To evaluate the safety and effectiveness of Orsiro for the treatment of subjects with up to 2 de novo atherosclerotic coronary artery lesions.
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint for the main randomized controlled trial (RCT) is the
12-month target vessel failure (TVF) rate, defined as any clinically-driven
revascularization of the target vessel (TVR), target vessel Q-wave or non-Q
wave myocardial infarction (MI), emergent CABG, or cardiac death -. The primary
endpoint will be evaluated for all subjects who are randomized to one of the
study stents (Orsiro or Xience Prime/Xpedition). The RCT will be considered
complete with regard to the primary endpoint after all subjects have completed
the 12-month follow-up.
Secondary outcome
The below listed endpoints will be evaluated for events that occurred prior to
discharge, 1-, 6- and 12-months and 2-, 3-, 4- and 5-years post procedure.
Subjects who are randomized but who do not receive a study stent (Orsiro or
XIENCE) will be followed through 12 months only. Starting with the 2-year
follow-up, follow-up will be limited to the implanted population.
1. Rate of clinically-driven target lesion revascularization (TLR)
2. Rate of clinically-driven TVR
3. Rate of target lesion failure (TLF), defined as composite of cardiac death,
target vessel Q-wave or non-Q wave MI, emergent CABG, any clinically-driven
TLR
4. Rate of TVF
5. Rate of Q-wave and non-Q-wave MI
6. Rate of cardiac death
7. Rate of non-cardiac death
8. Rate of all death
9. Rate of cardiac death or MI
10. Rate of all death or MI
11. Rate of all death, MI and TVR
12. Rate of stent thrombosis (definite or probable by ARC definitions)
13. Rate of cerebrovascular disease
Periprocedural endpoints measured in the RCT and HuPK sub-study are listed
below.
1. Technical success rate
2. Clinical procedural success rate
Background summary
Since the first Percutaneous Transluminal Coronary Angioplasty (PTCA), this
procedure has become a widely accepted treatment modality for Coronary Artery
Disease (CAD). For the majority of CAD, treatment with PTCA provides high
initial procedural success, symptomatic relief, improvement in functional
capacity, and survival rates quite similar to those of Coronary Artery Bypass
Grafting (CABG). However, all percutaneous techniques, regardless of the mode
of intervention, have rather high rates of repeat interventions at long-term
follow up. The first type of stent used in Percutaneous Coronary Intervention
(PCI), were Bare Metal Stents (BMS), designed to address the limitations of
PTCA. BMS reduced the angiographic and clinical restenosis rates in de novo
lesions compared to PTCA alone and decreased the need for CABG. BMS
substantially reduced the incidence of abrupt artery closure, but restenosis
occurred in about 20%-40% of all cases, necessitating repeat procedures. The
invention of Drug Eluting Stents (DES) significantly improved on the principle
of BMS by adding an antiproliferative drug, which is either directly
immobilized on the stent surface or released from a polymer matrix to inhibit
neointimal hyperplasia. This allows for controlled release of the drug at the
site of injury. The polymer drug carriers currently used on DES are either
biodegradable or non-biodegradable. Non-biodegradable polymers reside on the
surface of the stent indefinitely. In contrast biodegradable polymers dissolve
after a certain period of time, leaving only the BMS platform in the vessel
wall. The introduction of DES greatly reduced the incidence of restenosis and
resulted in a better safety profile as compared to BMS with systemic drug
administration. These advantages and a lower cost compared to surgical
interventions have made DES an attractive option to treat coronary artery
disease.
This study will collect data prospectively on subjects that are randomly
assigned to be implanted with either the Biotronik Orsiro or the Abbott Xience
Prime* / Xience Xpedition* stent. The Xience Prime and Xience Xpedition stents
differ in the delivery system. The stent itself is exactly the same. All
investigational devices have received the CE mark and are available on the
market. By comparing two different products of the latest generation, we expect
to gain more knowledge on the safety and efficacy of the Orsiro stent. The
built evidence through this study may also provide useful insights for the
continuous development of drug eluting stents.
