title: A study protocol for a randomised controlled trial evaluating clinical effects of platelet transfusion products: the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) trial.
abstract: BACKGROUND
  Patients with chemotherapy-induced thrombocytopaenia frequently experience minor and sometimes severe bleeding complications. Unrestrictive availability of safe and effective blood products is presumed by treating physicians as well as patients. Pathogen reduction technology potentially offers the opportunity to enhance safety by reducing bacterial and viral contamination of platelet products along with a potential reduction of alloimmunisation in patients receiving multiple platelet transfusions.
  
  
  METHODS
  To test efficacy, a randomised, single-blinded, multicentre controlled trial was designed to evaluate clinical non-inferiority of pathogen-reduced platelet concentrates treated by the Mirasol system, compared with standard plasma-stored platelet concentrates using the percentage of patients with WHO grade ≥ 2 bleeding complications as the primary endpoint. The upper limit of the 95% CI of the non-inferiority margin was chosen to be a ≤ 12.5% increase in this percentage. Bleeding symptoms are actively monitored on a daily basis. The adjudication of the bleeding grade is performed by 3 adjudicators, blinded to the platelet product randomisation as well as by an automated computer algorithm. Interim analyses evaluating bleeding complications as well as serious adverse events are performed after each batch of 60 patients. The study started in 2010 and patients will be enrolled up to a maximum of 618 patients, depending on the results of consecutive interim analyses. A flexible stopping rule was designed allowing stopping for non-inferiority or futility. Besides analysing effects of pathogen reduction on clinical efficacy, the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) is designed to answer several other pending questions and translational issues related to bleeding and alloimmunisation, formulated as secondary and tertiary endpoints.
  
  
  BACKGROUND
  Ethics approval was obtained in all 3 participating countries. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.
  
  
  BACKGROUND
  NTR2106; Pre-results.
authors.affiliation: Department of Hematology, HAGA Teaching Hospital Den Haag, The Netherlands Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands.
authors.forename: Paula F
authors.initials: PF
authors.lastname: Ypma
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands.
authors.forename: Pieter F
authors.initials: PF
authors.lastname: van der Meer
authors.affiliation: Faculty of Health Sciences, Department of Medicine, Canadian Blood Services, McMaster University, and Centre for Innovation, Hamilton, Ontario, Canada.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Heddle
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands.
authors.forename: Joost A
authors.initials: JA
authors.lastname: van Hilten
authors.affiliation: Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Stijnen
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rutger A
authors.initials: RA
authors.lastname: Middelburg
authors.affiliation: Department of Immunology and Transfusion Medicine, and Department of Clinical Science, Haukeland University Hospital, University of Bergen, Bergen, Norway.
authors.forename: Tor
authors.initials: T
authors.lastname: Hervig
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Johanna G
authors.initials: JG
authors.lastname: van der Bom
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands.
authors.forename: Anneke
authors.initials: A
authors.lastname: Brand
authors.affiliation: Department of Hematology, HAGA Teaching Hospital Den Haag, The Netherlands Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands.
authors.forename: Jean-Louis H
authors.initials: JL
authors.lastname: Kerkhoffs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000517:prevention & control; D017848:Blood-Borne Pathogens; D002985:Clinical Protocols; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D017713:Platelet Transfusion / Q000009:adverse effects / Q000379:methods*; D012256:Riboflavin / Q000494:pharmacology; D016037:Single-Blind Method; D013921:Thrombocytopenia / Q000628:therapy*; D016896:Treatment Outcome; D014466:Ultraviolet Rays; D014777:Virus Diseases / Q000517:prevention & control; D055815:Young Adult
chemical_list: D012256:Riboflavin
keywords: bleeding; bleeding assessment; pathogen reduction; platelet transfusion; thrombocytopenia
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