First-In-Human Trial of the MiStent Drug-Eluting Stent (DES) in Coronary Artery Disease

Phase 2

Completed

• Conditions: Coronary Artery Disease
• Interventions: Device: MiStent SES

• Registration Number: NCT01247428
• Lead Sponsor: Micell Technologies

Brief Summary

The DESSOLVE I clinical trial is to assess the safety and performance of the sirolimus-eluting MiStent SES.

Detailed Description

The DESSOLVE I clinical trial is to assess the safety and performance of the sirolimus-eluting MiStent for the treatment for improving coronary luminal diameter in patients with symptomatic ischemic heart disease due to discrete de novo lesions \< 20 mm in length in the native coronary arteries with reference vessel diameters between 2.5 mm and 3.5 mm.

Study Timeline

• Study Start: 2010-11
• Study First Submitted: 2010-11-18
• Study First Submitted QC: 2010-11-23
• Study First Posted: 2010-11-24
• Primary Completion: 2012-09
• Results First Submitted: 2013-12-19
• Results First Submitted QC: 2014-06-10
• Results First Posted: 2014-06-12
• Study Completion: 2016-03
• Status Verified: 2016-12
• Last Update Submitted: 2016-12-15
• Last Update Posted: 2016-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Male/female patients 18-85 years;
2. Stable or unstable angina pectoris, ischemia, or silent ischemia;
3. Planned single, de novo, types A, B1 and B2 coronary lesions;
4. Target lesion located in a native coronary artery;
5. Target lesion vessel diameter 2.5 to 3.5 mm amenable to treatment with a maximum 23 mm long stent;
6. Target lesion >50% diameter stenosis;
7. Patients eligible for percutaneous coronary intervention (PCI);
8. Acceptable candidate for myocardial revascularization surgery;
9. A patient may have one additional critical non-target lesion.
10. The patient will provide written informed consent.

Exclusion Criteria

1. Female of childbearing potential not on some form of birth control with a confirmed negative pregnancy test at baseline;

2. Recent Q-wave myocardial infarction occurred <72 hours prior to the index procedure. Recent myocardial infarction with elevated levels of cardiac markers;

3. Left ventricular ejection fraction <30%;

4. Patients in cardiogenic shock;

5. Cerebrovascular accident or transient ischemic attack within 6 months;

6. Active GI bleed within three months;

7. Any prior true anaphylactic reaction to contrast agents;

8. Patient receiving/scheduled to receive chemotherapy within 30-days before or after the index procedure;

9. Patient is receiving immunosuppressive therapy or has known life-limiting immunosuppressive/autoimmune disease;

10. Renal dysfunction (creatinine > 2.0 mg/dL or 177 µmol/L);

11. Platelet count <100,000 cells/mm³ or >700,000 cells/mm³;

12. White blood cell count <3,000 cells/mm3;

13. Hepatic disease;

14. Heart transplant recipient;

15. Known contraindication to dual antiplatelet therapy;

16. Known hypersensitivity to sirolimus, cobalt-chromium, or to medications such as aspirin, heparin, and all three of the following: clopidogrel bisulfate (Plavix), ticlopidine (Ticlid), and Prasugrel (Effient);

17. Life expectancy <12 months;

18. Any major medical condition that may interfere with the optimal participation of the patient in this study;

19. Patient is currently participating/planning to participate in an investigational drug or another device study prior to completing 12-months follow-up;

20. Target vessel(s) has been treated within 10 mm proximal or distal to target lesion with any type of PCI within a year prior to index procedure;

21. Planned or actual target vessel(s) treatment with an unapproved device, directional or rotational coronary atherectomy, laser, cutting balloon, or transluminal extraction catheter prior to stent placement;

22. Previous coronary intravascular brachytherapy;

23. Planned coronary angioplasty or coronary artery bypass grafting (CABG)in the first 9 months after the index procedure;

24. Prior PCI of a non-target vessel must be at least 30 days prior to study enrollment;

25. The intent to direct stent the target lesion;

26. Angiographic Exclusion Criteria: Assessed prior to stent placement;

    • In-stent restenotic target lesion;
    • More than one lesion requiring treatment in the target vessel;
    • Target vessel diameter <2.5 mm or >3.5 mm;
    • Target lesion not amenable to treatment with a 23 mm long stent;
    • Unprotected coronary artery branch lesion (≥50% DS);
    • Target lesion located in a surgical bypass graft;
    • Total vessel occlusion;
    • Target lesion with ostial location;
    • Target lesion located in a lateral branch bifurcation >2.5mm or requiring lateral branch stenting;
    • Calcified target lesion that anticipates unsuccessful/impracticable predilation;
    • Target vessel excessive tortuosity or proximal angulation (>90 degrees);
    • Thrombus present in target vessel;
    • More than one non-target critical lesion;

Non-target lesion to be treated during the index procedure meets any of the following criteria:

• Within the target vessel;
• Within a bypass graft;
• Left main location;
• Chronic total occlusion;
• Involves a complex bifurcation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MiStent SES	MiStent SES	The MiStent SES is a device/drug combination comprised of two components; a stent and a drug product (sirolimus within an absorbable polymer coating).

