Advice
Clinical and technical evidence
Clinical and technical evidence
A literature search was carried out for this briefing in accordance with NICE's interim process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting mibs@nice.org.uk.
Published evidence
There are 6 studies summarised in this briefing, including a total of 209 people.
The evidence includes 4 observational studies, of which 3 had a comparator group, 1 bootstrap analysis based on a retrospective case series and 1 case study. The studies investigated the effect of CytoSorb on ticagrelor removal and subsequent risk of bleeding.
There is an in vitro study that is not presented below (Angheloiu et al. 2017). This study showed that CytoSorb can remove ticagrelor from bovine serum albumin solution and human blood samples.
Overall assessment of the evidence
The evidence for the technology is of low methodological quality, and all the studies are small in terms of patient numbers. All studies were done in Germany, apart from 1 that was done in Croatia. Three studies had a comparator, looking at emergency cardiac surgery without adsorption. The studies suggest that using CytoSorb to remove ticagrelor during surgery is a safe and effective method to reduce bleeding complications. Further evidence is needed comparing CytoSorb with standard care for people having urgent or emergency cardiac surgery, with a large sample size.
Hassan et al. (2019)
Key outcomes
All people in the study had therapy with either ticagrelor (n=43) or rivaroxaban (n=12). Standardised CytoSorb adsorption was installed into the heart-lung machine for 39 patients. In the Cytosorb ticagrelor adsorption group, no re‑thoracotomies had to be done, compared with 4 in the control group. Mean drainage volume over 24 hours was 350 ml in the CytoSorb ticagrelor adsorption group compared with 890 ml in the ticagrelor control group (p=0.0037). Compared with the CytoSorb adsorption group, multiple bleeding complications occurred in the control group that were associated with more transfusions of red blood cells (p=0.0119) and platelets (p=0.0475). CytoSorb adsorption significantly influenced the length of hospital stay in the intensive care unit (ICU; p=0.0141) and total length of hospital stay (p=0.0244).
Strengths and limitations
This study suggests that using CytoSorb to remove ticagrelor and rivaroxaban during surgery is a safe and effective method to reduce bleeding complications. The authors noted that it was unclear how much adsorption time is needed to fully clear ticagrelor from the body. This was the first study to report on the use of CytoSorb and the authors recommended further randomised prospective studies to confirm their findings.
Hassan et al. (2020a)
Key outcomes
All procedures were done as isolated CABG surgery with the use of both thoracic arteries in 65.5% of people for complete arterial revascularisations (n=36). Ticagrelor adsorption was done during cardiopulmonary bypass over 103 minutes (plus or minus 35 minutes). Mean drainage volume over 24 hours was 480 ml (plus or minus 211 ml). Only 1 re‑thoracotomy (1.8%) for surgical bleeding was done. Mean length of stay in the ICU was 2 days (plus or minus 3 days) and total length of hospital stay was 12 days (plus or minus 5 days). Most people in the study did not need transfusion of blood products. Red blood cell transfusion was done in 20% (n=11) and platelet transfusion in 30.9% (n=17). The 30‑day mortality rate was 1.8%.
Strengths and limitations
This study suggests that using CytoSorb adsorption for people taking ticagrelor having emergency CABG for acute coronary syndrome is a safe and effective method, providing low rates of bleeding complications. It is unclear whether the sample from this study is independent from the sample in the Hassan et al. 2019 study. This study is reported in conference abstract form only, so is limited in detail.
Hassan et al. (2020b)
Key outcomes
Compared with the control group, CytoSorb patients had 72% fewer transfusions of red blood cells or platelets, 33% fewer days in ICU, and 18% shorter operation times. A significantly higher re‑thoracotomy rate in the control group was also associated with prolonged ICU stay and use of more blood products. Cost of ICU stay had the highest impact on the level of cost savings. CytoSorb was less costly regardless of differences in cost‑driving variables. The economic benefit was calculated as €3.656 per person without reimbursement.
Hassan et al. (2020c)
Study size, design and location
Observational study in 21 people with acute type A aortic dissection having emergency cardiac surgery in Germany.
Key outcomes
All people in the study were taking either ticagrelor (n=12) or rivaroxaban (n=9). In 10 out of 21 cases, the standardised adsorber was installed into the heart-lung machine (AD group) and compared with 11 patients without adsorption (WAD group). In the AD group drainage volumes over 24 hours were 500 ml (interquartile range [IQR] 450 to 675) after ticagrelor administration, and 450 ml (IQR 310 to 430) after rivaroxaban therapy. There were multiple bleeding complications in the WAD group. These were associated with longer total operation time, higher drainage volumes (p<0.05), and more transfusions (p<0.05). In the AD group no re‑thoracotomies had to be done compared with a significantly higher re‑thoracotomy rate in the WAD group.
Strengths and limitations
This study suggests that CytoSorb is safe and effective in preventing major bleeding complications in people with acute type A aortic dissection needing emergency cardiac surgery. This study is reported in conference presentation form only, so is limited in detail. The abstract is not available to access online.
Mair et al. (2020)
Study size, design and location
Case study of 1 person having urgent off-pump coronary artery bypass surgery in Germany.
Key outcomes
CytoSorb adsorption was started 1 hour before the operation and was continued for 1.5 hours during the operation. The patient was extubated on the same day of the surgery. By the first day after the operation, low‑dose norepinephrine was stopped. The chest tubes delivered 570 ml in 24 hours and were removed on the second day after the operation. Haemoglobin dropped from 14.0 g/dl before the operation to 8.5 g/dl after the operation. This was treated with 1 unit of red blood cells. After the operation, maximum creatine kinase levels were 380 U/l (normal range, 40 U/l to 310 U/l), and the creatine kinase myocardial band remained in normal range. The patient made a good recovery, and at discharge received a renewed prescription for dual antiplatelet therapy and rivaroxaban. At 6‑month follow up the patient had good pump function, sinus rhythm, and no cardiac symptoms.
Strengths and limitations
This single case suggests that using CytoSorb haemoadsorption appears to be safe and effective to reduce bleeding in people taking ticagrelor or rivaroxaban. This case study has several limitations, including the use of a haemodialysis device as an extracorporeal circuit because no appropriate blood pump was available as a power unit, and the lack of generalisability of the findings.
Bradic et al. (2020)
Key outcomes
All people in the study were having therapy with either ticagrelor (n=19), rivaroxaban (n=12) or dabigatran (n=3). CytoSorb was used in 22 of 34 people, compared with 12 people without adsorption. People without CytoSorb had a longer total surgery time (310 minutes versus 240 minutes), higher average draining volumes in the first 24 hours (1,200 ml versus 320 ml), more transfusions of red blood cells (950 ml versus 250 ml), platelets (800 ml versus 150 ml), and fresh frozen plasma (1,180 ml versus 620 ml). People without CytoSorb also had higher re‑sternotomy rates (58% versus 18%) and longer ICU stays (5.3 days versus 2.4 days).
Recent and ongoing studies
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Ticagrelor CytoSorb hemoadsorption (TISORB). ClinicalTrials.gov Identifier: NCT04131959. Status: recruiting. Indication: cardiothoracic surgery, bleeding. Devices: CytoSorb. Estimated completion date: August 2021. Country: UK.
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Ticagrelor removal study using CytoSorb® 300 ml device during cardiopulmonary bypass in patients undergoing emergent cardiothoracic surgery (CyTation). ClinicalTrials.gov Identifier: NCT04625764. Status: recruiting. Indication: acute coronary syndrome. Devices: CytoSorb. Estimated completion date: January 2022. Country: Germany.