RESUMO
A Gamma Variant RBD-based aluminum hydroxide adjuvanted vaccine called ARVAC CG was selected for a first in human clinical trial. Healthy male and female participants (18-55 years old) with a complete COVID-19-primary vaccine scheme were assigned to receive two intramuscular doses of either a low-dose or a high-dose of ARVAC CG. The primary endpoint was safety. The secondary objective was humoral immunogenicity. Cellular immune responses were studied as an exploratory objective. The trial was prospectively registered in PRIISA.BA (Registration Code 6564) and ANMAT and retrospectively registered in ClinicalTrials.gov (NCT05656508). Samples from participants of a surveillance strategy implemented by the Ministry of Health of the Province of Buenos Aires that were boosted with BNT162b2 were also analyzed to compare with the booster effect of ARVAC CG. ARVAC CG exhibits a satisfactory safety profile, a robust and broad booster response of neutralizing antibodies against the Ancestral strain of SARS-CoV-2 and the Gamma, Delta, Omicron BA.1 and Omicron BA.5 variants of concern and a booster effect on T cell immunity in individuals previously immunized with different COVID-19 vaccine platforms.
Assuntos
COVID-19 , Vacinas , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Adjuvantes Imunológicos , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2RESUMO
BACKGROUND: Iota-Carrageenan (I-C) is a sulfate polysaccharide synthesized by red algae, with demonstrated antiviral activity and clinical efficacy as nasal spray in the treatment of common cold. In vitro, I-C inhibits SARS-CoV-2 infection in cell culture. RESEARCH QUESTION: Can a nasal spray with Iota-Carrageenan be useful in the prophylaxis of COVID-19 in health care workers managing patients with COVID-19 disease? STUDY DESIGN AND METHODS: This is a pilot pragmatic multicenter, randomized, double-blind, placebo-controlled study assessing the use of a nasal spray containing I-C in the prophylaxis of COVID-19 in hospital personnel dedicated to care of COVID-19 patients. Clinically healthy physicians, nurses, kinesiologists and other health care providers managing patients hospitalized for COVID-19 were assigned in a 1:1 ratio to receive four daily doses of I-C spray or placebo for 21 days. The primary end point was clinical COVID-19, as confirmed by reverse transcriptase polymerase chain reaction testing, over a period of 21 days. The trial is registered at ClinicalTrials.gov (NCT04521322). RESULTS: A total of 394 individuals were randomly assigned to receive I-C or placebo. Both treatment groups had similar baseline characteristics. The incidence of COVID-19 differs significantly between subjects receiving the nasal spray with I-C (2 of 196 [1.0%]) and those receiving placebo (10 of 198 [5.0%]). Relative risk reduction: 79.8% (95% CI 5.3 to 95.4; p=0.03). Absolute risk reduction: 4% (95% CI 0.6 to 7.4). INTERPRETATION: In this pilot study a nasal spray with I-C showed significant efficacy in preventing COVID-19 in health care workers managing patients with COVID-19 disease. CLINICAL TRIALS REGISTRATION: NCT04521322.
