The device met the primary endpoint of non-inferiority for safety and efficacy against MitraClip in degenerative MRI patients.
BOSTON, MA — Patients with severe degenerative mitral valve regurgitation (MR) are not eligible for surgery as well when treated with the Pascal Device (Edwards Lifesciences) as those treated with the MitraClip (Abbott), according to the CLASP IID study.
The results, which were presented as a recent clinical trial at TCT 2022 and simultaneously published in JACC: Cardiovascular InterventionsCome on, just two days after the US Food and Drug Administration agreed Pascal’s Edge-to-Edge Repair (TEER) System for Degenerative Magnetic Resonance Therapy, making it the second device available in the United States.
“The CLASP IID trial is the first randomized controlled trial to directly compare two TEER treatments and also demonstrate the safety and efficacy of the mitral valve in patients with degenerative mitral reflux disease with elevated surgical risks,” said study researcher Konstantinos Kologianis, MD (Atlantic). Health System Medical Center (Morristown, NJ), during a press conference. “It met the essential endpoints for safety and efficacy, with the Pascal system showing low compound major adverse events and a significant and sustained reduction in MRI.”
Scott Lim, MD (University of Virginia Health System Hospital, Charlottesville, VA), said introducing a second device is important, because it provides doctors and patients options.
“The two devices have different design features that I think may be useful in different anatomy,” Lim said.
For example, Pascal’s hollow nitinol frame construction allows it to be passively closed and flexed during systole and diastole. The device also lengthens, Lim said, allowing it to be maneuvered into dissecting denser coronary tendons. The clamps for holding the coronal leaflets can be operated side by side or independently, allowing the leaflet to be picked up in stages and adjusted, and the central spacer helps close the fitting gap so that the leaflets are not pulled together too tightly.
Federico Asch, MD (MedStar Health/Georgetown University, Washington, DC), who was not involved in CLASP IID, congratulated the researchers, saying the field has now entered a new era. “We have built a lot of data using MitraClip as a device, but as a composite it is now important to show that TEER works. There will be patients who are the best candidates for one. [device] or else. I don’t think we have that answer now,” he said.
Speaking with TCTMD, Janarthanan Sathananthan, MBChB (University of British Columbia/Vancouver General Hospital/St Paul’s Hospital, Vancouver, Canada), who was not involved in the study, echoed Ash’s comments.
“I think it helps to have another device that offers TEER as an option,” he said. “We have seen the difficulties with TMR screening. We have high exclusion rates, so having another device that offers an edge-to-edge repair treatment option is beneficial. CLASP IID also enhances the benefits of edge-to-edge repair”
Interim analysis of 180 patients
The CLASP IID study included 180 patients enrolled at 43 sites in the United States, Canada and Europe between 2018 and 2021. Up to 300 patients are scheduled to be enrolled. However, interim analyzes of 180, 210 and 240 patients were planned provided that the sample size was sufficient for primary endpoint analysis. In 180 patients, the interim analysis continued because the predictive probability of study success exceeded 96.5%, the researchers say.
The current analysis included 117 patients treated with Pascal and 63 treated with MitraClip, the most common reason being that patients in both treatment groups were ineligible for surgery. Both were well matched, but those who received the Pascal device were more likely to have had previous aortic valve surgery, or TAVI. Two-thirds of patients received a Pascal implant; And 24.1% got the newer Pascal Ace, which is narrower, shorter, and has longer clamps; and 8.6% obtained a combination. In the MitraClip arm, 39.3% treated with the NT/NTR/XTR device while 60.7% received the newer-generation G4 device, which contains independent clips to hold the coronary leaflets.
With regard to the major adverse events—a composite safety endpoint that included cardiovascular death, stroke, myocardial infarction, need for renal replacement therapy, severe bleeding, and non-selective mitral re-intervention—Pascal’s system met the margin of non-inferiority when compared to the MitraClip (3.4 %) with Pascal versus 4.8% with MitraClip). At 30 days, the 1.3% difference in major adverse events had a one-sided higher confidence limit of 5.1%, which is within the predefined non-inferiority margin of 15%.
With Pascal, there was one cardiovascular death, three acute haemorrhages, and mitral valve re-intervention. In the MitraClip group, there was one cardiovascular death and two severe bleeding.
In terms of efficacy, the proportion of patients with an MR ≤ 2+ at 6 months was 96.5% with Pascal and 96.8% with MitraClip. An absolute difference of 0.3% had a one-sided low confidence limit of 6.2%, which is within the pre-specified non-inferiority margin of 18%. Regardless of the device, all patients had an MR ≤ 2+ at discharge while 87.2% and 88.5% of the Pascal- and MitraClip-treated patients had an MR ≤ 1+ at discharge. At 6 months, 83.7% of patients treated with Pascal and 71.2% of patients treated with MitraClip had an MR ≤ 1+, indicating “some loss of efficacy during the same follow-up course” with MitraClip, according to MitraClip. investigators. Mean valve gradients were stable over time in both groups.
Commenting on this reference, Lim told TCTMD: “This is clearly only 6 months, only 180 patients… We have to see if this affects the whole group over a much longer follow-up range. If it is, I think it’s something Operators will be taken into account. This is reflected in at least two other publications outside Europe when comparing [Pascal] to MitraClip, [they] It appears to have found reduced efficacy with MitraClip patients. It might pay off, but it’s still a little early to say so.”
Satananthan noted that CLASP IID has limitations, most notably low patient numbers. However, the second device, which appears to have a lower MR residual than that seen with the MitraClip, is a valuable addition. For TCTMD, Sathananthan said one of the puzzles faced by the operators who carried out the overhaul was that the severity of MR could be underestimated immediately after the procedure. Then, upon follow-up, it is not uncommon for the MR to be slightly higher than expected.
“So, that continuous benefit [with Pascal] promising,” describing it as a sign worth seeing in a larger group and on long-term follow-up. “It is good to try to get the results of a surgical-like repair in the end. All this is positive for the field.”
Quality of life and functional outcomes
Patients in both treatment arms had significant improvements in functional ability and quality of life when compared to baseline, but there was no difference between devices. Action times were longer with the Pascal device (88 vs 79 min), but decreased over time, indicating a small learning curve with the device. The researchers noted that most of the participating sites had no prior experience using the Pascal device prior to the CLASP IID.
One of the advantages of the MitraClip is how experienced the operator is, Lim said, noting that operators may lean toward it because they are comfortable implanting it. In terms of anatomy, he said, more complex or thicker mitral posts requiring mechanical closure might also be suitable for a MitraClip.
The entire trial has completed registration and patients are currently being followed up. Lim said they hope to provide data from the full cohort of 300 patients early next year.
The Pascal system has CE Mark certification in Europe for both MRI and tricuspid regurgitation.