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-β=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.

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−β=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.

In recent decades, multiple efforts have been made to identify targets and therapeutic measures in the host response to infection. Haemoadsorption, under the attractive theoretical premise of inflammatory response modulation through the adsorption of soluble inflammatory mediators, could have a place as an adjuvant therapy in septic patients. The development of new devices and the recent COVID-19 pandemic has renewed interest in this therapy. The aim of this report is to describe our experience in patients with abdominal sepsis for whom haemoadsorption with a neutral microporous resin column was added to conventional treatment and to describe its performance through patient cases in the absence of large randomised trials with this device. We present five patients with abdominal sepsis admitted to a Spanish intensive care unit in which haemoadsorption was used as adjuvant treatment. The key practical aspects of the treatment protocol have been used as a guide for conducting a multicentric study. Based on the experience gathered in these five cases, the potential benefit of haemoadsorption as adjuvant therapy in patients with abdominal sepsis with multiple organ failure after control of the source of infection and adequate treatment should be investigated. Likewise, it must be defined which patients can benefit from the therapy, the most appropriate biomarkers to guide the therapy, the ideal time of initiation and discontinuation, its potential side effects, and the interaction with other therapies, especially how such treatment affects the antibiotics levels.

Background: Continuous renal replacement therapy (CRRT) is the preferred extracorporeal renal support modality for haemodynamically unstable critically ill patients with acute kidney injury (AKI). Although regional citrate anticoagulation (RCA) is primarily used to maintain circuit patency, its biological effects may extend beyond anticoagulation itself. We hypothesized that different anticoagulation strategies are associated with distinct biological modulation across complementary pathophysiological domains during CRRT. Methods: We conducted a prospective randomized pilot trial comparing RCA with systemic unfractionated heparin in critically ill adults with AKI requiring CRRT (1:1 allocation). Serial blood samples were obtained before CRRT initiation, at 1 hour and at 24 hours, with paired pre- and post-filter sampling at 1 and 24 hours. Biomarkers represented redox homeostasis (glutathione -GSH, GSSG- and their ratio), neutrophil activation (myeloperoxidase -MPO-), cellular injury (cell-free DNA -cfDNA-) and systemic inflammation (C-reactive protein -CRP-). Healthy reference participants established physiological reference values. Longitudinal analyses used linear mixed-effects models with fixed effects for time, anticoagulation strategy and their interaction. This trial was registered in the European Clinical Trials Database (EudraCT No. 2016-004361-12) and at ClinicalTrials.gov (NCT06646328). Results: Twenty patients were randomized equally to RCA or systemic heparin; baseline characteristics were comparable between groups. Among six biomarkers spanning four pathophysiological domains, only MPO showed a significant systemic time × anticoagulation interaction (P = .008); although baseline-adjusted sensitivity analyses did not confirm a significant between-group difference. GSH and cfDNA changed significantly over time irrespective of anticoagulation strategy (both P = .016), while the GSSG/GSH ratio approached a treatment-level difference (P = .067). Across the extracorporeal circuit, CRP increased significantly post-filter at both timepoints, MPO increased at 1h, and GSH showed an anticoagulation-dependent pre-to-post change at 1h. No significant differences were observed in secondary clinical outcomes. Conclusions: These pilot findings suggest that different anticoagulation strategies during CRRT may show domain-specific, rather than uniform, biological modulation, most evident within the neutrophil activation domain, with additional evidence of biomarker-specific kinetics across the extracorporeal circuit. These exploratory results are compatible with the concept that extracorporeal therapies may influence distinct domains differently, a hypothesis warranting confirmation in adequately powered, prospectively designed studies before implications for precision extracorporeal therapy can be drawn.