A search of the Medicines and Healthcare Products Regulatory Agency website identified a Consent Decree issued by the US Food and Drug Administration (FDA) for medical devices supplied by Atrium Medical. This applies to the ClearWay RX (Medicines and Healthcare products Regulatory Agency 2015). The FDA has identified problems with quality management systems at Maquet and its subsidiaries (including Atrium Medical). The consent decree requires that Atrium Medical's (Maquet) customers sign a Certificate of Medical Necessity to allow the company to continue supplying these medical devices.
A search of the FDA Manufacturer and User Device Facility Experience database identified 22 records of adverse events related to the ClearWay RX. Some of these followed its use in peripheral vasculature, where the original injury resulted in amputation, and some were associated with the Infuse AMI trial (described in the clinical evidence section). Some of the reports indicate that major acute coronary events (MACE) have occurred when using the device, including cardiac arrest, but causation is unclear. Other events include renal failure, leakage of drug between the balloon and the guidewire, and mechanical problems.
Eighteen studies of potential relevance to the ClearWay RX perfusion balloon catheter were identified, of which 16 were excluded from further assessment:
One study compared intracoronary delivery of eptifibatide via a ClearWay RX catheter with thrombus aspiration using a different type of catheter (Hamza et al. 2014). This was excluded as neither of the control groups had eptifibatide, so any observed effectiveness in the ClearWay RX arm would be confounded by the use of the drug.
There were 11 non-comparative studies (case series) investigating the use of the ClearWay RX to deliver a variety of drugs. However, because there were no comparison groups, these have also been excluded because it would not be possible to distinguish the effect of ClearWay RX from that of the drug it was delivering. In addition, there were 3 randomised control trials listed on the manufacturer's website that had no mention of the use of the ClearWay RX (Svilaas et al. 2008, Thiele et al. 2008, Zhao et al. 1999).
The Infuse AMI trial (Gibson et al. 2011, Stone et al. 2013, 2012, Tomey et al. 2015) was a large randomised controlled trial with 4 arms. The objective of the trial was to demonstrate that administrating an intracoronary bolus of abciximab before stent implantation in patients with anterior STEMI results in reduced infarct size compared with no abciximab bolus. The 4 arms were:
aspiration of the thrombus (blood clot) plus intralesional abciximab (0.25 mg/kg) delivered using a ClearWay RX catheter
aspiration of the thrombus with no intralesional abciximab
no aspiration of the thrombus but with intralesional abciximab (0.25 mg/kg) delivered using a ClearWay RX catheter
no aspiration of thrombus with no intralesional abciximab.
This study was excluded because it does not allow for the comparison of intralesional abciximab delivered by a ClearWay RX catheter with drug delivery by another means.
Two comparative studies (COCTAIL [Prati et al. 2010, 2011] and Crystal AMI trial [Dave 2010]) were identified on the use of the ClearWay RX in coronary arteries and are included in this briefing.
COCTAIL was a randomised controlled trial that took place in coronary care units in Rome and Catania in Italy and Warsaw in Poland (see table 1 for characteristics of the trial). The trial aimed to investigate whether local abciximab delivery to the site of an intracoronary thrombus is more effective than intracoronary bolus infusion in patients with acute coronary syndromes having PCI and downstream clopidogrel administration. The trial included patients with unstable angina, NSTEMI and STEMI having primary PCIs, with a significant lesion in the culprit artery indicative of local thrombus (thrombus score ≥50 according to optical coherence tomography [OCT]). The intervention was abciximab (0.25 mg/kg) given through a ClearWay RX catheter, compared with the same dose of abciximab given through a guide catheter. The primary outcome measure was a change in thrombus burden, as defined by the thrombus score. This was based on the semi-quantitative assessment of thrombus (number of involved quadrants in the cross-sectional OCT images) and the longitudinal extension of the thrombus. Other outcomes included arterial profile, thrombus scores, myocardial blush grade, thrombolysis in myocardial infarction (TIMI) frame count, and clinical events at 30 days and 1 year. The sample size was 50 patients, with 25 in the ClearWay RX arm and 25 in the control arm. There were no differences in the baseline characteristics between the 2 groups including demographic or previous medical history factors. The results showed no significant differences between the 2 groups for the primary outcome measure of thrombus score (ClearWay RX group mean score 68.8 (standard deviation [SD] 44.8), control group mean score 85.4 (SD 52.7, p=0.393). However, there were statistically significant improvements for the ClearWay RX group in the extent of stenosis of the target artery, TIMI frame count, procedure-related myocardial infarctions and major adverse coronary events at 1 year (see table 2). There were no statistically significant differences between the 2 groups in mean myocardial blush grade and the number of target lesion revascularisations at 1 year. The authors concluded that local intracoronary delivery of abciximab through a ClearWay RX catheter markedly reduces thrombus burden, with the potential to improve coronary microcirculation and reduce major event rates.
