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 preve nted the development of clinical cytomegalovirus disease after heart t ransplantation. Methods: Fifty-six consecutive patients were stratifie d into two groups: cytomegalovirus-positive recipients (n = 40) and cy tomegalovirus-negative recipients of organs from cytomegalovirus-posit ive donors (n = 16). All patients received equine antithymocyte globul in induction for 7 days and maintenance doses of cyclosporine, azathio prine, and prednisolone. Ganciclovir (5 mg/kg intravenously) or matchi ng placebo was given with the premedication, three times weekly for th e first 6 weeks after transplantation and for another 2 weeks for each treated rejection episode between 6 and 12 weeks. Results: Ganciclovi r prophylaxis reduced the actuarial incidence of cytomegalovirus disea se from 71% to 11% in cytomegalovirus-mismatched patients (p < 0.01). Ganciclovir prophylaxis did not reduce the incidence of cytomegaloviru s disease in cytomegalovirus-positive recipients (25% in both placebo and ganciclovir groups) but did delay its onset and reduce its morbidi ty. There were no adverse reactions during ganciclovir administration. Gastritis was the most common clinical manifestation of cytomegalovir us disease. Pneumonitis and myocarditis were seen only in placebo-trea ted cytomegalovirus-mismatched patients. All patients with clinical cy tomegalovirus disease responded to ganciclovir, 10 mg/kg/day for 2 wee ks. Conclusions: Prolonged low-dose ganciclovir prophylaxis after hear t transplantation reduces the incidence of cytomegalovirus disease in cytomegalovirus-mismatched patients and reduces the morbidity of cytom egalovirus disease in cytomegalovirus-positive recipients.