODS
  This randomized clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients 1:1 to an intervention or a control group, using central randomization, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise and a psycho-educational intervention comprising five consultations. The primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. The secondary outcome is self-assessed mental health measured by the standardized questionnaire Short Form-36. Long-term healthcare utilization and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design will be used to evaluate qualitative and quantitative findings, encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study.
  
  
  CONCLUSIONS
  This randomized clinical trial will contribute with evidence of whether cardiac rehabilitation should be provided after heart valve surgery. The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015).
  
  
  BACKGROUND
  Trial registered 16 March 2012; ClinicalTrials.gov ( NCT01558765 ).
authors.affiliation: The Heart Centre, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark. kirstine.laerum.sibilitz@rh.regionh.dk.|National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark. kirstine.laerum.sibilitz@rh.regionh.dk.
authors.forename: Kirstine Laerum
authors.initials: KL
authors.lastname: Sibilitz
authors.affiliation: The Heart Centre, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark. selina.kikkenborg.berg@rh.regionh.dk.|Department of Cardiology, Gentofte Hospital, Gentofte, Denmark. selina.kikkenborg.berg@rh.regionh.dk.|National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark. selina.kikkenborg.berg@rh.regionh.dk.
authors.forename: Selina Kikkenborg
authors.initials: SK
authors.lastname: Berg
authors.affiliation: Department of Cardiology, Roskilde Hospital, Roskilde, Denmark. tbh@regionsjaelland.dk.
authors.forename: Tina Birgitte
authors.initials: TB
authors.lastname: Hansen
authors.affiliation: The Heart Centre, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark. signe.stelling.risom@rh.regionh.dk.
authors.forename: Signe Stelling
authors.initials: SS
authors.lastname: Risom
authors.affiliation: The Heart Centre, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark. trine.b.rasmussen@rh.regionh.dk.|Department of Cardiology, Gentofte Hospital, Gentofte, Denmark. trine.b.rasmussen@rh.regionh.dk.
authors.forename: Trine Bernholdt
authors.initials: TB
authors.lastname: Rasmussen
authors.affiliation: The Heart Centre, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark. christian.hassager@rh.regionh.dk.
authors.forename: Christian
authors.initials: C
authors.lastname: Hassager
authors.affiliation: The Heart Centre, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark. lars.koeber@regionh.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. cgluud@ctu.dk.
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.affiliation: National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark. lct@si-folkesundhed.dk.
authors.forename: Lau Caspar
authors.initials: LC
authors.lastname: Thygesen
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. jl@ctu.dk.
authors.forename: Jane
authors.initials: J
authors.lastname: Lindschou
authors.affiliation: Cardiology Clinic, Tiefenau Hospital and University of Bern, Bern, Switzerland. jean-paul.schmid@spitalnetzbern.ch.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Schmid
authors.affiliation: National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark. r.taylor@exeter.ac.uk.|University of Exeter Medical School, Health Services Research, University of Exeter, Exeter, Devon, UK. r.taylor@exeter.ac.uk.
authors.forename: Rod S
authors.initials: RS
authors.lastname: Taylor
authors.affiliation: The Heart Centre, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark. ann.dorthe.zwisler@rh.regionh.dk.|National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark. ann.dorthe.zwisler@rh.regionh.dk.|Department of Cardiology, Holbæk Sygehus, Holbæk, Denmark. ann.dorthe.zwisler@rh.regionh.dk.
authors.forename: Ann-Dorthe
authors.initials: AD
authors.lastname: Zwisler
mesh_terms: D002985:Clinical Protocols; D003627:Data Interpretation, Statistical; D015444:Exercise; D006349:Heart Valve Diseases / Q000523:psychology / Q000534:rehabilitation* / Q000601:surgery*; D006801:Humans; D010353:Patient Education as Topic