Study objective
To evaluate the safety and effectiveness of Orsiro for the treatment of
subjects with up to 2 de novo atherosclerotic coronary artery lesions.
Study design
BIOFLOW-IV is a prospective, international multicenter, randomised controlled
trial to assess Orsiro for the treatment of subjects with up to 2 de novo
atherosclerotic coronary artery lesions. All subjects will be randomised 2:1
to receive the BIOTRONIK Orsiro SES or the Abbott Xience Prime* / Xience
Xpedition* EES. The randomisation will be stratified for diabetes.
Approximately 555 subjects at up to ca. 50 sites in Japan and Europe are
proposed to demonstrate the safety and effectiveness of Orsiro.
A randomized controlled trial (RCT) at up to ca.50 sites in Japan and Europe
aims to enter 555 subjects. All subjects will be randomised 2:1 to receive the
Orsiro or the Xience Prime* / Xience Xpedition*.
During study enrolment phase, all patients will be screened according to the
protocol inclusion and exclusion criteria. All patients consented will undergo
angiographic assessment during the index procedure a spart of standard clinical
care.
Clinical telephone follow up visits will take place at 1, 6 months and annually
for 5 years post procedure. At 12 months an outpatient visit at the site is
required to assess the clinical status.
Protocol mandated angiographic follow-up is not required; however, patients
requiring re-intervention for the target vessel(s) during the 5 year follow up
period will undergo angiographic assessment at the time of re-intervention as
standard of care. Angiographic data and images collected during the index
procedure and during re-intervention (if applicable) must be forwarded to the
Angiographic Core Laboratory for analysis.
This clinical trial is designed to be performed in accordance with the
Declaration of Helsinki 2008, ISO 14155 (E), the Pharmaceutical Affairs Laws
and regulations related to clinical trials in Japan (Japanese Good Clinical
Practice), and Local and National regulations.
Study burden and risks
The nature and extent of the burden, risks and benefits associated with
participation are described for baseline and follow up.
Baseline
All baseline examinations prior to randomization are according to standard
clinical care.
Implantation of the devices will not bring additional risk to the subjects,
then otherwise experience in standard clinical care.
None of the study patients will have any planned additional invasive or
non-invasive examinations/procedures during the PTCA procedure.
All diagnostic examinations post-procedure are according to standard clinical
care. The study does not include any additional study specific invasive or
non-invasive examination(s).
In summary we conclude that the anticipated rate of events for study patients
and regular patients are equal.
A complete description of associated possible adverse events and correct usage
of the Orsiro and the Xience Prime/Xpedition stents are described in each
device instructions for use.
Follow up
During follow up all patients will be requested to return for an outpatient
visit at 12 months, to assess their clinical status. This will be done
according to standard clinical practice.
A standard ECG will be collected during this visit. No blood samples will be
drawn.
In summary, there are no anticipated increased risks associated with the follow
up visit at 12 months.
All other follow up visits will be done by telephone interview and will not
bring any additional risk to the patient(s).
Benefits
In this clinical investigation all subjects will have a more frequent medical
follow up then otherwise provided in standard clinical care. This may be
beneficial for the long term clinical outcome of the patient.
The collected data will provide more knowledge to the long term safety and
efficacy of the Orsiro SES and the Xience Prime*/Xience Expedition* EES.
Conclusion
Except for the randomization at baseline and the mandatory physical examination
at 12 month follow up, all study patients will receive equal treatment as
non-study patients with the same diagnose.
The stents used in this study are available and used in standard clinical care.
The study may, but is not certain to bring a direct benefit to the individual
patient by the more intense medical follow up.
The knowledge gained through the study might help to improve the therapy for
future patients.
In summary we conclude that the study patients will experience no plausible
additional risk by participating in this clinical study.