RESUMO
The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette-Guerin (BCG) and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) is being tested against medium-dose IFN-α2b in stages IIB-III cutaneous melanoma (CM) patients (pts) after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (ClinicalTrials.gov: NCT01729663). Thirty-one pts were randomized to the CSF-470 vaccine (n = 20) or to the IFN-α2b arm (n = 11). During the 2-year treatment, immunized pts should receive 13 vaccinations. On day 1 of each visit, 1.6 × 107 irradiated CSF-470 cells plus 106 colony-forming units BCG plus 100 µg rhGM-CSF were administered intradermally, followed on days 2-4 by 100 µg rhGM-CSF. IFN-α2b pts should receive 10 million units (MU)/day/5 days a week for 4 weeks; then 5 MU thrice weekly for 23 months. Toxicity and quality of life (QOL) were evaluated at each visit. With a mean and a maximum follow-up of 39.4 and 83 months, respectively, a significant benefit in the distant metastasis-free survival (DMFS) for CSF-470 was observed (p = 0.022). Immune monitoring showed an increase in antitumoral cellular and humoral response in vaccinated pts. CSF-470 was well tolerated; 20/20 pts presented grades 1-2 dermic reactions at the vaccination site; 3/20 pts presented grade 3 allergic reactions. Other adverse events (AEs) were grade 1. Pts in the IFN-α2b arm presented grades 2-3 hematological (7/11), hepatic (2/11), and cardiac (1/11) toxicity; AEs in 9/11 pts forced treatment interruptions. QOL was significantly superior in the vaccine arm (p < 0.0001). Our results suggest that CSF-470 vaccine plus BCG plus GM-CSF can significantly prolong, with lower toxicity, the DMFS of high-risk CM pts with respect to medium-dose IFN-α2b. The continuation of a Phase III part of the CASVAC-0401 study is encouraged.
RESUMO
Objetivo: El objetivo del trabajo APREDIA (Anemia prediálisis) fue detectar la prevalencia de la anemia en pacientes con Enfermedad Renal Crónica (ERC) etapa prediálisis y evaluar su manejo. Material y métodos: Para ello se realizó un relevamiento de datos de corte transversal, de pacientes con un filtrado glomerular (FG) ≤ 44,4 ml/min (Cockcroft Gault), en los que se excluyeron otras causas de anemia y/o evidencia de sangrado activo. La anemia se definió por hemoglobina (Hb) < 13 g/dl en hombres y 12 g/dl en mujeres. Se solicitaron datos acerca de: causa de ERC, laboratorios y tratamientos. Resultados: Se incluyeron datos de 611 pacientes (edad 71,4 ± 14 años). El 50% tenía 2 o más años de diagnóstico de ERC. El 71,7% presentaba un valor de Hb compatible con anemia (74% varones; 69% mujeres); el 64% y el 91% entre pacientes con FG entre 44,4 y 30 ml/min y ≤ 15 ml/min, respectivamente. El valor medio de Hb de toda la población fue de 11,4 g/dl, siendo más bajo a medida que disminuía el FG. Sólo el 35 % de los pacientes tenía un control de ferritina y ferremia, y sólo el 50,9% de los que tenían anemia recibía ferroterapia, la mayoría por vía oral. El 22,2% de los pacientes anémicos recibían agentes estimulantes de la eritropoyesis (AEE), el 31,2% y el 10,4% de los que tenían un FG < 30 ml/min y entre 30 y 44,4 ml/min, respectivamente. No hubo diferencias en los valores de Hb entre los que recibían AEE en los distintos estadíos, pero sí la hubo entre quienes no recibían AEE. Conclusiones: La anemia en el período predialítico de la ERC esta subdiagnosticada y subtratada, lo que explica el frecuente ingreso de los pacientes a terapia sustitutiva con signos de anemia severa, insuficientemente tratada.
The objective of APREDIA (Anemia predialysis) study was to detect the prevalence of anemia in patients with Chronic Kidney Disease (CKD) in predialysis stage and evaluate its management. For this purpose, a cross-sectional data survey of patients with a glomerular filtration rate (GF) ≤ 44.4 ml/min (Cockcroft Gault) was performed, in which other causes of anemia and/or evidence of active bleeding were excluded. Hemoglobin (Hb) < 13 g/dl for men and 12 g/dl for women defined anemia in our study. Data requested were: cause of CKD, laboratories, and treatments. Data of 611 patients (age 71.4 ± 14 years) were included. 50% of patients had been diagnosed with CKD 2 or more years ago. 71.7% had a Hb value compatible with anemia (74% males; 69% females); 64% of those who had GF between 44.4 and 30 ml/ min and 91% of those with GF ≤ 15 ml/min. The Hb medium value of the whole population was 11.4 g/dl, being lower as the GF decreased. Only 35% of the patients had a ferritin and iron serum measures, and only 50.9% of those who had anemia were receiving iron therapy, most of them orally. 22.2% of anemic patients received erythropoiesis-stimulating agents (ESAs), 31.2% of those who had a GF < 30 ml/min and 10.4% of those who had GF between 30 and 44.4 ml/ min. There were no differences in the levels of Hb among those who received ESAs in the different stages, but there was a difference among those who did not receive ESAs.According to our observation, we conclude that anemia in the predialysis stage of the CKD is underdiagnosed and undertreated. This explains why in patients who begin renal replacement therapy, signs of severe anemia are so common.
