New RCT Hopes to ‘CRACK-IT’ With Aggressive Vessel Prep in Heavily Calcified Fempop Lesions

An introduction to a new trial focused on  aggressive vessel preparation took center stage on Wednesday as part of a ‘last frontiers’ session tackling severely calcified lesions. In his presentation, Tim Wittig (University Hospital Leipzig, Germany) detailed the CRACK-IT trial, which is investigating the role of intravascular lithotripsy (IVL; Shockwave Medical Peripheral Lithotripsy System)—a novel calcium modification procedure that uses sonic pressure waves to modify both intimal and medial calcium within the vessel wall. Similar to urological lithotripsy, the sound pressure waves harmlessly penetrate the soft tissue and break up the calcium, minimizing the risk to the non-calcified parts of the vessel.

LINC Today caught up with Dr Wittig to find out more about this intriguing trial, and the future hopes for IVL in improving vessel preparation.

What was the genesis for the CRACK-IT trial?

In patients with peripheral arterial disease (PAD), the presence of vessel calcification indicates a poorer prognosis and poses a major challenge for endovascular revascularizations. Severely calcified arteries are difficult to dilate with conventional balloon angioplasty and often require mechanical removal and/or modification of plaque with focal force balloons or atherectomy. Atherectomy reduces the need for bailout stenting, but vascular complications including distal atheroembolization remain a significant challenge. 

The aim of the study is to evaluate IVL-based lesion preparation versus conventional balloon angioplasty in extremely calcified femoropopliteal lesions, which are typically not included in clinical trials. At the moment, we do not really have an adequate scoring classification system that reflects these extreme, typically combined intimal and medial calcifications, but such lesions represent a major challenge in clinical routine.

So far, we have mostly treated patients with extremely calcified total occlusions using the pave-and-crack technique. Key elements of this treatment strategy comprise covered stent (VIABAHN, W.L. Gore & Associates) placement into the severely calcified segment, which is afterwards aggressively dilated with high-pressure balloons. Subsequently, the covered stents are relined by interwoven Supera (Abbott) stents, which provide high radial force preventing recoil and restenosis. Of course, many modifications of this technique exist and are used in clinical routine, but aggressive dilatation and interwoven stent implantation are key elements for adequate luminal gain and prevention of recoil to support long-term patency.

In this study, we evaluate the additional value of IVL to potentially reduce dissections, perforations and the need of stenting in these challenging lesions.

Can you run us through the objectives and design of the trial?

The study is an investigator-initiated (principal investigators Andrej Schmidt and Sabine Steiner), prospective, single-center, 1:1 randomized pilot study (120 subjects; 60 per study arm) to evaluate the real-world acute performance of the Shockwave system versus standard treatment with aggressive balloon angioplasty for lesion preparation prior to Supera stent implantation. It is important that the clinical study is independent of industry, but is funded by an independent research institution, the Helmholtz Institute for Metabolism, Obesity and Vascular Diseases.

Patients with symptomatic stenotic or occluded severely calcified lesions in de novo or restenotic superficial femoral artery (SFA) and/or proximal popliteal artery in PAD patients with Rutherford Classification 2–5 will be included. Minimum target lesion length is ≥10 cm with no maximum lesion length limit. All lesions have to exhibit severe calcification on fluoroscopy defined by PACSS Grade 4: 1) bilateral calcification and 2) extending ≥ 50 mm in length. No previous stent in the target lesion is allowed.

Enrollment is expected to take 24 months. All patients will receive subsequent Supera stent implantation at the operator’s discretion. Additional post-dilatation or standard nitinol bare metal stent, drug-eluting stent or covered stent implantation is at the operator’s discretion. All enrolled subjects will be followed up through 60 months. Through 3 years after index procedure the incidence of restenosis will be assessed by duplex ultrasound (DU). Importantly, all angiograms and DU scans will undergo core lab adjudication.

The primary efficacy endpoint is procedural success defined as residual stenosis ≤ 30% without flow-limiting dissection (≥ Grade D) in the final angiogram, and without the need for additional stent implantation. The primary safety endpoint is a composite defined as freedom from device and procedure-related death, freedom from both target limb major amputation and clinically driven target lesion revascularization (TLR) through 12 months post-procedure.

Key secondary endpoints will comprise rate of vessel rupture, need of additional stent implantation and length of stented segments; need of intraprocedural pain medication and patient’s pain perception; fluoroscopy time and radiation dose; primary patency through 36 months, clinically driven TLR and all-cause mortality through 60 months as well as sustained hemodynamic and clinical improvement over time.

How are patients being selected for the trial?

Patients are screened for study inclusion within clinical routine. Over the last years, we see and treat more and more patients with heavily calcified and complex lesions as one of the most challenging patient populations for endovascular treatment. Due to advanced calcification and often poor run-off, bypass surgery is also a challenge and treatment with the pave-and-crack technique is a good endovascular alternative. Importantly, optimal inflow is the key to long-term patency. For ostial SFA lesions, we try not to compromise the origin of the deep femoral artery, as this could be problematic in the event of SFA reocclusion. 

Can you describe the parameters for high-pressure balloon angioplasty in the trial?

Vessel preparation with standard and/or high-pressure balloon angioplasty should be performed with a conventional (non-drug-coated) and/or high-pressure balloon (up to 40 atm) performed in accordance with the device’s instructions for use [IFU] and institutional standard of care. We don’t want a balloon waist during angioplasty indicative of residual stenosis that could not be cracked during ballooning.

Similarly, for the IVL arm, what are the steps, and how do you determine the appropriate level of sonic pressure and number of passes?

A full description of the procedure is detailed in the IFU, which guides on the appropriately sized lithoplasty balloon catheter that should be selected. Once the lithoplasty balloon is placed in the target lesion area, the balloon should be inflated to 4 atm, and lithoplasty treatment delivered for the pre-programmed time of 30 seconds (30 pulses). Note that the generator is programmed to force a minimum pause time of 10 seconds following every 30 pulses delivered.

Following the lithoplasty, the balloon is inflated to the reference size using the balloon compliance chart (as per IFU), and lesion response is recorded on fluoroscopy. Then, the balloon is deflated and a pause of 30 seconds is included to re-establish blood flow.

Operators can repeat the steps above to complete a minimum single treatment of 60 pulses. Additional treatments can be performed if deemed necessary, including moving on to other lesion areas with appropriate modification to balloon catheter size as needed. As we often treat long lesions, these steps can be time-consuming, but are essential for the success of the technique.

What imaging modalities are used to assess the efficacy of vessel preparation and stent deployment?

All treatment decisions are based on angiogram assessments as we do not routinely use intravascular ultrasound (IVUS). In selected cases and clinical scenarios, additional IVUS or extravascular ultrasound can be performed at the operator’s discretion. Post-procedure care includes DU assessment and ankle-brachial index measurements prior to discharge

What is the latest status of the trial?

The study has only recently started as planned, so interim results are not yet available. These will be presented at the following LINC congresses.

What are the potential implications for clinical practice?

If our study results show that IVL is superior to the standard treatment, it should be implemented as a routine treatment for exceptionally long and calcified (and otherwise untreatable) peripheral lesions. As we are currently at the beginning of the study, we are waiting for the first results and are excited to see what new insights this will bring us.