Eficacia de la microdosis de captopril en el tratamiento de la hipertensión arterial esencial / Effectiveness of captopril microdosing in the treatment of essential arterial hypertension

Introducción: prescribir una terapéutica adecuada siempre es complejo, más aun cuando los índices de control y la seguridad de los medicamentos no satisfacen los objetivos esperados, la microdosis pudiera convertirse en una alternativa eficaz. Objetivo: evaluar la eficacia de la microdosis de captopril en el tratamiento de la hipertensión arterial esencial. Métodos: se realizó un ensayo clínico fase III, unicéntrico, aleatorizado y controlado, en el Hospital Universitario Manuel Ascunce Domenech, de Camagüey, entre enero de 2007 y diciembre de 2009. Se creó un formulario con las variables: control clinico, grupos etarios, grado hipertensivo, grado de riesgo cardiovascular, dosis mínima necesaria para control. La información obtenida fue sometida a un procesamiento estadístico de análisis en el programa SPSS versión 15.0. Se utilizaron técnicas estadísticas para hallar diferencias entre variables. Resultados: la microdosis de captopril resultó ser más eficaz que las tabletas en el tratamiento a largo plazo de la hipertensión arterial, en particular en pacientes con 60 años y más de edad, en los hipertensos grados II y III y con más alto riesgo, aún con el uso de una dosis menor. Conclusiones: la microdosis de captopril fue eficaz en el tratamiento de la hipertensión arterial esencial, al permitir mejor control clínico con una menor dosis de medicamento

Introduction: prescribing the appropriate therapeutic treatment is always a complex task, particularly when drug control and safety indices do not accomplish the expected goals. In such a context, microdosing could be an effective alternative. Objective: evaluate the effectiveness of captopril microdosing in the treatment of essential arterial hypertension. Methods: aunicenter controlled randomized phase III clinical trial was conducted at Manuel Ascunce Domenech University Hospital in the province of Camagüey from January 2007 to December 2009. A form was prepared which included the following variables: clinical control, age group, hypertension grade, cardiovascular risk grade, minimum dose required for control. The information collected was subjected to statistical processing and analysis with the software SPSS versión 15.0. Statistical techniques were used to find differences between the variables. Results: captopril microdosing was more effective than tablets for the long-term treatment of arterial hypertension, particularly in patients aged 60 and over, grade II and III hypertensives, and higher risk patients, even with the use of a smaller dose. Conclusions: captopril microdosing was found to be effective for the treatment of essential arterial hypertension, allowing a better clinical control with a smaller dose of the medication

Advances in clinical trials technologies

The reported failure rates in phase 2A and 2B for drugs completing phase 1 and proof of concept (POC) and those in phase 3 for drugs completing phase 2B are as high as 40% and 50%, respectively. These attrition rates are often due to poor design and analysis of data, such as insufficient size and duration for safety, insufficient dose range, neglected time course of drug response, poor analysis of categorical data, and neglected subgroups. Collaborations among industry, academia, and government are becoming more important in developing new clinical trial technology and bridging the gap between the discoveries in basic science and product development for public health. The benefit of using new science are emphasized in a white paper "Critical Path Initiatives" and following reports by United States Food and Drug Administration (US FDA) and consortium activities such as the Critical Path Institute of the US. When properly analyzed, biomarkers of pharmacodynamics (PD), disease progress, or toxicity can reduce failure rates in phase 2 or 3 by providing tools for an early decision of GO or NO-GO, optimal dose range, etc. Eventually this can lead to monitoring tools for outcomes of disease, better and safer therapy, and tailored medicine. In the past, traditional biomarkers were single measures of physiological or biochemical processes such as HIV burden, cancer markers, blood glucose, blood pressure, etc. Now multiple or clusters of omics measures and in vivo imaging are being added to the list. These biomarkers are best utilized when more quantitative model based drug development tools such as modeling and simulation of pharmacokinetics/PD and disease model are implemented in the overall drug development processes. New clinical trial designs such as microdosing and adaptive designs are also useful for the application of biomarkers for efficient clinical trials. Bioinformatics can also facilitate clinical trials with electronic data capturing, data transfer, and so on.