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

A First-In-Human Trial of a New Novel DES (MiStent System) With Sirolimus and a Bioabsorbable Polymer for the Treatment of Patients With De Novo Lesions in the Native Coronary Arteries

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

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: 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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • St. Vincent's Hospital Melbourne
• Belgium
  • Aalst, Belgium
    • Onze-Lieve-Vrouwziekenhuis Aalst (OLV Hospital)
  • Genk, Belgium
    • Ziekenhuis Oost-Limburg
• New Zealand
  • Auckland, New Zealand, 1032
    • Auckland City Hospital
  • Aukland, New Zealand, 1032
    • Mercy Angiography Unit - Mercy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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).	Device: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Angiographic In-Stent Late Lumen Loss	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.	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Major Adverse Cardiac Events (MACE)	Major Adverse Cardiac Events (MACE) defined as death, myocardial infarction (Q-wave and non-Q-wave) and target vessel revascularization (TVR)	240 days
Device Success	Achievement of a final in-stent residual diameter stenosis of <50% (by QCA), using the assigned device only	8 hours
Lesion Success	Achievement of a final in-stent residual diameter stenosis of <50% (by QCA) using any percutaneous method	8 hours
Procedural Success	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	8 hours
Total Mortality	Total mortality (cardiac and non-cardiac)	240 days
Total Myocardial Infarction (MI)	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.; 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.	240 days
Clinically-driven Target Lesion Revascularization (TLR) Rates	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: A positive history of recurrent angina pectoris, presumably related to the target vessel;; Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel;; Abnormal results of any invasive functional diagnostic test (e.g., Doppler flow velocity reserve, fractional flow reserve);; A target lesion revascularization (TLR) with a diameter stenosis ≥ 70% even in the absence of the above-mentioned ischemic signs or symptoms.	240 days
Clinically-driven Target Vessel Revascularization (TVR) Rates	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: A positive history of recurrent angina pectoris, presumably related to the target vessel;; Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel;; Abnormal results of any invasive functional diagnostic test (e.g., Doppler flow velocity reserve, fractional flow reserve);; A target vessel revascularization (TVR) with a diameter stenosis ≥ 70% even in the absence of the above-mentioned ischemic signs or symptoms.	240 days
Target Vessel Failure (TVF)	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	240 days
Target Lesion Failure (TLF)	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	240 days
Stent Thrombosis	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	240 days
Angiographic Evaluation: In-stent Binary Restenosis	Binary Restenosis is defined as ≥50% luminal narrowing at follow-up angiography.	4 months, 6 months, 8 months
Angiographic Evaluation: In-stent Binary Restenosis	Binary Restenosis is defined as ≥50% luminal narrowing at follow-up angiography.	18 months
Intravascular Ultrasound (IVUS) Evaluation: % Neointimal Volume Obstruction	% neointimal volume obstruction is defined as the neointimal volume divided by stent volume.	8 months
IVUS Evaluation: % Neointimal Volume Obstruction	% neointimal volume obstruction is defined as the neointimal volume divided by stent volume.	18 months
Optical Coherence Tomography (OCT) Evaluation: % Stent Strut Uncovered	% stent strut uncovered is defined as the ratio of uncovered struts to total struts in all cross-sections.	8 months
OCT Evaluation: % Stent Strut Uncovered	% stent strut uncovered is defined as the ratio of uncovered struts to total struts in all cross-sections.	18 M

Collaborators and Investigators

• Sponsor: Micell Technologies
• Investigators: Principal Investigator: John Ormiston, MD, Mercy Angiography Unit

Publications and helpful links

General Publications

• Ormiston J, Webster M, Stewart J, Vrolix M, Whitbourn R, Donohoe D, Knape C, Lansky A, Attizzani GF, Fitzgerald P, Kandzari DE, Wijns W. First-in-human evaluation of a bioabsorbable polymer-coated sirolimus-eluting stent: imaging and clinical results of the DESSOLVE I Trial (DES with sirolimus and a bioabsorbable polymer for the treatment of patients with de novo lesion in the native coronary arteries). JACC Cardiovasc Interv. 2013 Oct;6(10):1026-34. doi: 10.1016/j.jcin.2013.05.013. Epub 2013 Sep 18.
• Attizzani GF, Bezerra HG, Ormiston J, Wang W, Donohoe D, Wijns W, Costa MA. Serial assessment by optical coherence tomography of early and late vascular responses after implantation of an absorbable-coating Sirolimus-Eluting stent (from the first-in-human DESSOLVE I trial). Am J Cardiol. 2013 Nov 15;112(10):1557-64. doi: 10.1016/j.amjcard.2013.07.013. Epub 2013 Aug 29.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ACTUAL): September 1, 2012
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: November 18, 2010
• First Submitted That Met QC Criteria: November 23, 2010
• First Posted (ESTIMATE): November 24, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): December 19, 2016
• Last Update Submitted That Met QC Criteria: December 15, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Sirolimus; Drug-eluting Stent
• 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-FIH-2010-01

Plan for Individual participant data (IPD)

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