Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial
SM Palmer, AP Limaye, M Banks, D Gallup… - Annals of internal …, 2010 - acpjournals.org
SM Palmer, AP Limaye, M Banks, D Gallup, J Chapman, EC Lawrence, J Dunitz, A Milstone…
Annals of internal medicine, 2010•acpjournals.orgBackground: 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. Design: 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 …
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. Design: 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 …
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.
Design
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)
Setting
Multicenter trial involving 11 U.S. lung transplant centers.
Patients
136 lung transplant recipients who completed 3 months of valganciclovir prophylaxis.
Intervention
9 additional months of oral valganciclovir (n = 70) or placebo (n = 66).
Measurements
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.
Limitation
Longer-term effects of extended prophylaxis were not assessed.
Conclusion
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.
Primary Funding Source
Roche Pharmaceuticals.
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