ABSTRACT
Background: COVID-19 has been associated with a high prevalence of myocardial injury and increased cardiovascular morbidity. Copeptin, a marker of vasopressin release, has been previously established as a risk marker in both infectious and cardiovascular disease. Purpose: Investigate the prognostic impact of copeptin and high-sensitive cardiac troponin I (hs-cTnI) in COVID-19. Methods: This prospective, observational study of patients with laboratoryconfirmed COVID-19 infection was conducted from June 6th to November 26th, 2020 in a tertiary care hospital. Copeptin and hs-cTnI levels on admission were collected and tested for their association with the primary composite endpoint of ICU admission or 28-day mortality. Results: A total of 213 eligible patients with COVID-19 were included of whom 55 (25.8%) reached the primary endpoint. Median levels of copeptin and hs-cTnI at admission were significantly higher in patients with an adverse outcome (Copeptin 29.6 pmol/L, [IQR, 16.2-77.8] vs 17.2 pmol/L [IQR, 7.4-41.0] and hs-cTnI 22.8 ng/L [IQR, 11.5-97.5] vs 10.2 ng/L [5.5-23.1], P<0.001 respectively). ROC analysis demonstrated an optimal cutoff of 19.6 pmol/L for copeptin and 16.2 ng/L for hs-cTnI and an increase of either biomarker was significantly associated with the primary endpoint. The combination of raised hs-cTnI and copeptin yielded a superior prognostic value to individual measurement of biomarkers and was a strong prognostic marker upon multivariable logistic regression analysis (OR 4.274 [95% CI, 1.995-9.154], P<0.001). Addition of copeptin and hs-cTnI to established risk models improved C-statistics and net reclassification indices. Conclusion: The combination of raised copeptin and hs-cTnI upon admission is an independent predictor of deterioration (ICU admission) or 28-day mortality in hospitalized patients with COVID-19.
ABSTRACT
Background: Triple-negativebreast cancer (TNBC) has the highest rate of distant metastasis and poorestoverallsurvival among all breast cancer subtypes. Adagloxad simolenin (AS;OBI-822)is a therapeutic vaccine comprisingthe synthetically manufactured tumor-associatedantigen Globo H linked to the carrier protein keyhole limpethemocyanin (KLH).The KLH provides antigenic immune recognition and T-cell responses. AS isco-administered witha saponin-based adjuvant OBI-821 to induce a humoralresponse. A phase 2 trial showed that AS/OBI-821exhibiteda trend for superior progression-free survival vs placebo in patientswhose breast cancers had higher GloboHexpression. Administrationof AS/OBI-821 resulted in IgM and IgG anti-Globo H humoral response and atrendtowards improved PFS in patients with metastatic breast cancer overexpressingGlobo H. We describe therationale and design of GLORIA, an ongoing Phase III,randomized, open-label study to evaluate efficacy, safety, and quality of life(QoL) of AS plus standard of care (SOC) versus SOC alone in patients with high-risk, early-stage TNBC. The primary endpoint is invasive progression-freesurvival;secondary endpoints include overall survival, QoL, breastcancer-freeinterval, distant disease-free survival, safety, and tolerability. Trial Design: A phase 3 trial was initiated inDecember 2018 and had been slowly enrolling until being put on holddue to theCovid-19 pandemic. While the study wason hold the design waschanged from a placebo-control to astandard-of-care control trial based onfeedback from investigators and leading breast cancer advisers, that thenumberof placebo injections was a serious burden on patients. Furthermore, it wasapparent that blinding wasquestionable given the expected and frequent localskin inflammation and low-grade fevers that accompany theAS/OBI-821 vaccineadministration and the absence of these obvious clinical signs and symptoms with the normalsaline placebo control.The main changes to the protocol are as follows:Methods: Eligibility includes patients with TNBC (estrogen receptor/progesterone receptor <5%,and HER2-negative) with nonmetastatic disease and 1) either residual invasive disease of ≥1 cm in breast or ≥1 positiveaxillary node following neoadjuvantchemotherapy;Pathological Stage IIB or III disease treated with adequateadjuvant chemotherapy alone;received ≥4 cycles of standard taxane- and/oranthracycline-basedchemotherapy;randomized within 12 weeks of surgery, adjuvant multi-agent chemotherapy,or radiation therapy.Inaddition, tumors must express Globo H (H-score of ≥15 by central laboratory analysis using a validatedimmunohistochemical assay). Subjects in the AS/OBI-821 group will receive 30 μg of AS in combination with 100 μgofOBI-821.This revised study will start re-enrolling patients as soon as Covid-19 restrictions are lifted with the firstcountry being South Korea with an anticipated start date in Q4/2020.