Trial to Demonstrate the Safety and Effectiveness of the MiStent II for the Revascularization of Coronary Arteries. (CRYSTAL)

CRYSTAL Study: A Multi-Center, Randomized, Controlled Trial to Demonstrate the Safety and Effectiveness of the MiStent II for the Revascularization of Coronary Arteries.

To compare MiStent to either the Xience or Promus stents.with the primary objective being to assess the safety and efficacy of the MiStent in a patient population requiring revascularization of de novo obstructive lesions of coronary arteries in patients with stable and unstable coronary artery disease (CAD) including non ST-Elevation Myocardial Infarction (NSTEMI)

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: MiStent II coronary artery stent; Device: Xience or Promus coronary artery stents

Detailed Description

The CRYSTAL study is a prospective, multi-center, randomized (1:1), single-blinded and controlled, investigational device exemption trial to test the non-inferiority of MiStent to commercially available "everolimus" drug eluting stents (Xience and Promus stents).

Patients with coronary artery disease (CAD) that qualify for percutaneous coronary intervention (PCI) with stenting will be screened per the protocol inclusion and exclusion criteria.

• Study Type: Interventional
• Enrollment (Anticipated): 1300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jeffrey Mifek; Phone Number: 919-313-2102; Email: jmifek@micell.com
• Study Contact Backup: Name: Christopher DiMatteo; Phone Number: 480-765-8584; Email: cdimatteo@namsa.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject must be ≥ 18 years of age
2. Subject (or legal guardian) understands the trial requirements and the treatment procedures and provides written informed consent before any trial-specific tests or procedures are performed
3. Subject is eligible for percutaneous coronary intervention (PCI)
4. Subject has symptomatic coronary artery disease with objective evidence of ischemia or silent ischemia
5. Subject is an acceptable candidate for coronary artery bypass grafting (CABG)

6. Subject is willing to comply with all protocol-required follow-up evaluation

   Angiographic Inclusion Criteria (visual estimate):

7. Target lesion(s) must be located in a native coronary artery with a visually estimated reference vessel diameter (RVD) ≥2.50 mm and ≤3.50 mm

8. Target lesion(s) must be able to be treated with a single stent and the target lesion length must be ≤27 mm (by visual estimate).

   NOTE: Only lesion lengths that have both the control and comparable investigational stent lengths available at the same time are eligible for enrollment.

9. Target lesion(s) must have visually estimated stenosis ≥50% and <100% with thrombolysis in Myocardial Infarction (TIMI) flow >1 and one of the following:

   1. Stenosis ≥70% or;
   2. Abnormal fractional flow reserve (FFR) defined as <0.80 or;
   3. Abnormal stress or imaging stress test or;
   4. Elevated biomarkers prior to the procedure
10. Coronary anatomy is likely to allow delivery of a study device to the target lesions(s)
11. The first lesion treated must be successfully predilated/pretreated

Exclusion Criteria:

1. Subject has clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute ST elevation MI (STEMI)
2. Subject has cardiogenic shock, hemodynamic instability requiring inotropic or mechanical circulatory support, intractable ventricular arrhythmias, or ongoing intractable angina
3. Subject has received an organ transplant or is on a waiting list for an organ transplant
4. Subject is receiving or scheduled to receive chemotherapy within 30 days before or after the index procedure
5. Planned PCI (including staged procedures) or CABG after the index procedure
6. Subject previously treated at any time with intravascular brachytherapy in the target vessel(s)
7. Subject has a known allergy to contrast (that cannot be adequately premedicated) and/or the trial stent system or protocol-required concomitant medications (e.g., Cobalt-chromium alloy, stainless steel, everolimus or structurally related compounds, polymer or individual components, all P2Y12 inhibitors, or aspirin)

8. Subject has one of the following (as assessed prior to the index procedure):

   1. Other serious medical illness (e.g., cancer, congestive heart failure) with estimated life expectancy of less than 24 months
   2. Current problems with substance abuse (e.g., alcohol, cocaine, heroin, etc.)
   3. Planned procedure that may cause non-compliance with the protocol or confound data interpretation
9. Subject is receiving chronic (≥72 hours) anticoagulation therapy (i.e., heparin, coumadin, or other anticoagulation therapy) for indications other than acute coronary syndrome
10. Subject has a platelet count <100,000 cells/mm3 or >700,000 cells/mm3
11. Subject has a white blood cell (WBC) count < 3,000 cells/mm3
12. Subject has documented or suspected liver disease, including laboratory evidence of hepatitis
13. Subject is on dialysis or has baseline glomerular filtration rate (GFR) of <30 ml/min
14. Subject has a history of bleeding diathesis, active peptic ulcer or gastrointestinal (GI) bleed, or coagulopathy or will refuse blood transfusions
15. Subject has had a history of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the past 6 months
16. Subject has severe symptomatic heart failure (i.e., Left Ventricular Ejection Fraction (LVEF) <30%))
17. Subject is participating in another investigational drug or device clinical trial that has not reached its primary endpoint
18. Subject intends to participate in another investigational drug or device clinical trial within 12 months after the index procedure
19. Subject with known intention to procreate within 12 months after the index procedure (women of child-bearing potential who are sexually active must agree to use a reliable method of contraception from the time of screening through 12 months after the index procedure)

