Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial
Critical care (London, England). 2022;26(1):134
BACKGROUND Recently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy. METHODS In the original RCT, patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here, we report all clinical and biological endpoints of this study. Multivariate mixed-effects modeling of NE reduction was performed to investigate characteristics that could be associated with clinical response to TPE. RESULTS A continuous effect of TPE on the reduction in NE doses over the initial 24 h was observed (SOC group: estimated NE dose reduction of 0.005 µg/kg/min per hour; TPE group: 0.018 µg/kg/min per hour, p = 0.004). Similarly, under TPE, serum lactate levels, continuously decreased over the initial 24 h in the TPE group, whereas lactate levels increased under SOC (p = 0.001). A reduction in biomarkers and disease mediators (such as PCT (p = 0.037), vWF:Ag (p < 0.001), Angpt-2 (p = 0.009), sTie-2 (p = 0.005)) along with a repletion of exhausted protective factors (such as AT-III (p = 0.026), Protein C (p = 0.012), ADAMTS-13 (p = 0.008)) could be observed in the TPE but not in the SOC group. In a multivariate mixed effects model, increasing baseline lactate levels led to greater NE dose reduction effects with TPE as opposed to SOC (p = 0.004). CONCLUSIONS Adjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. We identified that baseline lactate concentration as a potential response predictor might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints. Trial registration Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994 ).
Effects of dose of erythropoiesis stimulating agents on cardiovascular outcomes, quality of life and costs of haemodialysis. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) trial Italian
Giornale Italiano di Nefrologia. 2013;30((2):)
Background: Anaemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are the most used treatment option. In observational studies, higher haemoglobin (Hb) levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to Hb levels around 9-10 g/dL. Randomized studies found that targeting higher Hb levels with ESA causes an increased risk of death, mainly due to adverse cardiovascular outcomes. It is possible that this is mediated by ESA dose rather than haemoglobin concentration, although this hypothesis has never been formally tested. Methods: We present the protocol of the Clinical Evaluation of the Dose of Erythropoietins (C.E. DOSE) trial, which will assess the benefits and harms of a high versus a low ESA dose therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD). This is a randomized, prospective open label blinded end-point (PROBE) design trial due to enroll 900 haemodialysis patients. Patients will be randomized 1:1 to 4000 UI/week i. v. versus 18000 UI/week i. v. of epoetin alfa, beta or any other epoetin in equivalent doses. The primary outcome of the trial is a composite of cardiovascular events. In addition, quality of life and costs of these two strategies will be assessed. The study has been approved and funded by the Italian Agency of Drugs (Agenzia Italiana del Farmaco (AIFA)) within the 2006 funding plan for independent research on drugs (registered at www.clinicaltrials.gov (NCT00827021)).
Efficacy of leukocyte- and platelet-rich fibrin in wound healing: a randomized controlled clinical trial
Plastic and Reconstructive Surgery. 2012;130((6):):819e-829e.
BACKGROUND Application of platelet concentrates to wounds could speed healing. Leukocyte- and platelet-rich fibrin, a relatively recent development, stands out from the other preparations. This prospective, randomized, controlled clinical trial studied the rate of healing of postoperative hand wounds after a single application of leukocyte- and platelet-rich fibrin. METHODS Eligible patients were healthy individuals older than 18 years who had been scheduled for elective McCash (open palm) surgery for Dupuytren disease at the Plastic and Hand Surgery Department of Nice's University Hospital between August of 2007 and February of 2010. The control group received the reference care of petroleum jelly mesh (Vaselitulle), and test patients had leukocyte- and platelet-rich fibrin applied. The primary endpoint was healing delay measured in postoperative days. Secondary endpoints included pain, bleeding, and wound exudate. The trial was carried out as a single-blind trial. RESULTS Among the 68 randomized patients, 33 patients in the leukocyte- and platelet-rich fibrin group and 31 in the Vaselitulle group were analyzed. Primary endpoint analysis showed a median healing delay of 24 days (interquartile range, 18 to 28 days) for the fibrin group and 29 days (interquartile range, 26 to 35 days) for the Vaselitulle group (p = 0.014, log-rank test). Postoperative pain assessment, bleeding, and exudate were always lower for the fibrin group, but not significantly so. CONCLUSION The authors trial demonstrates that a single leukocyte- and platelet-rich fibrin application on fresh postoperative hand wounds shows a median improvement of 5 days in comparison with the standard treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, II.