title: Detailed statistical analysis plan for the pulmonary protection trial.
abstract: BACKGROUND
  Pulmonary dysfunction complicates cardiac surgery that includes cardiopulmonary bypass. The pulmonary protection trial evaluates effect of pulmonary perfusion on pulmonary function in patients suffering from chronic obstructive pulmonary disease. This paper presents the statistical plan for the main publication to avoid risk of outcome reporting bias, selective reporting, and data-driven results as an update to the published design and method for the trial.
  
  
  RESULTS
  The pulmonary protection trial is a randomized, parallel group clinical trial that assesses the effect of pulmonary perfusion with oxygenated blood or Custodiol™ HTK (histidine-tryptophan-ketoglutarate) solution versus no pulmonary perfusion in 90 chronic obstructive pulmonary disease patients. Patients, the statistician, and the conclusion drawers are blinded to intervention allocation. The primary outcome is the oxygenation index from 10 to 15 minutes after the end of cardiopulmonary bypass until 24 hours thereafter. Secondary outcome measures are oral tracheal intubation time, days alive outside the intensive care unit, days alive outside the hospital, and 30- and 90-day mortality, and one or more of the following selected serious adverse events: pneumothorax or pleural effusion requiring drainage, major bleeding, reoperation, severe infection, cerebral event, hyperkaliemia, acute myocardial infarction, cardiac arrhythmia, renal replacement therapy, and readmission for a respiratory-related problem.
  
  
  CONCLUSIONS
  The pulmonary protection trial investigates the effect of pulmonary perfusion during cardiopulmonary bypass in chronic obstructive pulmonary disease patients. A preserved oxygenation index following pulmonary perfusion may indicate an effect and inspire to a multicenter confirmatory trial to assess a more clinically relevant outcome.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01614951, registered on 6 June 2012.
authors.affiliation: Department of Cardiothoracic Anaesthesiology, The Heart Centre, Rigshospitalet 4142, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. katrine.buggeskov@gmail.com.
authors.forename: Katrine B
authors.initials: KB
authors.lastname: Buggeskov
authors.forename: Janus C
authors.initials: JC
authors.lastname: Jakobsen
authors.forename: Niels H
authors.initials: NH
authors.lastname: Secher
authors.forename: Thomas
authors.initials: T
authors.lastname: Jonassen
authors.forename: Lars W
authors.initials: LW
authors.lastname: Andersen
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Steinbrüchel
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
mesh_terms: D006348:Cardiac Surgical Procedures / Q000009:adverse effects / Q000401:mortality / Q000706:statistics & numerical data*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000401:mortality / Q000706:statistics & numerical data*; D002985:Clinical Protocols; D003627:Data Interpretation, Statistical; D003718:Denmark; D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects; D006331:Heart Diseases / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D007430:Intraoperative Care; D007902:Length of Stay; D008168:Lung / Q000503:physiopathology*; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects; D010100:Oxygen / Q000097:blood*; D010477:Perfusion / Q000009:adverse effects / Q000379:methods / Q000401:mortality / Q000706:statistics & numerical data*; D011183:Postoperative Complications / Q000401:mortality / Q000628:therapy; D011189:Potassium Chloride / Q000008:administration & dosage / Q000009:adverse effects; D011343:Procaine / Q000008:administration & dosage / Q000009:adverse effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D012107:Research Design / Q000706:statistics & numerical data*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C039984:Bretschneider cardioplegic solution; D008353:Mannitol; D011343:Procaine; D011189:Potassium Chloride; D005947:Glucose; D010100:Oxygen