A double-blind placebo-controlled trial of low-dose ganciclovir to prevent cytomegalovirus disease after heart transplantation.

Background: The aim of this double-blind, placebo-controlled study was to determine whether a prolonged course of low-dose ganciclovir prevented the development of clinical cytomegalovirus disease after heart transplantation. Methods: Fifty-six consecutive patients were stratified into two groups: cytomegalovirus-positive recipients (n=40) and cytomegalovirus-negative recipients of organs from cytomegalovirus-positive donors (n=16). All patients received equine antithymocyte globulin induction for 7 days and maintenance doses of cyclosporine, azathioprine, and prednisolone. Ganciclovir (5 mg/kg intravenously) or matching placebo was given with the premedication, three times weekly for the first 6 weeks after transplantation and for another 2 weeks for each treated rejection episode between 6 and 12 weeks. Results: Ganciclovir prophylaxis reduced the actuarial incidence of cytomegalovirus disease from 71% to 11% in cytomegalovirus-mismatched patients (p<0.01). Ganciclovir prophylaxis did not reduce the incidence of cytomegalovirus disease in cytomegalovirus-positive recipients (25% in both placebo and ganciclovir groups) but did delay its onset and reduce its morbidity. There were no adverse reactions during ganciclovir administration. Gastritis was the most common clinical manifestation of cytomegalovirus disease. Pneumonitis and myocarditis were seen only in placebo-treated cytomegalovirus-mismatched patients. All patients with clinical cytomegalovirus disease responded to ganciclovir, 10 mg/kg/day for 2 weeks. Conclusions: Prolonged low-dose ganciclovir prophylaxis after heart transplantation reduces the incidence of cytomegalovirus disease in cytomegalovirus-mismatched patients and reduces the morbidity of cytomegalovirus disease in cytomegalovirus-positive recipients