Assuntos
Humanos , Masculino , Feminino , Anemia , Insuficiência Renal CrônicaRESUMO
La hiperfosfatemia de la enfermedad renal crónica (ERC) se asocia a severas complicaciones y aumento de la morbimortalidad. El 95% de los pacientes en diálisis debe usar quelantes de fósforo para su control. La mala tolerancia y complicaciones de estos tratamientos dificultan su cumplimiento y eficacia. Este estudio compara el uso de carbonato y/o acetato de calcio en comprimidos con una emulsión de carbonato de calcio (CO3Ca) para el manejo de esta hiperfosfatemia.
Assuntos
Carbonato de Cálcio , Hiperfosfatemia , Distúrbio Mineral e Ósseo na Doença Renal CrônicaRESUMO
A randomised trial was conducted in 285 adults not immune to hepatitis B (HB) to compare the safety and immunogenicity of a commercial aluminium-adjuvanted HB vaccine with and without an additional new adjuvant (AgB/RC-210-04 or AgB study groups, respectively). The additional adjuvant RC-529 is a fully synthetic monosaccharide mimetic of monophosphoryl lipid A. Subjects in the AgB/RC-210-04 (n=136) and AgB (n=149) groups were vaccinated intramuscularly on days 0, 30, and 180, according to the standard vaccination schedule for hepatitis B vaccines. Serum levels of anti-HBs were measured on days 30, 60, 90, 180, and 210. Standard safety assessments were made throughout the study period. The rates of seroprotection (anti-HBs > or =10.0 mIU/ml) were significantly greater for the AgB/RC-210-04 group at all time points: at day 90, the seroprotection rate, the primary endpoint of the trial, was 99% for AgB/RC-210-04 compared with 84% for AgB (p<0.0001). Similarly, geometric mean anti-HBs titres were significantly higher at all time points for the AgB/RC-210-04 group. There were more local reactions in the AgB/RC-210-04 group, however they were transient and this double-adjuvanted formulation was well tolerated. We conclude that the addition of a synthetic adjuvant to the AgB vaccine significantly enhanced the immunogenicity of the commercial vaccine AgB. The results indicate furthermore that a two-dose regime of the double-adjuvanted vaccine (schedule: 0-1 month) may be sufficient to achieve seroprotection in nearly 100% of individuals.
