ABSTRACT
Background: Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis). Methods: This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180. Results: Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by Histoplasma (n = 51), Blastomyces (n = 18), Coccidioides (n = 13), or Sporothrix (n = 6). On day 42, clinical success was observed with SUBA-itra and c-itra on day 42 (in 69% and 67%, respectively, and on day 180 (in 60% and 65%). Patients treated with SUBA-itra exhibited less drug-level variability at days 7 (P = .03) and 14 (P = .06) of randomized treatment. The concentrations of itraconazole and hydroxyitraconazole were comparable between the 2 medications (P = .77 and P = .80, respectively). There was a trend for fewer adverse events (AEs; 74% vs 87%, respectively; P = .18) and serious AEs (10% vs 26%; P = .06) in the SUBA-itra-treated patients than in those receiving c-itra. Serious treatment-emergent AEs were less common in SUBA-itra-treated patients (12% vs 50%, respectively; P < .001). Conclusions: SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra. Clinical Trials Registration: NCT03572049.
ABSTRACT
PURPOSE: To identify factors associated with attrition in a longitudinal study of cardiovascular prevention. METHODS: Demographic, clinical, and psychosocial variables potentially associated with attrition were investigated in 1841 subjects enrolled in the southwestern Pennsylvania Heart Strategies Concentrating on Risk Evaluation study. Attrition was defined as study withdrawal, loss to follow-up, or missing 50% or more of study visits. RESULTS: Over 4 years of follow-up, 291 subjects (15.8%) met criteria for attrition. In multivariable regression models, factors that were independently associated with attrition were black race (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.55-3.16; P < .001), younger age (OR per 5-year increment, 0.88; 95% CI, 0.79-0.99; P < .05), male gender (OR, 1.79; 95% CI, 1.27-2.54; P < .05), no health insurance (OR, 2.04; 95% CI, 1.20-3.47; P < .05), obesity (OR, 1.80; 95% CI, 1.07-3.02; P < .05), CES-D depression score 16 or higher (OR, 2.02; 95% CI, 1.29-3.19; P < .05), and higher ongoing life events questionnaire score (OR, 1.09; 95% CI, 1.04-1.13; P < .001). Having a spouse/partner participating in the study was associated with lower odds of attrition (OR, 0.60; 95% CI, 0.37-0.97; P < .05). A synergistic interaction was identified between black race and depression. CONCLUSIONS: Attrition over 4 years was influenced by sociodemographic, clinical, and psychological factors that can be readily identified at study entry. Recruitment and retention strategies targeting these factors may improve participant follow-up in longitudinal cardiovascular prevention studies.
