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One-Year Results From COMPARE Trial Presented at LINC

Drug-Coated Balloon Data

One-Year Results From COMPARE Trial Presented at LINC

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Contributed by LINC Today/MediFore LTD (www.MediFore.co.uk)

01/28/2020

(Leipzig, Germany) January 28, 2020 -- One-year results from the COMPARE trial were showcased on the first morning of LINC, shedding new light on the impact of high- vs low-dose paclitaxel dosing in drug-eluting balloon (DCB) treatment of femoropopliteal disease. Presentation of the first-time data came on the same day as publication of the results online in the European Heart Journal.1

The COMPARE trial is a prospective, multicenter, non-inferiority clinical trial of 414 patients with symptomatic femoropopliteal lesions (Rutherford classification 2–4) randomly assigned in a 1:1 ratio to endovascular treatment with either the low-dose (2.0 μg/mm2) Ranger DCB (Boston Scientific) or high-dose (3.5 μg/mm2) IN.PACT Admiral or Pacific DCBs (Medtronic). Patients were stratified according to lesion length (10 cm, >10 cm and 20 cm, >20 cm and 30 cm) in order to ensure inclusion of a relevant proportion of complex lesions.

Talking through the results of COMPARE was Sabine Steiner, MD (University Hospital Leipzig), who introduced the genesis of the trial. “Currently marketed DCBs have been designed based on a similar functional concept using paclitaxel as the active drug, together with an excipient to facilitate the release and transfer of the drug to the vessel wall,” she said. “Besides drug dose, the drug and excipient formulations used in their coatings, and the manner in which coatings are applied to the balloons, differ between commercially available DCBs.”

The coating technology and formulation of the active drug may affect the extent of drug delivery and clinical efficacy, she added, particularly the dosing of paclitaxel which could have a relevant impact on the antiproliferative capacity of these devices.

“Comparability between trials is limited as lesion characteristics and bailout stenting rates differ substantially,” continued Dr Steiner, “and it is unclear thus far if heterogeneity between DCBs translates to meaningful clinical differences. Prior meta-analyses2,3 have suggested such an effect: reduced restenosis and target lesion revascularisation (TLR) rates were suggested for high-dose DCBs based on these analyses.”

COMPARE was born out of the realization that comparative effectiveness of high- vs low-dose DCBs has not been tested within a clinical trial. Its primary efficacy and safety endpoints comprised of primary patency and freedom from major adverse events (ie, device and procedure-related deaths through one month, major amputations, and clinically driven target lesion revascularization through 12 months).1 A non-inferiority margin of −10% at 12 months was set.

Total occlusions were observed frequently (>40%) and provisional stenting was performed in every fourth intervention, noted Dr Steiner. Non-inferiority was determined for both primary efficacy and safety endpoints at 12 months. Patient demographics included a mean age of 68 years, around two-thirds male, one-third diabetics, and current smoking in over 40% of patients. Mean lesion length was >12 cm, with around 40% incidence of chronic total occlusions (CTOs). Calcification Grade 3 or 4 according to peripheral arterial calcium scoring system (PACSS) criteria was present in >50% of lesions.

Dr Steiner shared the results: “Procedural success was observed in 96% of patients, defined as residual diameter stenosis of ≤50% determined by angiographic core laboratory, without device malfunction and without procedural complications.

“The primary efficacy and safety endpoint met non-inferiority.1 Primary patency was 81.5% in the high-dose and 83.0% in the low-dose DCB group (difference: 1.5% [lower bound of the 90% two-sided confidence interval {CI} -5.2%]; Pnon-inferiority <.01). Freedom from major adverse events was determined in 92.6% of the high-dose and in 91.0% of the low-dose DCB groups (difference -1.6% [lower bound of the 90% two-sided CI -6.5%]; Pnon-inferiority <.01).

“Overall death rate was low (2.0%) and no major amputation occurred.”

Briefly touching upon the limitations of COMPARE, Dr Steiner noted that the study was solely designed to assess non-inferiority for primary patency and a combined safety endpoint, but not for functional outcomes. What’s more, use of dedicated lesion-modifying devices was discouraged by the study protocol, but these therapeutic options are commonly used in clinical routine, thereby limiting generalisability of study results. “A general shortcoming of DCB- and other peripheral device trials is the lack of blinding of the operator who is responsible for all procedure-relevant decisions,” she added.

Turning back to the outcomes of COMPARE, Dr Steiner reiterated its take-home messages: “This was the first head-to-head comparison of two DCBs with different paclitaxel dosages and coating technologies for femoropopliteal interventions. Both the low-dose DCB (Ranger 2.0 μg/mm2 ) and high-dose DCB (IN.PACT 3.5 μg/mm2) showed excellent primary patency and low TLR rates, and the primary endpoints for non-inferiority were met.

“Low mortality [was seen] at 1 year. Follow-up is now ongoing for up to five years.”

 

References

1. Steiner S, Schmidt A, Zeller T, et al. COMPARE: prospective, randomized, non-inferiority trial of high- vs. low-dose paclitaxel drug-coated balloons for femoropopliteal interventions. European Heart Journal: ehaa049. https://doi.org/10.1093/eurheartj/ehaa049.

2. Caradu C, Lakhlifi E, Colacchio EC, et al. Systematic review and updated meta-analysis of the use of drug-coated balloon angioplasty versus plain old balloon angioplasty for femoropopliteal arterial disease. J Vasc Surg. 2019; 70(3): 981-995.e10.

3. Katsanos K, Spiliopoulos S, Paraskevopoulos I, et al. Systematic Review and Meta-analysis of Randomized Controlled Trials of Paclitaxel-Coated Balloon Angioplasty in the Femoropopliteal Arteries: Role of Paclitaxel Dose and Bioavailability. J Endovasc Ther. 2016; 23(2): 356-370.

 

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