There has been no effective means of prevention or treatment for the primary cytomegalovirus (CMV) infections routinely encountered by kidney transplant patients. Because of the increased mortality and rate of renal transplant rejection associated with CMV infection, we have undertaken a controlled trial to evaluate the prophylactic value of a novel cytomegalovirus hyperimmune globulin now available as an investigational product of the Massachusetts Biologic Laboratories. The background incidence of symptomatic CMV disease among transplant recipients in whom the trial has been carried out is 75%. The CMV immune globulin (CF about 512, IHA about 8000, ELISA about 8000) has been prepared from normal donor plasma, selected on the basis of high titers of antibody to CMV by ELISA. The globulin has been formulated as an intravenous products (CMVIG-IV) so that large amounts of antibody can be easily infused. The expectation of clinical success is based upon evidence in animal studies and in humans that exogenous CMV antibody attenuates CMV disease. For clinical relevance and efficiency of study design, we have focused on kidney transplant recipients at highest risk of primary infection, i.e. those lacking CMV antibody (titer less than 8 by IHA). Patients who receive kidneys from CMV resopositive donors (IHA about 8) have been randomized to receive CMVIG-IV or no CMV specific prevention. Those patients randomized to receive CMVIG-IV receive it at the time of transplant, then every two weeks for 2 months, and then monthly for 2 more months. All patients are followed by obtaining serial blood, urine, and throat swab speciments for viral isolation over the first 12 months post transplant. Additional examinations are made upon clinical suspicion of CMV infection. In the first 24 months of the study we have enrolled 36 patients; 14 have been randomized to CMVIG-IV and 22 to no specific therapy. Preliminary analysis of 29 patients followed for a minimum of 3 months has shown a reduction in CMV syndromes from 74% in the untreated to 20% in CMVIG-IV treated. We expect to complete the necessary total patient enrollment the first year and complete the necessary follow-up and data analysis in the second year. We estimate that with a background incidence of 74%, 36 patients and 36 controls should be sufficient to test our hypothesis of an expected 50% reduction in CMV infections (Alpha = 0.05, Beta = 0.9) in the group receiving CMVIG-IV.
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