The premature closure of ROMPA clinical trial: mortality reduction in septic shock by plasma adsorption.

OBJECTIVES: Coupled Plasma Filtration and Adsorption (CPFA) use in septic shock remains controversial. The objective is to clarify whether the application of high doses of CPFA in addition to the current clinical practice could reduce hospital mortality in septic shock patients in Intensive Care Units at 28 days and at 90 days follow-up. DESIGN: We designed a prospective randomised clinical trial, Reducción de la Mortalidad Plasma-Adsorción (ROMPA), to demonstrate an absolute mortality reduction of 20% (α=0.05; 1-ß=0.8; n=190 (95×2)). SETTING: Being aware of the pitfalls associated with previous medical device trials, we developed a training programme to improve CPFA use (especially clotting problems). The protocol was approved by the ethics committees of all participating centres. Circumstances beyond our control produced a change in recruitment conditions unacceptable to ROMPA researchers and the trial was discontinued. PARTICIPANTS: By closure, five centres from an initial 10 fulfilled the necessary trial criteria, with 49 patients included, 30 in the control group (CG) and 19 in the intervention group (IG). INTERVENTION: CPFA. MAIN OUTCOME MEASURES: Hospital mortality at 28 days and 90 days follow-up. RESULTS: After 28 days, 14 patients died (46.7%) from the CG and 11 (57.9%) from the IG, not reaching statistical significance (p=0.444). At 90 days, 19 patients had died (63.3%) from the CG and 11 patients (57.9%) from the IG, (p=0.878). The adjustment by propensity score or the use of the Kaplan-Meier technique failed to achieve statistical difference, neither by Intention to Treat nor by the Actual Intervention Received. CONCLUSION: We herewith present the results gained from the prematurely closed trial. The results are inconclusive due to low statistical power but we consider that this data is of interest for the scientific community and potentially necessary for any ensuing debate. REGISTER: NCT02357433 in clinicaltrials.gov.

Mortality Reduction in Septic Shock by Plasma Adsorption (ROMPA): a protocol for a randomised clinical trial.

INTRODUCTION: There is a lack of evidence in the efficacy of the coupled plasma filtration adsorption (CPFA) to reduce the mortality rate in septic shock. To fill this gap, we have designed the ROMPA study (Mortality Reduction in Septic Shock by Plasma Adsorption) to confirm whether treatment with an adequate dose of treated plasma by CPFA could confer a clinical benefit. METHODS AND ANALYSIS: Our study is a multicentric randomised clinical trial with a 28-day and 90-day follow-up and allocation ratio 1:1. Its aim is to clarify whether the application of high doses of CPFA (treated plasma ≥0.20 L/kg/day) in the first 3 days after randomisation, in addition to the current clinical practice, is able to reduce hospital mortality in patients with septic shock in intensive care units (ICUs) at 28 and 90 days after initiation of the therapy. The study will be performed in 10 ICUs in the Southeast of Spain which follow the same protocol in this disease (based on the Surviving Sepsis Campaign). Our trial is designed to be able to demonstrate an absolute mortality reduction of 20% (α=0.05; 1-ß=0.8; n=190(95×2)). The severity of the process, ensuring the recruitment of patients with a high probability of death (50% in the control group), will be achieved through an adequate stratification by using both severity scores and classical definitions of severe sepsis/septic shock and dynamic parameters. Our centres are fully aware of the many pitfalls associated with previous medical device trials. Trying to reduce these problems, we have developed a training programme to improve the CPFA use (especially clotting problems). ETHICS AND DISSEMINATION: The protocol was approved by the Ethics Committees of all the participant centres. The findings of the trial will be disseminated through peer-reviewed journals, as well as national and international conference presentations. TRIAL REGISTRATION NUMBER: NCT02357433; Pre-results.

Evolution in the management of acute myocardial infarction in the autonomous community of valencia (Spain): ten years of the primvac registry (1995-2004).

INTRODUCTION AND OBJECTIVES: Several registries of acute myocardial infarction (AMI) have been carried out in Spain, but few remain active. This work analyses the evolution of the characteristics and control of patients with AMI during the first 10 years of the PRIMVAC registry, initiated in 1995. METHODS: The demographical and clinical characteristics, therapeutic-diagnostic procedures and pharmacological treatment of patients admitted with AMI between January 1995 and December 2004, were analysed in 17 coronary centres in the Autonomous Community of Valencia (South eastern Spain). RESULTS: The mean age of the 19,719 patients recruited was of 65. The percentage of women, hypertension, hypercholestrolemia and diabetes increased during registry period. The median time of symptoms onset-hospital arrival was 151 minutes, without a decrease over the time, and the delay of thrombolysis fell from 200 to 154 minutes (p<0.01). Percentage of thrombolytic treatment oscillated between 39% and 48%. The mortality in the coronary units decreased (14.1% vs. 8.9%; p<0.001). The number of coronary angiography and percutaneous revascularisation performed increased up to 61% and 32%, respectively, of patients included. On discharge, the use of beta-blockers (29.3% vs. 66.7%), angiotensin-converting enzyme (ACE) inhibitors (41.7% vs. 57.9%) and statins (29.3% vs. 71%) went up. CONCLUSIONS: Overall mortality in the coronary unit decreased, without any variation in the incidence of serious complications. Time to thrombolysis was reduced over the time, with no significant increment in its use. The performance of coronary angiography and percutaneous revascularisation increased, with a low use of primary angioplasty. The use of beta-blockers, ACE inhibitors and statins increased at discharge.

