Covered CP Stents for the Prevention or Treatment of Aortic Wall Injury Associated With Coarctation of the Aorta (COASTII)

Covered CP Stents for the Prevention or Treatment of Aortic Wall Injury Associated With Coarctation of the Aorta

Covered Cheatham Platinum Stents for the Prevention or Treatment of Aortic Wall Injury Associated With Coarctation of the Aorta

Coarctation of the aorta (CoA) is a congenital abnormality producing obstruction to blood flow through the aorta. Coarctation can occur in isolation, in association with bicuspid aortic valve or with major cardiac malformations. CoA accounts for 5-8% of the 8/1000 (4-6/10,000) children born with congenital heart disease. Most CoA is newly diagnosed in childhood; < 25% recognized beyond 10 yrs. CoA is mostly repaired in childhood by surgery or by balloon catheter dilation. Recurrence rates range from 5-20%. Recurrence is often not recognized until adolescence. Balloon expandable stents have become the predominant therapy in the USA and Europe for CoA treatment in this age group. There are no FDA approved stents for this use. Biliary stents are currently being used off label. Enrollment into a trial of bare metal Cheatham Platinum (CP) Stents, designed for use in CoA, is completed. The Coarctation of the Aorta Stent Trial (COAST) aims to confirm safety and efficacy of CP Stent for native and recurrent CoA. There are CoA patients with clinical situations that place them at high risk of aortic wall injury during bare metal stenting. Extreme narrowing, genetic aortic wall weakness and advanced age are examples. Patients may present with aortic wall injury (aneurysm) related to prior CoA repair. The occurrence after surgical repair is 3-4% and after balloon dilation 10-20%. Repair of these aneurysms is surgically challenging. The use of fabric-covered CP Stents to prevent or repair aortic wall injury has become the treatment of choice in Europe and recently in the US through the FDA Compassionate Use process. There are no alternative devices available in the US. COAST II will test safety and efficacy of Covered CP Stents to repair or prevent aortic wall injury associated with CoA. Funding Source-FDA OOPD

There are no prior trials of preventing or treating aortic injury associated with CoA and thus no basis for comparison. A single outcome assessment will not suffice since patients can receive a device for either indication. A 3-category Severity of Illness Scale (SIS) was developed based on clinical judgment of a panel of pediatric cardiologists and reviewed by a Data & Safety Monitoring Board (DSMB) and the FDA Office of Device Evaluation. Five levels of severity have been defined for each of the 3 illness categories, including: Upper extremity hypertension, Upper to lower extremity pressure difference, and Severity of aortic wall injury. The DSMB will assign a level of illness from the SIS for each patient at baseline and one year follow up. Improvement by at least one level will indicate clinical importance. Safety is evaluated by identifying adverse events and comparing their occurrence to surgical repair of CoA in similar age groups reported in the medical literature.

A Cheatham covered platinum stent will be implanted in the Descending aorta to repair coarctation of the aorta in qualified patients.

Study Participants With Grade 4 or 5 in Degree of Aortic Wall Injury (AWI) and/or Aortic Arch Obstruction Without Clinical Worsening

Severity of Illness Scale (SIS) improvement increase of at least 1 grade from baseline to 12 month follow-up SIS is divided into 3 conditions & 5 grades of severity: 1 = worst (reserved for AWI) , 5 = best) C1 Upper Extremity Systolic Blood Pressure (SBP) 2- > 159 mmHg or any hpn on >2 medications 3- 140-159 mmHg or elevated SBP on >2 medications 4- 130-139 mmHg or normal SBP on >2 medications 5- <130 mmHg on 0-2 meds C2 Upper Extremity to Lower Extremity SBP difference 2- >59 mmHg 3- 30-59 mmHg 4- 15-29 mmHg 5- <15 mmHg C3 Aortic Wall Injury severity levels: Uncontained rupture or large aneurysm Contained rupture or stable large aneurysm Small contained rupture or moderate aneurysm Acute, but stable AWI or small aneurysm No injury or minor aortic wall irregularity not in need of treatment. Grades for conditions represent comparable degrees of illness (0 worst, 5 best) -Grade 0 denotes death related to coarctation or study therapy

Secondary Efficacy Outcomes At One Year: (A) Number of participants with arm-leg systolic blood pressure (SBP) differences <15 mmHg and (B) Number of participants with normal or only mildly elevated SBP, no more than mild arm-leg SBP, no clinically significant residual aortic wall injury AND no worsening in any of these three categories

Secondary Safety Outcomes The proportion of patients experiencing any serious or somewhat serious adverse event related to the stent or implant procedure by 24 months follow up, such as: new aortic wall injury within the region of covered CP Stent implantation, stent malposition, stent fracture, aortic wall aneurysms (early or late), or restenosis requiring reintervention, arterial access site injury, bleeding, etc.

Inclusion Criteria: Inclusion criteria for use of a Covered CP Stent: Native or recurrent aortic coarctation* associated with ONE OR MORE of the following: Acute or chronic aortic wall injury, or Nearly atretic descending aorta to 3 mm or less in diameter, or Genetic Syndromes associated with aortic wall weakening. Individuals with genetic syndromes such as Marfan Syndrome, Turner's Syndrome or familial bicuspid aortic valve and ascending aortic aneurysm The significance of aortic obstruction is left to the judgment of the participating investigator. indications might include mild resting aortic obstruction associated with: Exercise related upper extremity hypertension; Severe coarctation with multiple and/or large arterial collaterals; Single ventricle physiology Left ventricular dysfunction Ascending aortic aneurysm + Aortic wall injury might include: Descending aortic aneurysm Descending aortic pseudo-aneurysm Contained aortic wall rupture Non-contained rupture of the aortic wall Exclusion Criteria: Patient size too small for safe delivery of the device. The absolute lower limit for inclusion under this protocol is 20 kg. However, serious femoral artery injury can occur in small patients, particularly those in the 20-30 kg range and this risk must be reviewed in detail with parents or guardians of children in this weight range. Planned deployment diameter less than 10 mm or greater than 22 mm Location requiring covered stent placement across a carotid artery* Adults lacking capacity to consent Pregnancy crossing or covering of a subclavian artery is acceptable in certain situations, but only after alternative treatments have been considered.

Holzer RJ, Gauvreau K, McEnaney K, Watanabe H, Ringel R. Long-Term Outcomes of the Coarctation of the Aorta Stent Trials. Circ Cardiovasc Interv. 2021 Jun;14(6):e010308. doi: 10.1161/CIRCINTERVENTIONS.120.010308. Epub 2021 May 27.