Assuntos
Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/imunologia , Hepatite B/imunologia , Hepatite B/prevenção & controle , 1,2-Dipalmitoilfosfatidilcolina , Adjuvantes Imunológicos , Adolescente , Adulto , Estudos de Coortes , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Excipientes , Feminino , Anticorpos Anti-Hepatite B/análise , Anticorpos Anti-Hepatite B/biossíntese , Antígenos de Superfície da Hepatite B/análise , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Humanos , Masculino , SuspensõesRESUMO
El objetivo fue determinar el estado nutricional (EN) de una población en hemodiálisis crónica (HDC) y correlacionarlo con la dosis de diálisis y la morbimortalidad. Se evaluaron 55 pacientes (27 hombres y 28 mujeres, con una edad de 47 + 15 años y tiempo previo en HDC de 54,6 + 47,6). El EN se clasificó como: adecuado, desnutrición leve, desnutrición moderada y desnutrición severa, utilizando un puntaje confeccionado tomando en cuenta datos habituales de laboratorio (capacidad total de fijación del hierro [TIBC], albúmina y colesterol), impresión clínica y mediciones antropométricas (índice de masa corporal [BMI], circunferencia media braquial, plieque cutáneo tricipital [PCT], circunferencia muscular media braquial [CMMB]). Se realizó, además, autorregistro de la ingesta por 7 días y se determinó la tasa de catabolismo proteico (PCR). La ingesta calórica fue de 27 + 13 kcal/kg/día y la proteica, 1,2 + 0,5 g/kg/día. No hubo correlación entre esta última y la PCR. El 49,1 por ciento de los pacientes presentó desnutrición moderada a severa; sólo 9 pacientes (16, 4 por ciento) presentaron un EN adecuado. Sin embargo, las mediciones antropométricas evidenciaron que el PT, el CMMB, y el BMI fueron normales en el 54,5 por ciento, 45 por ciento y 72,7 por ciento de los pacientes, respectivamente. No se encontró correlación entre el EN y la edad de inicio de HDC, el sexo, la creatininemia, la dosis de diálisis (Kt/V x = 1,24 + 0,12), la PCR y la morbilidad. Mayor tiempo en diálisis se asoció con peor estado nutricional (p < 0,01). Asimismo, el EN correlacionó significativamente con la albúmina (p < 0,01) y con la mortalidad (p < 0,05); el riesgo estimado de muerte fue 9,45 veces mayor en los pacientes con desnutrición moderada y severa. (AU)
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estado Nutricional , Diálise Renal , Insuficiência Renal/terapia , Ingestão de Energia , Diálise Renal/mortalidade , Desnutrição Proteico-Calórica/mortalidade , Insuficiência Renal/epidemiologia , Estudos Prospectivos , Seguimentos , MorbidadeRESUMO
El objetivo fue determinar el estado nutricional (EN) de una población en hemodiálisis crónica (HDC) y correlacionarlo con la dosis de diálisis y la morbimortalidad. Se evaluaron 55 pacientes (27 hombres y 28 mujeres, con una edad de 47 + 15 años y tiempo previo en HDC de 54,6 + 47,6). El EN se clasificó como: adecuado, desnutrición leve, desnutrición moderada y desnutrición severa, utilizando un puntaje confeccionado tomando en cuenta datos habituales de laboratorio (capacidad total de fijación del hierro [TIBC], albúmina y colesterol), impresión clínica y mediciones antropométricas (índice de masa corporal [BMI], circunferencia media braquial, plieque cutáneo tricipital [PCT], circunferencia muscular media braquial [CMMB]). Se realizó, además, autorregistro de la ingesta por 7 días y se determinó la tasa de catabolismo proteico (PCR). La ingesta calórica fue de 27 + 13 kcal/kg/día y la proteica, 1,2 + 0,5 g/kg/día. No hubo correlación entre esta última y la PCR. El 49,1 por ciento de los pacientes presentó desnutrición moderada a severa; sólo 9 pacientes (16, 4 por ciento) presentaron un EN adecuado. Sin embargo, las mediciones antropométricas evidenciaron que el PT, el CMMB, y el BMI fueron normales en el 54,5 por ciento, 45 por ciento y 72,7 por ciento de los pacientes, respectivamente. No se encontró correlación entre el EN y la edad de inicio de HDC, el sexo, la creatininemia, la dosis de diálisis (Kt/V x = 1,24 + 0,12), la PCR y la morbilidad. Mayor tiempo en diálisis se asoció con peor estado nutricional (p < 0,01). Asimismo, el EN correlacionó significativamente con la albúmina (p < 0,01) y con la mortalidad (p < 0,05); el riesgo estimado de muerte fue 9,45 veces mayor en los pacientes con desnutrición moderada y severa.