Clinical and technical evidence

Advice

Published evidence
Strengths and limitations of the evidence
Recent and ongoing studies

Clinical and technical evidence

A literature search was carried out for this briefing in accordance with the published process and methods statement. This briefing includes the most relevant or best publicly-available evidence relating to the clinical and cost effectiveness of the technology. The literature search strategy, evidence selection methods and detailed data extraction tables are available on request by contacting mibs@nice.org.uk.

Published evidence

Five studies including a total of 92 patients are summarised in this briefing. These comprise 1 randomised controlled trial (RCT) and 4 case series. The RCT compared CytoSorb therapy with standard care in 43 patients and found no differences in mortality at 28 days or 60 days. In the case series, survival ranged from 21% to 75% and these studies found that survival was better when CytoSorb therapy was started early. No serious device-related adverse events occurred during the RCT. None of the case series reported findings relating to adverse events.

Table 1 summarises the clinical evidence as well as its strengths and limitations. There are several ongoing studies.

Strengths and limitations of the evidence

The evidence from the single RCT comparing CytoSorb therapy with standard care is currently only available in abstract form so the quality of the study could not be assessed. There are limited details of the included patients and the generalisability of the results of the studies is unclear. The RCT was small and was not powered to show differences in mortality. The RCT was funded by the manufacturer; funding for the case series was not reported.

Table 1: Summary of clinical evidence

Study size, design and location	Intervention and comparator	Outcomes	Strengths and limitations
Schadler et al. (2013a); Schadler et al. (2013b) 43 patients Randomised controlled trial Multicentre study Germany	Haemoperfusion treatment for cytokine removal (CytoSorb) and standard care. Standard care (control).	There were no serious device-related adverse events. There were no differences in 28‑day or 60‑day mortality between CytoSorb and the control. CytoSorb significantly reduced blood concentrations of cytokines.	Unable to assess the trial quality because it has only been published as an abstract in a poster. There was no between-group comparison of reduction in cytokines. Unclear duration of follow-up. Minimal details of the patients. Funded by the manufacturer. The authors noted the limitation that further research is needed to assess the device on clinical outcomes.
Kogelmann et al. (2015) 8 patients Case series Single-centre study Germany	CytoSorb as adjunctive therapy.	Overall survival was 62.5%. Slight decrease in SOFA score and SAPS II.	Small case series only reported as an abstract, so unable to assess study quality. Unclear if data collection was prospective or retrospective. No comparator group. Minimal details of the patients. Unclear duration of follow-up. Limited outcomes reported. Funding source not reported. May include patients from Kogelmann et al. (2016) study.
Kogelmann et al. (2016) 14 patients Case series Single-centre study Germany	CytoSorb as adjunctive therapy.	Overall survival was 35.7%. Survival increased if treatment started within 48 hours.	Small case series only reported as an abstract, so unable to assess study quality. Unclear if data collection was prospective or retrospective. No comparator group. Minimal details of the patients. Unclear duration of follow-up. Limited outcomes reported. Funding source not reported. May include patients from Kogelmann et al. (2015) study.
Laddomada et al. (2016) 8 patients Case series Single-centre study Italy	CytoSorb as adjunctive therapy in combination with continuous renal replacement therapy.	Six of 8 patients survived. In survivors, procalcitonin levels decreased and renal function improved.	Small case series only reported as an abstract, so unable to assess study quality. Unclear if data collection was prospective or retrospective. No comparator group. Minimal details of the patients. Unclear duration of follow-up. Limited outcomes reported. Funding source not reported.
Sathe et al. (2015) 19 patients Case series Single-centre study India	Cytosorb as an adjuvant therapy with standard care.	Four of 19 patients with predicted high mortality survived. Three of the 4 survivors had CytoSorb in less than 24 hours of admission. Almost half of those who died were given CytoSorb more than 24 hours after admission.	Small retrospective case series only reported as an abstract, so unable to assess study quality. No comparator group. Minimal details of the patients. Unclear duration of follow-up. Limited outcomes reported. Funding source not reported.
Abbreviations: SOFA, Sepsis-related Organ Failure Assessment; SAPS, Simplified Acute Physiology Score.

Recent and ongoing studies

Multi-center, efficacy study of the MedaSorb CytoSorb Hemoperfusion device as an adjunctive therapy in subjects with acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) in the setting of sepsis. ClinicalTrials.gov identifier: NCT00559130. Status: completed. Indications: acute respiratory distress syndrome, acute lung injury, sepsis. Devices: CytoSorb.
The effect of early cytokine absorption on the systemic inflammatory response syndrome and organ dysfunction in the first 48 hours of septic shock. ClinicalTrials.gov identifier: NCT02288975. Status: currently recruiting. Indications: sepsis, septic shock. Devices: CytoSorb.
Cytokine adsorption in sepsis and acute kidney injury. ClinicalTrials.gov identifier: NCT02588794. Status: currently recruiting. Indications: renal insufficiency or renal failure or end-stage renal disease with severe sepsis or septic shock. Devices: CytoSorb.
Case-observation and compassionate use: use of extracorporeal treatment with the Cytosorb-Adsorber for the reduction of postoperative hyperinflammation and SIRS after heart-surgery with the use of a heart-lung-machine. ClinicalTrials.gov identifier: NCT02265419. Status: currently recruiting. Indications: multiple organ failure. Devices: CytoSorb.
International registry on the use of the CytoSorb Adsorber in ICU patients. ClinicalTrials.gov identifier: NCT02312024. Status: currently recruiting. Indications: sepsis, need for cardiac surgery. Devices: CytoSorb.