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

• Sponsor: Richard E. Ringel (Other)
• Overall Status: Completed
• CT.gov ID: NCT01278303
• Collaborator: Harvard University (Other)
• Enrollment: 82
• Locations: 19
• Arm: 1
• Duration (Months): 53
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Aortic Coarctation	Device: Treatment of Aortic Wall Injury	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Covered Cheatham Platinum Stents for the Prevention or Treatment of Aortic Wall Injury Associated With Coarctation of the Aorta
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Other: Treatment of Aortic Wall Injury Repair of aortic wall injury with covered CP Stents	Device: Treatment of Aortic Wall Injury; A Cheatham covered platinum stent will be implanted in the Descending aorta to repair coarctation of the aorta in qualified patients.

Outcome Measures

Primary Outcome Measures

1. Study Participants With Grade 4 or 5 in Degree of Aortic Wall Injury (AWI) and/or Aortic Arch Obstruction Without Clinical Worsening [Baseline and 12 months]

   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 Outcome Measures

1. Secondary Efficacy Outcomes - 1 Year [1 years]

   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

2. Secondary Safety Outcomes - Adverse Events [2 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:Inclusion criteria for use of a Covered CP Stent:

Native or recurrent aortic coarctation*associated with ONE OR MORE of the following:

1. Acute or chronic aortic wall injury, or

2. Nearly atretic descending aorta to 3 mm or less in diameter, or

3. 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, or

4. Advanced age. Men and woman aged 60 years or older.

• 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:

1. 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.

2. Planned deployment diameter less than 10 mm or greater than 22 mm

3. Location requiring covered stent placement across a carotid artery*

4. Adults lacking capacity to consent

5. Pregnancy

• crossing or covering of a subclavian artery is acceptable in certain situations, but only after alternative treatments have been considered.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rady Children's Hospital and Health Center	San Diego	California	United States	92123
2	University of California, San Francisco	San Francisco	California	United States	94143
3	Children's National Medical Center	Washington	District of Columbia	United States	20010
4	Miami Children's Hospital	Miami	Florida	United States	33155
5	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30322
6	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
7	Boston Children's Hospital	Boston	Massachusetts	United States	02115
8	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
9	Mayo Clinic	Rochester	Minnesota	United States	55905
10	Children's Hospital of New York - Presbyterian	New York	New York	United States	10032
11	Duke University	Durham	North Carolina	United States	27710
12	Cincinnati Children's Hospital and Medical Center	Cincinnati	Ohio	United States	45229
13	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
14	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
15	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
16	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15213
17	Children's Medical Center Dallas	Dallas	Texas	United States	75235
18	Baylor College of Medicine, Texas Children's Hospital	Houston	Texas	United States	77030
19	Children's Hospital and Regional Medical Center, Seattle	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Richard E. Ringel
• Harvard University

Investigators

• Principal Investigator: John Moore, MD, Rady Children's Hospital
• Principal Investigator: John F Rhodes, MD, Nicklaus Children's Hospital f/k/a Miami Children's Hospital
• Principal Investigator: Thomas Jones, MD, Seattle Children's Hospital
• Principal Investigator: Lisa Bergersen, MD, Boston Children's Hospital
• Principal Investigator: Julie A Vincent, MD, Children's Hospital of New York-Presbyterian
• Principal Investigator: Allison Cabalka, MD, Mayo Clinic
• Principal Investigator: Henri Justino, MD, Baylor College of Medecine, Texas Children's Hospital
• Principal Investigator: Thomas Forbes, MD, Children's Hospital of Michigan
• Principal Investigator: Jonathan Rome, MD, Children's Hospital of Philadelphia
• Principal Investigator: Joshua Kanter, MD, Children's National Research Institute
• Principal Investigator: Phil Moore, MD, University of California, San Francisco
• Principal Investigator: Russel Hirsch, MD, Children's Hospital Medical Center, Cincinnati
• Principal Investigator: Jacqueline Kreutzer, MD, University of Pittsburgh
• Principal Investigator: Thomas Zellers, MD, Children's Medical Center Dallas
• Principal Investigator: Lourdes Prieto, MD, The Cleveland Clinic
• Principal Investigator: Gregory Fleming, MD, Duke University
• Principal Investigator: Dennis Kim, MD, Children's Healthcare of Atlanta
• Principal Investigator: John Cheatham, MD, Nationwide Children's Hospital
• Principal Investigator: Gregory A Fleming, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Richard E. Ringel, Associate Professor of Pediatrics, Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01278303
• Other Study ID Numbers: G060057a; RFD003898A
• First Posted: Jan 17, 2011
• Last Update Posted: Mar 14, 2016
• Last Verified: Feb 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Richard E. Ringel, Associate Professor of Pediatrics, Johns Hopkins University: Coarctation; Aorta
• Additional relevant MeSH terms: Aortic Coarctation

