RESUMEN
BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).
Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Interferon beta-1b/uso terapéutico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Administración Oral , Adulto , Anciano , Infecciones por Coronavirus/mortalidad , Método Doble Ciego , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Hospitalización , Humanos , Inyecciones Subcutáneas , Interferon beta-1b/efectos adversos , Estimación de Kaplan-Meier , Lopinavir/efectos adversos , Masculino , Persona de Mediana Edad , Ritonavir/efectos adversos , Estadísticas no Paramétricas , Tiempo de TratamientoRESUMEN
Central venous catheters (CVCs) are life-saving and the majority of patients in intensive care units (ICUs) have them placed in order to receive medicine and fluids. However, the use of these catheters can result in serious bloodstream infections. The rate of Central Line Associated Blood Stream Infection (CLABSI) in Adult Intensive Care Units (ICUs) at King Abdulaziz Medical City Jeddah (KAMC-J) at the start of the project was 2.0/1000 line days in 2008. The Central Line (CL) Bundle by the Institute of Healthcare Improvement (IHI) was implemented at the same time with monitoring of compliance to the CL Bundle. The compliance to CL Bundle was very low at 37% in the same period. A multidisciplinary team was created to improve the compliance to the CL bundle which was expected to have an impact on the rate of CLABSI to achieve zero CLABSI events. The team continued to monitor and evaluate the progress on the compliance to the bundle as well as monitoring the CLABSI events using National Healthcare Safety Network diagnostic criteria. The real reduction in the rate of CLABSI was achieved in 2010 with 0.7/1,000 device days when the compliance to CL Bundle reached up to 98% in that year and 100% in the next two subsequent years. The project still continued and the rate continued to drop and the ultimate target of zero CLABSI was achieved in the year 2014 and maintained in the year 2015 with a sustained compliance of 100% to the CL Bundle. Successful implementation of CL Bundle can help in reducing the rates of CLABSI and achieving zero CLABSI events for a sustained period.