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.

Influence of Written Informed Consent for Methylphenidate on Medicine Persistence Rates in Children with Attention-Deficit Hyperactivity Disorder.

OBJECTIVE: To assess the influence of written informed consent on nonpersistence with methylphenidate treatment in children with attention-deficit hyperactivity disorder (ADHD). METHODS: We undertook a cohort study including 141 children with ADHD who started treatment with methylphenidate, with a follow-up of 6 months. The main outcome variable was nonpersistence, defined as discontinuation of treatment by the patient. Two groups were analyzed with and without written informed consent. Use of this consent was the decision of the prescribing physician because the law allows its use on a voluntary basis. The homogeneity of both groups was verified by evaluating sex, type of ADHD, methylphenidate dosage, age, severity, and other psychiatric disorders. To assess the influence of consent on nonpersistence, bootstrapping was used to determine relative risk reduction (RRR) and number needed to treat (NNT). RESULTS: Among the participants who completed follow-up, 67 provided written informed consent and 63 did not. We found the following nonpersistence frequencies in each group: (1) with written informed consent: 5 (7.5%) and (2) without written informed consent: 15 (23.8%). The clinically significant results were RRR, 0.67 ± 0.17; NNT, 7 (5-9). CONCLUSION: The use of written informed consent yielded higher persistence rates. Further studies are needed to determine whether we can use this procedure routinely in clinical practice.

Construction and internal validation of a new mortality risk score for patients admitted to the intensive care unit.

BACKGROUND: The existing models to predict mortality in intensive care units (ICU) present difficulties in clinical practice. OBJECTIVES: The aim of this study was to develop and internally validate a points system to predict mortality in the ICU, which can be applied instantly and with high discriminating power. METHODS: This cohort study comprised all patients admitted to the ICU in a Spanish region between January 2013 and April 2014, followed from admission to death or discharge (N=1113). Primary variable: ICU mortality. Secondary variables at admission: gender, Fried criteria for frailty, function scale, medical admission, cardiac arrest, cardiology admission, sepsis, mechanical ventilation, inotropic support, age, frailty index and clinical frailty scale. The sample was divided randomly into two groups (80% and 20%): construction (n=844) and internal validation (n=269). Construction: A logistic regression model was implemented and adapted to the points system. VALIDATION: the area under the ROC curve (AUC) of the model was calculated and the risk quintiles were created to determine whether differences existed between observed and expected deaths. RESULTS: The points system included: function scale, medical admission, cardiology admission, sepsis, mechanical ventilation and inotropic support. The validation showed: (i) AUC=0.95 (95% CI: 0.91-0.99, p<.001); (ii) No differences between observed and expected deaths (p=.799). CONCLUSIONS: A predictive model of mortality in the ICU has been constructed and internally validated. This model improves on the previous models through its simplicity, its discriminating power and free use. External validation studies are needed in other geographical areas.

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.