The Crystal AMI trial (Dave 2010) was reported in a conference presentation only and does not appear to have been published. The lead author was contacted but no further information was available. Crystal AMI was described as a proof-of-concept trial that was not powered to show statistical differences. It was a single-centre randomised controlled trial in patients with STEMI within 6 hours of symptom onset (see table 3). The intervention was intracoronary abciximab via a ClearWay RX catheter and control was intravenous abciximab. Follow‑up was to 30 days. The primary outcome was TIMI myocardial blush grade, and other outcomes included TIMI flow, ST resolution, left ventricular function at hospital discharge, readmissions and deaths. The results for TIMI myocardial blush grade >2 were 92% in the intervention group and 87% in the control group. No statistical significance estimates were given so it is unclear whether any of the outcomes were statistically significantly different. The author's conclusions were that intracoronary abciximab via a ClearWay RX catheter is safe and effective, and produced higher myocardial blush grade scores and a trend towards higher ST-segment resolution.
One ongoing trial on the ClearWay RX for coronary artery thrombus dissolution was identified. The protocol for this study is published (Prati et al. 2013) and 2 abstracts with results were found (Gatto et al. 2014a, 2014b). Neither of the abstracts gave results attributable to the intervention group.
In the COCTAIL trial (Prati et al. 2010, 2011), a clear hypothesis was evaluated in terms of the patients included, and the intervention and control used. The randomisation schedule was devised and implemented by the study statistician. It was an open-label trial so there was no allocation concealment. Patients were analysed in the groups to which they were assigned, but not all patients were accounted for in the outcomes assessment (5 were excluded from the ClearWay RX group and 4 from the control group). However, reasons for exclusion were given. In the ClearWay RX group, the reasons were insufficient OCT image quality (n=3), wrong segment matching (n=1) and thrombus score >50 (n=1). In the control group the reasons were insufficient image quality (n=3) and wrong segment matching (n=1). It would have been very difficult to blind the investigators because of the use of different equipment in the 2 groups during the procedure. There was no mention of blinding of patients or outcome assessors. The 2 groups were similar at the start of the trial for a wide variety of potentially confounding factors, and except for the interventions it appears that both groups were treated in a similar way. The sample size calculation estimated that 40 patients would need to be enrolled to achieve a 25% difference in the primary end point. This is a large difference and was not seen in the results. It is likely that a small difference would not be seen, so a suitably powered trial would need to include several hundred patients. The patients in the trial were from 2 European countries so the results are likely to be generalisable to patients treated within the NHS.
The Crystal AMI trial (Dave 2010) is reported only as a conference presentation so there are very few details about how the trial was done. A clear question was evaluated in terms of the patients included, and the intervention and control used. No details of the method of randomisation are given and the presence of allocation concealment is unclear. It is assumed that follow‑up was completed and that patients were analysed in the groups to which they were randomised. It would be very difficult to blind the investigators because of the use of different equipment in the 2 groups during the procedure. There was no mention of blinding of patients or outcome assessors. The 2 groups were similar at the start of the trial for a variety of potentially confounding factors such as age, gender, symptoms, prior intracoronary procedures, diabetes, smoking status and blood lipid profile. Apart from the interventions, it is unclear whether both groups were treated in a similar way. There was no sample size calculation given but the trial was described as a proof of concept that was not powered to show statistical differences, and no statistical significance estimates were given, so it is unclear whether any of the outcomes were statistically significantly different. Patients were from USA, so it is unclear if the results are generalisable to NHS practice.