Clinical and technical evidence

A literature search was carried out for this briefing in accordance with the 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

Six studies are summarised in this briefing: 2 randomised trials, 2 retrospective non-comparative studies and 2 prospective non-comparative studies. The 6 studies involved 381 patients, 274 of whom had DyeVert (9 had DyeVert Power XT, 173 had DyeVert Plus and 92 had DyeVert [that is, it did not specify which type of DyeVert system was used]). Included studies were done in Germany, Australia, US and Italy. These studies used DyeVert in coronary angiogram or percutaneous coronary intervention procedures.

Table 1 summarises the clinical evidence as well as its strengths and limitations.

Overall assessment of the evidence

There is limited high-quality published evidence on DyeVert. Only 2 of the included studies involve a comparator, making it difficult to conclude the efficacy of DyeVert compared with standard care. One of the included studies (Bruno et al. 2019) used the DyeVert Power XT device with an ACIST power injector, to allow for use with power contrast injections. Sample sizes are relatively small and there is no published UK evidence.

There is a need for larger prospective, UK-based, multicentre, randomised controlled trials using DyeVert compared with standard care. Important outcomes would include how the contrast media volume savings from DyeVert affect rates of contrast-induced acute kidney injury (CI‑AKI), with follow up long enough to detect this, to see the device's efficacy at preventing this complication.

Table 1 Summary of selected studies

Bruno et al. (2019)

Study size, design and location

A single-centre retrospective pilot study involving 9 patients having diagnostic or interventional invasive coronary angiography over 2 consecutive days in November 2018.

Location: Germany.

Intervention and comparator(s)

Intervention: DyeVert Power XT System and ACIST CVi Contrast Delivery System (n=9).

Comparator: None.

Key outcomes

The average volume of CM delivered to patients was 80.6 ml (range 45.5 ml to 211.9 ml). Attempted delivery was 127.8 ml (range 71.6 ml to 304.9 ml), resulting in average CM savings of 38.9% (range 31.0% to 47.0%). Ratio of total CM volume to creatinine clearance was reduced from 1.84 (attempted approach, array 1.03 to 4.41) to 1.12 (delivered approach, array 0.73 to 3.04). There were no DyeVert Power XT system failures. A physician assessment results and reported no loss of angiograph quality.

Strengths and limitations

Four different physicians did the procedure and used the device, helping to reduce potential bias. No statistical analysis of results. Small sample size. Coexisting use of device with ACIST power injector, uncertain over the efficacy of DyeVert with other power injectors. No random allocation and no control group. Reduced contrast media dose was estimated, and subjective unblinded assessment of image quality by the physicians may have introduced bias. Not in UK so may not be generalisable to the NHS. Author reports to have received speaking fee from company.

Desch et al. (2018)

Study size, design and location

A prospective, single-centre, open-label randomised controlled trial of 96 patients having diagnostic coronary angiography from April 2016 to May 2016.

Location: Germany.

Intervention and comparator(s)

Intervention: DyeVert with standard care for diagnostic coronary angiograms (n=48).

Comparator: Standard diagnostic coronary angiogram (n=48).

Key outcomes

There was a 41.0% reduction in CM volume in DyeVert group compared with comparator group (36.9±10.9 ml versus 62.5±12.7 ml, p<0.001). Image quality using DyeVert system was not inferior compared with control (p=0.03). There were no device-related adverse events.

Strengths and limitations

A randomised controlled trial is good-quality evidence. Randomisation method was permuted block randomisation stratified by access site using a computer to generate random numbers, to prevent bias. However, physicians doing the procedures were aware of randomisation results and blinding was not possible because of visual differences with the tubing set. Image quality assessment was done by independent reviewer who was blinded to treatment allocation. Study was powered for primary (different in CM volume) and secondary (image quality) end points, but not for incidence of serious adverse device effects. The study was not in the UK so may not be generalisable to the NHS. Study sponsored by the company. Author is a consultant to the company.

Sapontis et al. (2017)

Study size, design and location

A multicentre prospective, single arm clinical pilot study involving 44 patients having coronary diagnostic or PCI procedures.

Location: Australia and Germany.

Intervention and comparator(s)

Intervention: DyeVert system (n=44).

Comparator: None.

Key outcomes

The mean CM volume attempted to be injected versus actual volume injected were 173±117 ml versus 89±57 ml respectively. The mean volume saved by DyeVert was 47% (p<0.0001). Mean volume savings were similar for diagnostic (47±9%) and PCI (50±9%) procedures (p=0.26). Image quality was good in 43 out of 44 patients (98%). In 1 patient, the clinician judged image quality to have a "washed out appearance" and so DyeVert was turned off for 2 injections. Clinician-rated device acceptability was high (95% to 98%).

Strengths and limitations

Power calculation performed to calculate sample size. Patients who, in the investigator's opinion DyeVert was not appropriate for, were excluded. This is subjective and may have introduced bias. Subjective assessment of image quality by the clinician doing the procedure, which is unblinded and prone to bias. No comparator to compare outcomes with standard care. The CM used varied, which may have affected results. One of the authors is a consultant to the company. The company was the contract grant sponsor.

Gurm et al. (2018)

Study size, design and location

A prospective, multicentre, single-arm observational study enrolling 114 patients (105 patients in primary end point analysis, 114 patients in secondary end point analysis) having diagnostic coronary angiogram or PCI procedures done with manual injections between July 2017 to December 2017.

Location: US.

