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9/26/2014  |   4:30 PM - 6:00 PM   |  

A Randomized Trial to Prevent Congenital Cytomegalovirus–a flawed clinical trial

Objective. Passive immunization of pregnant women with a primary cytomegalovirus (CMV) infection holds promise to prevent fetal infection as reflected in two studies: one underpowered and the other non-randomized. The Maternal Fetal Network Units (MFMU) has initiated a $17million 8 year randomized trial of passive immunization to prevent fetal infection. We sought to asses the likelihood the MFMU would provide accurate results. Methods. Reviews of the MFMU protocol, of published protocols, of published papers in PubMed using avidity to time CMV maternal infections, two papers on DNA molecular clocks to time fetal infections, and multiple sample size calculations were completed. Results: Published trials indicate that without adjusting for the time of fetal infection and using seroconversion to enroll, the observed rates of HIG efficacy will not exceed 50%. Enrollment in the MFMU trial is based 90% on a low avidity rather than seroconversion. Low avidity antibodies persist for 3 to 5 months after seroconversion, hence, avidity rather then seroconversion as an enrollment criterion enhances the number of women enrolled whose fetuses are already infected when immune globulin is administered. Because the interval between seroconversion and fetal infection will remain unknown, several power analyses indicate the MFMU trial will not determine if passive immunization prevents fetal infection. This flaw is exacerbated by women being treated for up to six weeks after the low avidity is detected. Deep sequencing of CMV genomes requires several urine specimens collected from congenitally infected infants in the first years of life and allows one to retrospectively build molecular clocks to accurately estimate fetal age at the time of fetal infection in each case. Conclusion. Thus there are strong indications that this trial should not continue with its current protocol.

Stuart Adler (Primary Presenter), sadler@vcu.edu;
N/A

ASHA DISCLOSURE:

Financial - No relevant financial relationship exist.

Nonfinancial - No relevant nonfinancial relationship exist.

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