RESUMEN
Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 µg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. Clinical Trial Registration: RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.
RESUMEN
INTRODUCCIÓN: La Diabetes Mellitus II es un problema sanitario a nivel mundial, sin excepción en nuestro país. El tratamiento farmacológico de la DM2 se basa en un esquema escalonado, que varía según las necesidades del paciente y el desarrollo de la enfermedad, así como del control glucémico del mismo. El retraso en la intensificación del tratamiento o el inicio de la insulinización, hecho que se conoce como inercia terapéutica, obedece a diferentes factores atribuibles tanto al paciente, como al sistema sanitario, aumentando el riesgo de complicaciones crónicas, tanto micro como macrovasculares. MATERIALES Y MÉTODOS: Se realizó un estudio observacional, transversal, descriptivo y de correlación. Se estudiaron 422 pacientes de consulta externa de Endocrinología y Medicina Interna del Hospital "José Carrasco Arteaga" en el año 2018, con diagnóstico de Diabetes Mellitus II que recibieron como tratamiento dos antidiabéticos orales; con el objetivo de conocer la frecuencia y factores asociados a la inercia terapéutica en estos pacientes. La recolección de datos se realizó a partir de las historias clínicas de los pacientes, en un formulario diseñado para el estudio. El análisis fue hecho en el programa SPSS v.25, aplicando estadística descriptiva y de correlación con la prueba Chi-cuadrado, con un nivel de confianza del 95%. RESULTADOS: El 59.2% de la muestra estudiada tenía 65 años o más, 54.7% fueron mujeres, 46.7% tenía sobrepeso y 36% obesidad. El 96.7% tenía tres o más años de evolución de la enfermedad, 63.7% presentaron control glucémico adecuado. La comorbilidad más frecuente fue la hipertensión arterial, que se presentó en el 61.6%. El 87% tenía Metformina más Glibenclamida como tratamiento. El 86.3% se encontraban recibiendo su actual tratamiento por más de tres meses. La inercia terapéutica se presentó en el 25.8%, y de estos casos, la inercia se relacionó con el personal de salud en el 75.2%. CONCLUSIÓN: Se presentó inercia terapéutica en el 25.8% de la muestra. La mayoría de las inercias terapéuticas están relacionadas con el personal de salud. No se encontró asociación estadísticamente significativa de la ocurrencia de la inercia terapéutica con la edad, el sexo, el nivel de instrucción, las comorbilidades, el estado nutricional o el tiempo de evolución de la DMII.(au)
BACKGROUND: Diabetes Mellitus II is a global health issue, with no exception in Ecuador. The pharmacological treatment of DM2 is based on a stepped scheme, which varies according to the patients' needs, the disease course, and the glycaemic control. The delay in the treatment intensification or the insulin initiation, known as therapeutic inertia, is caused by different factors attributable to both the patient and the health care systems, increasing the risk of both micro and macrovascular chronic complications. METHODS: we carried out an observational, cross-sectional, descriptive and correlation study. 422 patients from the Endocrinology and Internal Medicine outpatient clinic of "Hospital José Carrasco Arteaga" in 2018, with DM2 diagnosis, who received two oral antidiabetic drugs as treatment were studied; with the purpose of identifying the frequency and associated factors with therapeutic inertia in these patients. Data was collected from medical records in a form designed for this study. The data analysis was made in the SPSS v.25 software, applying descriptive statistics and correlation statistics with Chi-square test, with a confidence level of 95%. RESULTS: 59.2% of the sample was 65 years or older, 54.7% were women, 46.7% were overweight and 36% were obese. 96.7% had three or more years of diagnosis of the disease, 63.7% had adequate glycaemic control. The most frequent comorbidity was hypertension, which occurred in 61.6% patients. 87% were using Metformin plus Glibenclamide as treatment. 86.3% were receiving their current treatment for more than three months. Therapeutic inertia presented in 25.8% of the sample, and of these cases, inertia was related to health personnel in 75.2%. CONCLUSION: therapeutic inertia presented in 25.8% of the sample. Most of the therapeutic inertias were related to the health personnel. No significant statistically association was found between the occurrence of therapeutic inertia with age, sex, educational level, comorbidities, nutritional status or years of evolution of DMII.(au)