Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial.
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.
Palmer
Scott M
SM
Duke University Medical Center and Duke Clinical Research Institute, Durham, NC, USA.
Limaye
Ajit P
AP
Banks
Missy
M
Gallup
Dianne
D
Chapman
Jeffrey
J
Lawrence
E Clinton
EC
Dunitz
Jordan
J
Milstone
Aaron
A
Reynolds
John
J
Yung
Gordon L
GL
Chan
Kevin M
KM
Aris
Robert
R
Garrity
Edward
E
Valentine
Vincent
V
McCall
Jonathan
J
Chow
Shein-Chung
SC
Davis
Robert Duane
RD
Avery
Robin
R
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
D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir