Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: A randomized, controlled trial

Scott M. Palmer, Ajit P. Limaye, Missy Banks, Dianne Gallup, Jeffrey Chapman, E. Clinton Lawrence, Jordan Dunitz, Aaron Milstone, John Reynolds, Gordon L. Yung, Kevin M. Chan, Robert Aris, Edward Garrity, Vincent Valentine, Jonathan McCall, Shein Chung Chow, Robert Duane Davis, Robin Avery

Research output: Contribution to journalArticle

155 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)761-769
Number of pages9
JournalAnnals of Internal Medicine
Volume152
Issue number12
StatePublished - Jun 15 2010

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Lung Transplantation
Cytomegalovirus
Randomized Controlled Trials
Ganciclovir
Opportunistic Infections
Cytomegalovirus Infections
Lung
Placebos
valganciclovir
Random Allocation
Multicenter Studies
Therapeutics
Transplantation
Research Personnel
Transplants
Safety
Mutation
Incidence

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Palmer, S. M., Limaye, A. P., Banks, M., Gallup, D., Chapman, J., Lawrence, E. C., ... Avery, R. (2010). Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: A randomized, controlled trial. Annals of Internal Medicine, 152(12), 761-769.

Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation : A randomized, controlled trial. / Palmer, Scott M.; Limaye, Ajit P.; Banks, Missy; Gallup, Dianne; Chapman, Jeffrey; Lawrence, E. Clinton; Dunitz, Jordan; Milstone, Aaron; Reynolds, John; Yung, Gordon L.; Chan, Kevin M.; Aris, Robert; Garrity, Edward; Valentine, Vincent; McCall, Jonathan; Chow, Shein Chung; Davis, Robert Duane; Avery, Robin.

In: Annals of Internal Medicine, Vol. 152, No. 12, 15.06.2010, p. 761-769.

Research output: Contribution to journalArticle

Palmer, SM, Limaye, AP, Banks, M, Gallup, D, Chapman, J, Lawrence, EC, Dunitz, J, Milstone, A, Reynolds, J, Yung, GL, Chan, KM, Aris, R, Garrity, E, Valentine, V, McCall, J, Chow, SC, Davis, RD & Avery, R 2010, 'Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: A randomized, controlled trial', Annals of Internal Medicine, vol. 152, no. 12, pp. 761-769.
Palmer SM, Limaye AP, Banks M, Gallup D, Chapman J, Lawrence EC et al. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: A randomized, controlled trial. Annals of Internal Medicine. 2010 Jun 15;152(12):761-769.
Palmer, Scott M. ; Limaye, Ajit P. ; Banks, Missy ; Gallup, Dianne ; Chapman, Jeffrey ; Lawrence, E. Clinton ; Dunitz, Jordan ; Milstone, Aaron ; Reynolds, John ; Yung, Gordon L. ; Chan, Kevin M. ; Aris, Robert ; Garrity, Edward ; Valentine, Vincent ; McCall, Jonathan ; Chow, Shein Chung ; Davis, Robert Duane ; Avery, Robin. / Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation : A randomized, controlled trial. In: Annals of Internal Medicine. 2010 ; Vol. 152, No. 12. pp. 761-769.
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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. 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.",
author = "Palmer, {Scott M.} and Limaye, {Ajit P.} and Missy Banks and Dianne Gallup and Jeffrey Chapman and Lawrence, {E. Clinton} and Jordan Dunitz and Aaron Milstone and John Reynolds and Yung, {Gordon L.} and Chan, {Kevin M.} and Robert Aris and Edward Garrity and Vincent Valentine and Jonathan McCall and Chow, {Shein Chung} and Davis, {Robert Duane} and Robin Avery",
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T2 - A randomized, controlled trial

AU - Palmer, Scott M.

AU - Limaye, Ajit P.

AU - Banks, Missy

AU - Gallup, Dianne

AU - Chapman, Jeffrey

AU - Lawrence, E. Clinton

AU - Dunitz, Jordan

AU - Milstone, Aaron

AU - Reynolds, John

AU - Yung, Gordon L.

AU - Chan, Kevin M.

AU - Aris, Robert

AU - Garrity, Edward

AU - Valentine, Vincent

AU - McCall, Jonathan

AU - Chow, Shein Chung

AU - Davis, Robert Duane

AU - Avery, Robin

PY - 2010/6/15

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N2 - 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.

AB - 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.

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