Primary Outcome Measures

Name	Time	Method
Angiographic In-Stent Late Lumen Loss	8 months	In-stent late lumen loss as measured by the angiographic core laboratory as the difference between the post-procedure minimal lumen diameters (MLD) in the treated segment (stented region) minus the MLD in the same region at follow-up.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Major Adverse Cardiac Events (MACE)	240 days	Major Adverse Cardiac Events (MACE) defined as death, myocardial infarction (Q-wave and non-Q-wave) and target vessel revascularization (TVR)
Procedural Success	8 hours	Achievement of a final in-stent residual diameter stenosis of \<50% (by QCA) using the assigned device (including any adjunctive devices) without cardiac death, Myocardial infarction (MI) or repeat revascularization of the target lesion pre-hospital discharge
Clinically-driven Target Lesion Revascularization (TLR) Rates	240 days	A revascularization is considered clinically driven if angiography at follow-up shows a percent diameter stenosis ≥ 50% (Angiographic Core Laboratory QCA assessment) and if one of the following occurs: 1. A positive history of recurrent angina pectoris, presumably related to the target vessel; 2. Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel; 3. Abnormal results of any invasive functional diagnostic test (e.g., Doppler flow velocity reserve, fractional flow reserve); 4. A target lesion revascularization (TLR) with a diameter stenosis ≥ 70% even in the absence of the above-mentioned ischemic signs or symptoms.
Target Vessel Failure (TVF)	240 days	Target vessel failure (TVF) is defined as the composite endpoint of: * cardiac death,; * target-vessel myocardial infarction (Q wave or non-Q wave), and; * clinically indicated target vessel revascularization
Device Success	8 hours	Achievement of a final in-stent residual diameter stenosis of \<50% (by QCA), using the assigned device only
Total Myocardial Infarction (MI)	240 days	1. Q-wave MI (QWMI): requires one of the following criteria: the development of new abnormal Q waves in ≥2 contiguous ECG leads not present on the patient's baseline (i.e., before intervention) in association with a \>2x upper limit normal elevation of creatine kinase (CK) levels. In the absence of ECG data, the clinical events committee may adjudicate a Q-wave MI based on the clinical scenario and appropriate cardiac enzyme data; chest pain or other acute symptoms consistent with myocardial ischemia and new pathological Q waves in ≥2 contiguous ECG leads in the absence of timely cardiac enzyme data.; 2. Non-Q-wave MI (NQWMI): the elevation of CK levels (≥2 times ULN) with elevated CK-MB enzyme levels in the absence of new pathologic Q waves.
Clinically-driven Target Vessel Revascularization (TVR) Rates	240 days	A revascularization is considered clinically driven if angiography at follow-up shows a percent diameter stenosis ≥ 50% (Angiographic Core Laboratory QCA assessment) and if one of the following occurs: 1. A positive history of recurrent angina pectoris, presumably related to the target vessel; 2. Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel; 3. Abnormal results of any invasive functional diagnostic test (e.g., Doppler flow velocity reserve, fractional flow reserve); 4. A target vessel revascularization (TVR) with a diameter stenosis ≥ 70% even in the absence of the above-mentioned ischemic signs or symptoms.
Stent Thrombosis	240 days	The presence of an intracoronary thrombus that originates in the stent or in the segments 5 mm proximal or distal to the stent post-procedure
Angiographic Evaluation: In-stent Binary Restenosis	18 months	Binary Restenosis is defined as ≥50% luminal narrowing at follow-up angiography.
Optical Coherence Tomography (OCT) Evaluation: % Stent Strut Uncovered	8 months	% stent strut uncovered is defined as the ratio of uncovered struts to total struts in all cross-sections.
Lesion Success	8 hours	Achievement of a final in-stent residual diameter stenosis of \<50% (by QCA) using any percutaneous method
Total Mortality	240 days	Total mortality (cardiac and non-cardiac)
Target Lesion Failure (TLF)	240 days	Target lesion failure (TLF) is defined as the composite endpoint of: * cardiac death,; * target-lesion myocardial infarction (Q wave or non-Q wave), and; * clinically indicated target lesion revascularization
Intravascular Ultrasound (IVUS) Evaluation: % Neointimal Volume Obstruction	8 months	% neointimal volume obstruction is defined as the neointimal volume divided by stent volume.
IVUS Evaluation: % Neointimal Volume Obstruction	18 months	% neointimal volume obstruction is defined as the neointimal volume divided by stent volume.
OCT Evaluation: % Stent Strut Uncovered	18 M	% stent strut uncovered is defined as the ratio of uncovered struts to total struts in all cross-sections.

Trial Locations

Locations (5)

Auckland City Hospital; 🇳🇿 Auckland, New Zealand

Mercy Angiography Unit - Mercy Hospital; 🇳🇿 Aukland, New Zealand

Ziekenhuis Oost-Limburg; 🇧🇪 Genk, Belgium

St. Vincent's Hospital Melbourne; 🇦🇺 Melbourne, Australia

Onze-Lieve-Vrouwziekenhuis Aalst (OLV Hospital); 🇧🇪 Aalst, Belgium