Clinical course of acute myocardial infarction in the hypertensive patient in Eastern Spain: the PRIMVAC registry.

OBJECTIVE: The study's objective was to analyze the acute complications and prognosis of acute myocardial infarction (AMI) in hypertensive patients in Spain. METHOD: Complications and early mortality were recorded among the patients with AMI admitted to the coronary care units of the 17 hospitals in the Valencia Community (Spain) between 1995 and 2000. RESULTS: A total of 12.071 patients were registered, of whom 46% were hypertensive (5.550 cases). Atrial fibrillation was more frequent in the hypertensive group, whereas ventricular fibrillation was more common among normotensive patients. We found higher mortality rates in the hypertensive group (14.4% vs 12.4%; P<.001). However, after multivariate adjustment, hypertension was not independently associated with mortality (odds ratio: .95; P=.46), and remained independently associated with a lower risk of primary ventricular fibrillation (odds ratio: .83; P<.05). CONCLUSION: Hypertensive patients do not present comparatively greater mortality during AMI, although primary ventricular fibrillation is less common in such subjects.

[Seasonal variations in admissions for acute myocardial infarction. The PRIMVAC study]. / Variaciones estacionales en los ingresos por infarto agudo de micardio. El estudio PRIMVAC.

INTRODUCTION AND OBJECTIVES: Some authors have described seasonal variations in the incidence of acute myocardial infarction. The aim of this study was to determine the existence of seasonal rhythms in admissions for acute myocardial infarction to coronary care units, and in mortality, and to analyze the influence of age on environmental factors. PATIENTS AND METHOD: The study included a total of 8400 consecutive patients with acute myocardial infarction admitted to 12 coronary care units in the PRIMVAC registry from January 1995 to December 1999. Seasonal rhythms were analyzed with the time series method and the Cosinor regression equation. The influence of age was analyzed with the chi 2 test. RESULTS: The total number of admissions increased in winter and decreased in summer. The highest peak (acrophase) occurred in winter, with 2183 cases (r2=0.91), specifically in February, with 742 cases (r2=0.66). The age of the patients conditioned seasonal variations (P=.006), and the influence was statistically significant for patients over 65 years of age. Changes in mortality with time did not reach statistical significance. CONCLUSIONS: A seasonal rhythm in admissions for acute myocardial infarction was found, with an increase in winter and a decrease in summer. Age conditioned the effect of environmental factors on acute myocardial infarction, and patients aged 65 years or older were more sensitive to mechanisms that led to increases in admissions in winter.

Variaciones estacionales en los ingresos por infarto agudo de miocardio. El estudio PRIMVAC / Seasonal variations in admissions for acute myocardial infarction. The PRIMVAC study

Introducción y objetivos. Se ha descrito un aumento en la incidencia del infarto agudo de miocardio durante los meses fríos. Se pretende averiguar si existe un ritmo estacional en los ingresos por infarto en las unidades coronarias y en su mortalidad, y determinar si la edad condiciona el efecto de los factores ambientales. Pacientes y método. A partir del registro PRIMVAC, se estudió a 8.400 pacientes ingresados consecutivamente por infarto agudo de miocardio desde enero de 1995 a diciembre de 1999 en 12 hospitales de la Comunidad Valenciana. Se analizó el ritmo estacional mediante el estudio de series temporales y la ecuación de regresión Cosinor. El análisis de la influencia de la edad en los ingresos y la mortalidad se realizó mediante el test de la 2.Resultados. El número de ingresos por infarto agudo de miocardio aumentó en invierno y disminuyó en verano. El pico máximo (acrofase) se produjo en invierno, con 2.183 casos (r2 = 0,91), concretamente en el mes de febrero, con 742 casos (r2 = 0,66). La edad condiciona las variaciones estacionales en el número de ingresos (p = 0,006), con diferencias estadísticas a partir de los 65 años. Las variaciones en la mortalidad no alcanzan significación. Conclusiones. Existe un patrón estacional en los ingresos por infarto agudo de miocardio, con un aumento en el número de casos durante el invierno y un descenso durante el verano. La edad de los pacientes condiciona el efecto de los factores ambientales en el infarto. A partir de los 65 años, los sujetos son más sensibles a los mecanismos causantes del aumento de ingresos en invierno (AU)