Randomized trial of daily versus three-times-weekly prophylactic ganciclovir after lung and heart-lung transplantation.
BACKGROUND
Cytomegalovirus is an important cause of morbidity and mortality risk after lung transplantation. Ganciclovir, when given for a period of up to 3 months after lung transplantation, has been shown to reduce the incidence and severity of cytomegalovirus. However, daily prophylaxis is associated with considerable expense, inconvenience, and morbidity risk. The goal of this study was to determine whether 3-times-weekly dosage is as effective as daily prophylaxis with ganciclovir in preventing cytomegalovirus disease.


METHODS
Seventy-two consecutive subjects who had either donor or recipient cytomegalovirus seropositivity were randomized to the daily group (n = 35) or the 3-times-weekly group (n = 37). All subjects received twice-daily ganciclovir treatment for 2 weeks. Thereafter, subjects received either daily or 3-times-weekly ganciclovir dosing until 90 days after transplantation. Subjects were then monitored for 28 +/- 13 months to identify outcomes and complications.


RESULTS
There were no significant differences between the daily and 3-times-weekly groups with respect to survival free from cytomegalovirus infection or survival free from cytomegalovirus disease. In both groups, cytomegalovirus infection and disease frequently emerged after the termination of prophylaxis. However, in most cases the cytomegalovirus syndromes observed were mild and in many cases could be treated on an outpatient basis. There was no significant difference between the groups in the incidence of obliterative bronchiolitis or time to onset of grade 2 bronchiolitis obliterans syndrome. Overall patient survival was better in the daily group, but the survival advantage did not appear to be related to a reduction in cytomegalovirus-related disease. Complications of ganciclovir prophylaxis included leukopenia in 2 subjects in the 3-times-weekly group and catheter-related sepsis in 6 subjects from each group.


CONCLUSIONS
We conclude that intravenous ganciclovir given 3 times weekly for 3 months after transplantation is as effective as daily ganciclovir given for a similar time period. The 3-times-weekly dosing regimen did not result in increased infection, disease, or sequelae of cytomegalovirus infection when compared with the daily regimen.
Department of Medicine, University of Minnesota Medical School, Fairview-University Medical Center, Minneapolis, USA.
M I
MI
Hertz
C
C
Jordan
S K
SK
Savik
J M
JM
Fox
S
S
Park
R M
RM
Bolman
B M
BM
Dosland-Mullan
D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001989:Bronchiolitis Obliterans / Q000517:prevention & control; D003586:Cytomegalovirus Infections / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage* / Q000009:adverse effects; D016041:Heart-Lung Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications
D000998:Antiviral Agents; D015774:Ganciclovir