PP087. Deep trial secondary analysis: Digoxin immune fab fragment treatment has additional benefits in endogenous digitalis-like factor positive preeclamptic women.
Anahtar kelimeler
Öz
BACKGROUND
A double blinded placebo controlled clinical trial of a commercial digoxin immune Fab fragment (DIF) in preeclamptic (PE) women provided some benefit to treated subjects (1). In that study DIF, relative to placebo, prevented a decline in CrCl and lowered levels of endogenous digitalis-like factor (EDLF) activity as measured by sodium pump inhibition (SPI). However, some PE subjects had undetectable EDLF.
OBJECTIVE
The hypothesis tested was that only PE women with measureable EDLF would respond to DIF treatment and analysis of EDLF positive women might reveal treatment effects masked by inclusion of EDLF negative, and hence non-responding, PE women. Accordingly, analyses of DIF effects in EDLF positive PE women were conducted.
METHODS
Patient characteristics and study design have been published (1). In these subanalyses, subjects were considered to be EDLF positive if their plasma inhibited red cell sodium pump mediated Rb uptake. All analyses were redone for the EDLF positive subgroup by Covance Inc as in the original trial. Continuous data were analyzed by ANCOVA. Categorical data were analyzed by Barnard Exact Test.
RESULTS
45 subjects (23 DIF, 22 placebo) had baseline SPI evaluated. Of these 22% had undetectable SPI. EDLF positive PE women showed greater and more significant reductions of SPI in response to DIF at each time point (12, 24, 48 hr treatment) than in the original analysis. Subjects with undetectable EDLF showed no significant change in response to DIF or placebo. For CrCl, EDLF positive PE women showed greater and more significant preservation of CrCl compared with original analyses. Subjects absent EDLF showed deterioration of CrCl with or without DIF. Among EDLF positive PE women DIF treated women had significantly less maternal pulmonary edema (p=0.035) and significantly less intraventricular hemorrhage in their infants (p=0.015). There was the suggestion of reductions in the incidence of other maternal and neonatal abnormalities.
CONCLUSIONS
These data indicate that EDLF positive PE women are those that responded to DIF and also raise the possibility of extended benefits of DIF treatment in this group. Results support further research in this area.
