Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

The global challenges of the long COVID-19 in adults and children

Institución Universitaria Visión de las Américas. Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Risaralda, Colombia / Universidad Científica del Sur. Faculty of Health Sciences. Lima, Peru / Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Universidad Científica del Sur. Faculty of Health Sciences. Lima, Peru.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Municipal Autonomous Government of Cochabamba. Municipal Secretary of Health. Direction of First Level. Cochabamba, Bolivia.Franz Tamayo University. National Research Coordination. La Paz, Bolivia.Universidad Continental. Research Unit. Huancayo, Peru.Universidad Nacional de Colombia. Department of Pediatrics. Bogotá, DC, Colombia / Fundación HOMI. Hospital Pediátrico La Misericordia. Division of Infectious Diseases. Bogotá, DC, Colombia / Fundación Hospital Infantil Universitario de San José. Bogotá, DC, Colombia.Hemera Unidad de Infectología IPS SAS. Bogota, Colombia.Hospital San Vicente Fundación. Rionegro, Antioquia, Colombia.Clinica Imbanaco Grupo Quironsalud. Cali, Colombia / Universidad Santiago de Cali. Cali, Colombia / Clinica de Occidente. Cali, Colombia / Clinica Sebastián de Belalcazar. Valle del Cauca, Colombia.University of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina.Universidade Estadual Paulista Júlio de Mesquita Filho. Botucatu Medical School. Infectious Diseases Department. São Paulo, SP, Brazil / Brazilian Society for Infectious Diseases. São Paulo, SP, Brazil.Institute of Infectious Diseases Emilio Ribas. São Paulo, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Pará. Faculdade de Medicina. Belém, PA, Brazil.University of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina / Hospital de Enfermedades Infecciosas F. J. Muñiz. Buenos Aires, Argentina.University of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina / Hospital de Enfermedades Infecciosas F. J. Muñiz. Buenos Aires, Argentina.Centro de Referencia de Salud Dr. Salvador Allende Gossens. Policlínico Neurología. Unidad Procedimientos. Santiago de Chile, Chile.Hospital Salvador Bienvenido Gautier. Santo Domingo, Dominican Republic.Universidad Central del Ecuador. Jefatura de Cátedra de Enfermedades Infecciosas. Quito, Ecuador.Universidad Autónoma de Santo Domingo. Santo Domingo, Dominican Republic.Hospital Roosevelt. Guatemala City, GuatemalaNational Autonomous University of Honduras. Institute for Research in Medical Sciences and Right to Health. Tegucigalpa, Honduras.National Clinical Coordinator COVID-19-WHO Studies. Colombia / Universidad Nacional de Colombia. Facultad de Medicina. Clinica Colsanitas. Clinica Universitaria Colombia. Colombia.Think Vaccines LLC. Houston, Texas, USA.Universidad Simón Bolívar. Centro de Investigación en Ciencias de la Vida. Barranquilla, Colombia / Grupo de Expertos Clínicos Secretaria de Salud de Barranquilla. Barranquilla, Colombia.Universidad San Ignacio de Loyola. Vicerrectorado de Investigación. Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud. Lima, Peru.Hospital Evangélico de Montevideo. Montevideo, Uruguay.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia / University of California. School of Public Health. Division of Infectious Diseases and Vaccinology. Berkeley, CA, USA.Universidad Central de Venezuela. Faculty of Medicine. Caracas, Venezuela.Universidad Central de Venezuela. Faculty of Medicine. Caracas, Venezuela / Biomedical Research and Therapeutic Vaccines Institute. Ciudad Bolivar, Venezuela.University of Colorado Anschutz Medical Campus. School of Medicine. Division of Infectious Diseases. Aurora, CO, USA.Tribhuvan University Teaching Hospital. Institute of Medicine. Kathmandu, Nepal / Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth. Dr. D. Y. Patil Medical College. Department of Microbiology. Pune, Maharashtra, India / Dr. D.Y. Patil Dental College and Hospital. Department of Public Health Dentistry. Dr. D.Y. Patil Vidyapeeth, Maharashtra, India.Universidad Cesar Vallejo. Escuela de Medicina. Trujillo, Peru.Universidad de San Martín de Porres. Facultad de Medicina Humana. Chiclayo, Peru.Friedrich Schiller University Jena. Institute of Microbiology. Beutenbergstraße, Jena, Germany / Pontificia Universidad Católica del Ecuador. School of Medicine. Postgraduate Program in Infectious Diseases. Quito, Ecuador.Universidad Simón Bolivar. Faculty of Health Sciences. Barranquilla, Colombia.Johns Hopkins Aramco Healthcare. Specialty Internal Medicine and Quality Department. Dhahran, Saudi Arabia / Indiana University School of Medicine. Department of Medicine. Infectious Disease Division. Indianapolis, IN, USA / Johns Hopkins University School of Medicine. Department of Medicine. Infectious Disease Division. Baltimore, MD, USA.Johns Hopkins Aramco Healthcare. Molecular Diagnostic Laboratory. Dhahran, Saudi Arabia / Alfaisal University. College of Medicine. Riyadh, Saudi Arabia / The University of Haripur. Department of Public Health and Nutrition. Haripur, Pakistan.VM Medicalpark Samsun Hospital. Department of Infectious Diseases. Samsun, Turkey.University of Miami. Miller School of Medicine. Department of Medicine. Division of Infectious Diseases. Miami, FL, USA.Caja Costarricense de Seguro Social. Centro de Ciencias Médicas. Hospital Nacional de Niños Dr. Carlos Sáenz Herrera. Servicio de Infectología Pediátrica. San José, Costa Rica / Instituto de Investigación en Ciencias Médicas. San José, Costa Rica / Universidad de Ciencias Médicas. Facultad de Medicina. Cátedra de Pediatría. San José, Costa Rica

Alirocumab and cardiovascular outcomes after acute coronary syndrome

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Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

BACKGROUN