Study Results

Participant Flow

Arm/Group Title	Treatment of Aortic Wall Injury
Arm/Group Description	Repair of aortic wall injury with covered CP Stents Treatment of Aortic Wall Injury: A Cheatham covered platinum stent will be implanted in the Descending aorta to repair coarctation of the aorta in qualified patients.
Period Title: Overall Study
STARTED	82
COMPLETED	82
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment of Aortic Wall Injury
Arm/Group Description	Repair of aortic wall injury with covered CP Stents Treatment of Aortic Wall Injury: A Cheatham covered platinum stent will be implanted in the Descending aorta to repair coarctation of the aorta in qualified patients.
Overall Participants	82
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	18
Age (Count of Participants)
<=18 years	41 50%
Between 18 and 65 years	38 46.3%
>=65 years	3 3.7%
Sex: Female, Male (Count of Participants)
Female	30 36.6%
Male	52 63.4%
Region of Enrollment (participants) [Number]
United States	82 100%

Outcome Measures

1. Primary Outcome

Title	Study Participants With Grade 4 or 5 in Degree of Aortic Wall Injury (AWI) and/or Aortic Arch Obstruction Without Clinical Worsening
Description	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
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Participants available for analysis at one year

Arm/Group Title	Treatment of Aortic Wall Injury
Arm/Group Description	Repair of aortic wall injury with covered CP Stents Treatment of Aortic Wall Injury: A Cheatham covered platinum stent will be implanted in the Descending aorta to repair coarctation of the aorta in qualified patients.
Measure Participants	69
Number [participants]	55 67.1%

2. Secondary Outcome

Title	Secondary Efficacy Outcomes - 1 Year
Description	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
Time Frame	1 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment of Aortic Wall Injury
Arm/Group Description	Repair of aortic wall injury with covered CP Stents Treatment of Aortic Wall Injury: A Cheatham covered platinum stent will be implanted in the Descending aorta to repair coarctation of the aorta in qualified patients.
Measure Participants	82
(A) arm-leg SBP difference <15 mmHg	54 65.9%
(B) Good clinical status at 1 yr w/o worsening	55 67.1%

3. Secondary Outcome

Title	Secondary Safety Outcomes - Adverse Events
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment of Aortic Wall Injury
Arm/Group Description	Repair of aortic wall injury with covered CP Stents Treatment of Aortic Wall Injury: A Cheatham covered platinum stent will be implanted in the Descending aorta to repair coarctation of the aorta in qualified patients.
Measure Participants	82
Serious Adverse Events	1.2 1.5%
Somewhat Serious Adverse Events	11 13.4%

Adverse Events

Time Frame	1 year
Arm/Group Title	Treatment of Aortic Wall Injury
Arm/Group Description	Repair of aortic wall injury with covered CP Stents Treatment of Aortic Wall Injury: A Cheatham covered platinum stent will be implanted in the Descending aorta to repair coarctation of the aorta in qualified patients.
All Cause Mortality
	Treatment of Aortic Wall Injury
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment of Aortic Wall Injury
	Affected / at Risk (%)	# Events
Total	1/82 (1.2%)
Cardiac disorders
Aortic Wall Injury	1/82 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Treatment of Aortic Wall Injury
	Affected / at Risk (%)	# Events
Total	38/82 (46.3%)
Blood and lymphatic system disorders
Bruising or Hemorrhage	9/82 (11%)	9
Cardiac disorders
Arterial Wall Injury	2/82 (2.4%)	2
Aortic Wall Injury	4/82 (4.9%)	4
Device Specific	8/82 (9.8%)	8
Non-Classified	2/82 (2.4%)	2
Arrhythmia	2/82 (2.4%)	2
General disorders
Pain or Discomfort	8/82 (9.8%)	8
Infections and infestations
Infection	1/82 (1.2%)	1
Nervous system disorders
Neurologic Injury	2/82 (2.4%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.