title: Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial.
abstract: BACKGROUND
  Cytomegalovirus (CMV) is the most prevalent opportunistic infection after lung transplantation. Current strategies do not prevent CMV in most at-risk patients.
  
  
  OBJECTIVE
  To determine whether extending prophylaxis with oral valganciclovir from the standard 3 months to 12 months after lung transplantation is efficacious.
  
  
  METHODS
  Randomized, clinical trial. Patients were randomly assigned by a central automated system to treatment or placebo. Patients and investigators were blinded to treatment status. (ClinicalTrials.gov registration number: NCT00227370)
  
  
  METHODS
  Multicenter trial involving 11 U.S. lung transplant centers.
  
  
  METHODS
  136 lung transplant recipients who completed 3 months of valganciclovir prophylaxis.
  
  
  METHODS
  9 additional months of oral valganciclovir (n = 70) or placebo (n = 66).
  
  
  METHODS
  The primary end point was freedom from CMV disease (syndrome or tissue-invasive) on an intention-to-treat basis 300 days after randomization. Secondary end points were CMV disease severity, CMV infection, acute rejection, opportunistic infections, ganciclovir resistance, and safety.
  
  
  RESULTS
  CMV disease occurred in 32% of the short-course group versus 4% of the extended-course group (P < 0.001). Significant reductions were observed with CMV infection (64% vs. 10%; P < 0.001) and disease severity (110 000 vs. 3200 copies/mL, P = 0.009) with extended treatment. Rates of acute rejection, opportunistic infections, adverse events, CMV UL97 ganciclovir-resistance mutations, and laboratory abnormalities were similar between groups. During the 6 months after study completion, a low incidence of CMV disease was observed in both groups.
  
  
  CONCLUSIONS
  Longer-term effects of extended prophylaxis were not assessed.
  
  
  CONCLUSIONS
  In adult lung transplant recipients who have received 3 months of valganciclovir, extending prophylaxis by an additional 9 months significantly reduces CMV infection, disease, and disease severity without increased ganciclovir resistance or toxicity. A beneficial effect with regard to prevention of CMV disease seems to extend at least through 18 months after transplantation.
authors.affiliation: Duke University Medical Center and Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
authors.forename: Ajit P
authors.initials: AP
authors.lastname: Limaye
authors.forename: Missy
authors.initials: M
authors.lastname: Banks
authors.forename: Dianne
authors.initials: D
authors.lastname: Gallup
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chapman
authors.forename: E Clinton
authors.initials: EC
authors.lastname: Lawrence
authors.forename: Jordan
authors.initials: J
authors.lastname: Dunitz
authors.forename: Aaron
authors.initials: A
authors.lastname: Milstone
authors.forename: John
authors.initials: J
authors.lastname: Reynolds
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Yung
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Chan
authors.forename: Robert
authors.initials: R
authors.lastname: Aris
authors.forename: Edward
authors.initials: E
authors.lastname: Garrity
authors.forename: Vincent
authors.initials: V
authors.lastname: Valentine
authors.forename: Jonathan
authors.initials: J
authors.lastname: McCall
authors.forename: Shein-Chung
authors.initials: SC
authors.lastname: Chow
authors.forename: Robert Duane
authors.initials: RD
authors.lastname: Davis
authors.forename: Robin
authors.initials: R
authors.lastname: Avery
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000517:prevention & control*; D011024:Pneumonia, Viral / Q000517:prevention & control*; D011446:Prospective Studies; D000077562:Valganciclovir; D014766:Viremia / Q000517:prevention & control
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir