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.

Efficiency of triiodothyronine treatment on organ donor hemodynamic management and adenine nucleotide concentration.

OBJECTIVE: We compared hemodynamic values, oxygen utilization, and adenine nucleotide concentration in the extracted organs of brain-dead donors treated with triiodothyronine vs. standard support treatment. DESIGN: Prospective, randomized, double-blind controlled study. PATIENTS: We recruited 52 consecutive adult cadaveric organ donors. Inclusion criteria were diagnosis of brain-death, transplantation suitability, and family consent for donation; exclusion criterion was preexisting thyroid disease. INTERVENTIONS: The treatment group (n=29) received an intravenous bolus of 1 microg/kg triiodothyronine followed by continuous perfusion at 0.06 microg/kg per hour, and controls (n=23) received 0.9% ClNa delivered over 270 min. Hemodynamics, tonometry, thyroid hormones, and serum lactate were measured every 90 min from brain death to extraction procedure. Biopsies were processed to determine adenine nucleotides concentration. RESULTS: Hemodynamic measurements did not differ significantly in the two groups, and the inotrope dose could not be diminished after treatment. Thyrotropin levels increased from brain death to extraction procedure in controls. Thyrotropin measured 90 and 180 min after the beginning of the perfusion was significantly lower in the treatment group than controls. The Pco2 gap increased in both groups from brain death to the extraction procedure. The lactate level of the treatment group was lower than in controls. Biopsy specimens were obtained in 19 controls and in 20 donors of the treatment group; the adenine nucleotides concentration did not show any significant difference. CONCLUSIONS: Triiodothyronine did not add any benefit over the standard management of the organ donor nor did it affect the adenine nucleotides concentration of any biopsied organs.

Noninvasive pressure support versus proportional assist ventilation in acute respiratory failure.

BACKGROUND: Although conventional pressure ventilation (PSV) decreases the rate of intubation in acute respiratory failure, patient-ventilator dyssynchrony is a frequent cause of failure. In proportional assist ventilation (PAV), pressure is applied by the ventilator in proportion to the patient-generated volume and flow; therefore, there is automatic synchrony between the patient's effort and the ventilatory cycle. OBJECTIVE: The aim of this study was to compare the effects of PSV and PAV during noninvasive ventilation in the treatment of acute respiratory failure. DESIGN: Prospective randomised study. SETTING: A multidisciplinary 24-bed intensive care unit of an acute-care teaching hospital in Alicante, Spain. PATIENTS. This study included 117 consecutive adult patients with acute respiratory failure randomised to noninvasive ventilation delivered by PSV ( n = 59) or PAV ( n = 58). MEASUREMENTS AND RESULTS: There were no statistically significant differences between patients assigned to each mode of ventilation with regard to baseline parameters and aetiological diagnoses of acute respiratory failure. With regard to outcome data, no significant differences were observed between PSV and PAV in the frequency of intubation (37% vs 34%), mortality rate (29% vs 28%), and mean length of stay. Subjective comfort (0-10 visual analogue scale) was rated higher and intolerance occurred less frequently (3.4% vs 15%, P = 0.03) in the PAV than in the PSV mode. CONCLUSIONS: Although PAV seems more comfortable and intolerance occurred less frequently, no major differences exist in terms of physiological improvement or in terms of outcomes when comparing PSV and PAV.