20. Subject is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential)

    Angiographic Exclusion Criteria (visual estimate):

21. Planned treatment of a single lesion with more than 1 stent
22. Planned treatment of more than 3 lesions
23. Planned treatment of lesions in more than 2 major epicardial vessels
24. Planned treatment of more than 2 lesions in a single major epicardial vessel
25. Subject has 2 target lesions in the same vessel that are separated by less than 15 mm (by visual estimate)
26. Target lesion(s) is located in the left main or unprotected left
27. Target lesion(s) is located within 3 mm of the origin of the left anterior descending (LAD) coronary artery or left circumflex (LCx) coronary artery by visual estimate
28. Target lesion(s) is located within a saphenous vein graft or an arterial graft
29. Target lesion(s) will be accessed via a saphenous vein graft or arterial graft
30. Target lesion(s) with a TIMI flow 0 (total occlusion) or TIMI flow 1 prior to guide wire crossing
31. Target lesion(s) treated during the index procedure that involves a complex bifurcation (e.g., bifurcation lesion requiring treatment with more than 1 stent)
32. Target lesion(s) is restenotic from a previous stent implantation or study stent would overlap with a previous stent
33. Subject has been treated with any type of PCI (i.e., balloon angioplasty, stent, cutting balloon atherectomy) within 24 hours prior to the index procedure
34. Significant thrombus, present in the target vessel (by visual estimate)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MiStent II Coronary Artery Stent; Implantation of a coronary artery stent in an all-comers population, including patients with symptomatic coronary artery disease including patients with chronic stable angina, silent ischemia, and acute coronary syndromes, who qualify for percutaneous coronary interventions	Device: MiStent II coronary artery stent; Implantation of a coronary stent patient with stable and unstable coronary artery disease including non-ST-Elevated Myocardial Infarction
Active Comparator: Xience or Promus Coronary Artery Stents; Implantation of a coronary artery stent in an all-comers population, including patients with symptomatic coronary artery disease including patients with chronic stable angina, silent ischemia, and acute coronary syndromes, who qualify for percutaneous coronary interventions	Device: Xience or Promus coronary artery stents; Implantation of a coronary stent patient with stable and unstable coronary artery disease including non-ST-Elevated Myocardial Infarction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target Lesion Failure (TLF)	Any occurrence of Target Lesion Failure (TLF) TLF is defined as: Cardiac death, or Target vessel myocardial infarction (TV-MI, Q-wave and non Q-wave), or Ischemia driven target lesion revascularization.	through 12-month visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device success	Successful delivery and deployment of the study stent to the target vessel, without balloon rupture or stent embolization with post procedure diameter stenosis of < 30% (by visual estimation) in the Target Lesion.	Index Procedure
Technical success	Achieving a final diameter stenosis of <30% (by visual estimation) in the target lesion using any combination of stents or devices allowed per protocol.	Index Procedure
Procedural success	Post-procedure diameter stenosis <30% (by visual estimation) in all target lesions and the absence of in-hospital MI, TVR, or cardiac death.	Index Procedure
Composite Endpoint POCE	POCE defined as all-cause death, any MI, or any revascularization	prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up
Composite Endpoint MACE	MACE defined as all-cause death, any MI, or any TVR	prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up
Composite Endpoint TVF	TVF defined as cardiac death, TV MI, or clinically indicated TVR	prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up
Composite Endpoint TLF	TLF defined as cardiac death, TV MI or Ischemia driven TLR	prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up
Mortality	Mortality including All death, Cardiac death, and Non-cardiac death (vascular and non-cardiovascular)	prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up
Myocardial Infarction	Myocardial Infarction including All MI, TV-MI, and Non-TV-MI	prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up
Revascularization	Revascularization including Target Lesion revascularization (TLR) (any, clinically- indicated TLR, non-clinically indicated TLR), Target Vessel revascularization (TVR) (any, clinically- indicated TVR, non-clinically indicated TVR), Non-TV revascularization, and Any revascularization	prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up
Stent thrombosis rates	Stent thrombosis rates according to ARC classification: ST - Early (Acute, Sub-acute), Late, Very Late; ST - Definite, Probable, Possible	prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up
Serious Adverse Events (SAEs)	All SAEs through 12 months' post-index procedure; All device related SAEs from 12 months through 5 years' post-index procedure	prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up

Collaborators and Investigators

• Sponsor: Micell Technologies
• Collaborators: Yale Cardiovascular Research Group; North American Science Associates Inc.; Baim Institute for Clinical Research
• Investigators: Principal Investigator: Dean Kereiakes, MD, The Christ Hospital; Study Chair: Laura Mauri, MD, MSc, Brigham and Women's Hospial

Study record dates

Study Major Dates

• Study Start (Anticipated): December 31, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2027

Study Registration Dates

• First Submitted: January 23, 2018
• First Submitted That Met QC Criteria: January 30, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): September 4, 2020
• Last Update Submitted That Met QC Criteria: September 3, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Vascular Diseases; Cardiovascular Diseases; Coronary Artery Disease; MiStent; Heart Disease; Arteriosclerosis; Myocardial Ischemia; Coronary Disease; Arterial Occlusive Diseases
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: MIS-US-2017-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes