RESUMO
OBJECTIVE: The present study aimed to assess the long-term safety and tolerability of valsartan in hypertensive children aged 6-17 years, with or without chronic kidney disease (CKD). METHODS: This was an 18-month, open-label, multicentre, prospective study conducted in 150 patients with history of hypertension with or without CKD. The primary endpoint was long-term safety and tolerability of valsartan and valsartan-based treatments, assessed in terms of adverse events (AEs), serious AEs, laboratory measurements, estimated glomerular filtration rate (eGFR), urinalysis and electrocardiogram. RESULTS: Of 150 enrolled patients, 117 (78%) completed the study. At week 78, a clinically and statistically significant reduction in mean sitting systolic and diastolic blood pressures was observed in all patients (- 14.9 mmHg and - 10.6 mmHg, respectively). Within the first 3 months of treatment, mean urine albumin creatinine ratio decreased in CKD population, which was sustained. A higher percentage of CKD patients had at least one AE compared to non-CKD patients (85.3% vs. 73.3%, respectively). The majority of AEs were mild (50.7%) or moderate (18.7%) in severity. As expected, in patients with underlying CKD, increases in serum potassium, creatinine and blood urea nitrogen were more commonly reported compared to non-CKD patients. A > 25% decrease in Schwartz eGFR was observed in 28.4% of CKD patients and 13.5% of non-CKD patients. CONCLUSIONS: Valsartan was generally well tolerated, with an AE profile consistent with angiotensin receptor blockers in the overall population and in patients with underlying CKD. Long-term efficacy was maintained and a beneficial effect on proteinuria was observed.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Hipertensão/tratamento farmacológico , Proteinúria/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Valsartana/efeitos adversos , Adolescente , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Criança , Tosse/induzido quimicamente , Tosse/diagnóstico , Tosse/epidemiologia , Creatinina/sangue , Creatinina/urina , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Febre/induzido quimicamente , Febre/diagnóstico , Febre/epidemiologia , Taxa de Filtração Glomerular , Cefaleia/induzido quimicamente , Cefaleia/diagnóstico , Cefaleia/epidemiologia , Humanos , Hipertensão/sangue , Hipertensão/etiologia , Hipertensão/urina , Masculino , Nasofaringite/induzido quimicamente , Nasofaringite/diagnóstico , Nasofaringite/epidemiologia , Estudos Prospectivos , Proteinúria/sangue , Proteinúria/etiologia , Proteinúria/urina , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/urina , Albumina Sérica Humana/urina , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Valsartana/administração & dosagemRESUMO
AIM: This Phase IIb, randomized, double-blind, placebo-controlled trial evaluated the efficacy, safety, tolerability and pharmacokinetics of empagliflozin in patients with type 2 diabetes. METHODS: Four hundred and eight patients (treatment-naïve or after a 4-week wash-out period) were randomized to receive empagliflozin 5, 10 or 25 mg once daily, placebo or open-label metformin for 12 weeks. The primary endpoint was change in haemoglobin A1c (HbA1c) after 12 weeks. RESULTS: After 12 weeks' treatment, empagliflozin showed dose-dependent reductions in HbA1c from baseline [5 mg: -0.4%, 10 mg: -0.5%, 25 mg: -0.6%; all doses p < 0.0001 vs. placebo (+0.09%)]. Fasting plasma glucose (FPG) decreased with empagliflozin [5 mg: -1.29 mmol/l, 10 mg: -1.61 mmol/l, 25 mg: -1.72 mmol/l; all doses p < 0.0001 vs. placebo (+0.04 mmol/l)]. Body weight decreased in all empagliflozin groups (all doses p < 0.001 vs. placebo). The incidence of adverse events (AEs) was similar in the placebo (32.9%) and empagliflozin (29.1%) groups. The most frequently reported AEs on empagliflozin were pollakiuria (3.3% vs. 0% for placebo), thirst (3.3% vs. 0% for placebo) and nasopharyngitis (2.0% vs. 1.2% for placebo). AEs consistent with urinary tract infections (UTIs) were reported in four (1.6%) patients on empagliflozin vs. one (1.2%) on placebo. Genital infections were reported in five (2%) patients on empagliflozin vs. 0% on placebo. No UTIs or genital infections led to premature discontinuation. CONCLUSIONS: In patients with type 2 diabetes, empagliflozin resulted in dose-dependent, clinically meaningful reductions in HbA1c and FPG, and reductions in body weight compared with placebo. Empagliflozin was well-tolerated with a favourable safety profile.