Intervention and comparator(s)

Intervention: DyeVert Plus System.

Comparator: None.

Key outcomes

Mean CM volume attempted was 112±85 ml (range 22 ml to 681 ml) and mean CM volume given was 67±51 ml (range 12 ml to 403 ml), resulting in overall CM volume savings of 40.1±8.8% (95% CI 38.4 to 41.8; p<0.0001) per procedure. Image quality was maintained in 104 patients, with 1 patient having the system turned off for 1 injection. No adverse events were reported. AKI was reported in 11 patients, with 7 in patients with baseline eGFR less than 30 ml/min/1.73 m2. There were 3 AKI cases attributed to CM. There were significant differences in contrast savings for subgroups defined by BMI (p=0.0398) and procedure type (p=0.0057). Contrast savings were also significantly different between different physicians (p=0.0029). At lower CMV/eGFR ratios, DyeVert Plus increased the percentage of subjects with ratios of 1 or lower from 7% (attempted) to 33% (actual) and with ratios of 2 or lower from 42% (attempted) to 75% (actual). Conversely, at higher CMV/eGFR ratios, DyeVert Plus reduced the percentage of subjects with ratios of more than 2 from 58% (attempted) to 25% (actual). Observed AKI rates increased with increasing CMV/eGFR ratios, with no patients with a CMV/eGFR ratio of less than 1 developing AKI. Catheter laboratory staff reported DyeVert Plus system setup and priming added 3.3±2.9 minutes to procedure preparation time. 55% (63 patients) were discharged on the same day. 17% (19 patients) were discharged 3 or more days after the procedure.

Strengths and limitations

Multicentre trial with procedures performed by 17 different interventional cardiologists helps to reduce bias. Reasonably good sample size which was powered to detect CM volume savings of 35%±16%. Good range of outcomes including rates of CI-AKI. However, study states that data on rates of CI-AKI should be 'hypothesis-generating' as post-procedure laboratory data were not available for all patients, suggesting that results may not be accurate or generalisable to real-life practice. No comparator group means no comparison to standard of care. The type of CM, and use of other renal protection strategies such as hydration and discontinuation of medications, were at discretion of study investigator. This makes it difficult to attribute changes in outcomes to DyeVert. CM saved was the value shown on the DyeVert contrast monitoring system, with no quality assurance comparator to check accuracy. Study sponsored and funded by the company. Of the authors, 2 are consultants for the company and 1 received research funding from the company.

Corcione et al. (2017)

Study size, design and location

A retrospective analysis of 10 patients having coronary or peripheral invasive procedures from an institutional clinical database when DyeVert Plus was used.

Location: Italy.

Intervention and comparator(s)

Intervention: DyeVert Plus (n=10).

Comparator: None.

Key outcomes

All procedures were completed with adequate and high-quality angioscopic and angiographic images. One patient had CI-AKI. Mean CM volume was 79.9±48.8 ml (95% CI 53.2 to 109.4), with a mean absolute saving of 55.8±31.9 ml (95% CI 39.1 to 76.7, p<0.05), and a relative saving of 41.8±7.3% (95% CI 37.5 to 46.4, p<0.05). The mean theoretical total CM volume was 135.7 ml (95% CI 95.2 to 186.7). Comparison of CM volume estimates between DyeVert Plus versus manual measurements showed a mean absolute difference of −1.6 ml (95% CI −2.9 to −0.4, p<0.05) and a relative difference of −1.9% (95% CI −3.5 to 0.2, p>0.05).

Strengths and limitations

Statistical analysis of results, with a good range of outcomes. Procedures are as per device indications, meaning results are generalisable to the target population. Different types of CM used, which may have affected results, so outcomes are difficult to attribute solely to DyeVert. Very small sample size limits reliability of study findings. Not in UK so may not be generalisable to an NHS setting. Retrospective observational study which is low quality evidence.

Bath et al. (2019)

Study size, design and location

A randomised study involving 108 patients at increased risk of CI-AKI having diagnostic angiography with or without DyeVert Plus.

Location: US.

Intervention and comparator(s)

Intervention: Diagnostic angiography with DyeVert Plus (n=49).

Comparator: Diagnostic angiography without DyeVert Plus (n=59).

Key outcomes

When comparing DyeVert Plus arm with standard of care arm, mean cumulative CM volume was 62.7±9.5 ml (95% CI) versus 87.6±110 ml (95% CI) respectively, resulting in a 28.4% (p=0.0004) reduction in CM volume with DyeVert Plus. CM given through DyeVert Plus was 43.8% below the threshold volume (eGFR ×3) for the cohort as compared to 31.4% in the standard of care arm (p=0.05). Contrast savings of 34.9±3.0% (95% CI) were seen in the DyeVert Plus arm.

Strengths and limitations

Randomised study design helps to reduce bias and allows comparison of outcomes to standard of care. Relatively good sample size. Abstract from a poster presentation is low-quality evidence and lacks details of study methodology. There is no information regarding baseline characteristics, how study participants were selected, how they were randomised and whether there was any loss to follow up. Outcomes such as image quality were not assessed. Not in UK so not generalisable to an NHS setting.

Abbreviations: AKI, acute kidney injury; BMI, body mass index; CI, confidence interval; CM, contrast media; CMV, contrast media volume; PCI, percutaneous coronary intervention; eGFR, estimated glomerular filtration rate.

Recent and ongoing studies

The company states that UK-based evidence about contrast use and clinician satisfaction data is pending publication.