Ackerstrasse 6
Buelach 8180
CH
Ackerstrasse 6
Buelach 8180
CH
Listed location countries
Age
Inclusion criteria
Clinical Inclusion Criteria
1. Subject must provide written informed consent
2. Subject is * 18 years and * 80 years old
3. For subject less than 20 years of age enrolled at a Japanese site, the patient and the patient*s legal representative must provide written informed consent before any study-specific tests or procedures are performed
4. Subject, target vessel(s) and lesion(s) are eligible for percutaneous coronary intervention (PCI)
5. Subject is an acceptable candidate for coronary artery bypass grafting (CABG)
6. Subject has clinical evidence of ischemic heart disease and/or a positive functional study, stable or unstable angina pectoris or documented silent ischemia, attributable to the target lesions
7. Subject is eligible for dual anti-platelet therapy (DAPT) treatment with acetylsalicylic acid (ASA) plus either, Clopidogrel, Prasugrel, Ticlopidine, or Ticagrelor. For subjects enrolled at a Japanese site, DAPT with ASA plus either Clopidogrel or Ticlopidine;Angiographic Inclusion Criteria
1. The target reference vessel diameter (RVD) is * 2.50 mm and * 3.75 mm assessed either visually or by online Quantitative Coronary Angiography.
2. Target lesion length is * 26 mm (assessed either visual estimate or by online Quantitative Coronary Angiography) and can be covered by one study stent
3. Single de novo lesion with * 50% and < 100% stenosis in up to 2 coronary arteries
4. Target vessel(s) Thrombolysis in Myocardial Infarction (TIMI) flow * 2
Exclusion criteria
Clinical Exclusion Criteria;1. Subject has evidence of myocardial infarction within 72 hours prior to the index procedure
2. Subject with a *2 fold CK level or in absence of CK *3 fold CKMB level above the upper range limit within 24 hours prior to the procedure
3. Documented recent left ventricular ejection fraction (LVEF) * 30%
4. Subject is receiving oral or intravenous immunosuppressive therapy (i.e., inhaled steroids are not excluded) or has known life-limiting immunosuppressive or autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematosus, but not including diabetes mellitus)
5. Subject has impaired renal function (i.e., serum creatinine > 2.5 mg/dl or 221 mmol/l, determined within 72 hours prior to intervention)
6. Target vessel(s) or side branch has been treated with any type of PCI (e.g., balloon angioplasty, stent, cutting balloon, atherectomy) within 12 months prior to the index procedure
7. The target lesion requires treatment with a device other than the pre-dilatation balloon prior to stent placement (including but not limited to, directional coronary atherectomy, excimer laser, rotational atherectomy, cutting balloon etc.)
8. Planned intervention of non-target vessel(s) within 30 days after the index procedure
9. Planned intervention of target vessel(s) after the index procedure
10. Subject has a known allergy to contrast medium (that cannot be adequately premedicated), acetylsalicylic acid (ASA), heparin, PLLA, sirolimus, everolimus, cobalt chromium, nickel, or silicon carbide.
11. Subject is currently participating in another (medical device or drug) clinical study that has not reached the primary endpoint
12. Subject is pregnant and/or breast-feeding female or female who intends to become pregnant during the time of the study
13. Subject has serious medical illness (e.g., cancer, congestive heart failure) that may reduce life expectancy to less than 12 months
14. Planned surgery or dental surgical procedure within 6 months after index procedure
15. Three-vessel coronary artery disease at time of procedure
16. In the investigators opinion subject will not be able to comply with the follow up requirements;Angiographic Exclusion Criteria;1. Target lesion is located in the left main stem
2. Target lesion is located in or supplied by an arterial or venous bypass graft
3. Target lesion involves a side branch > 2.0 mm in diameter by visual estimate or by online quantitative coronary angiography
4. Ostial target lesion (within 5.0mm of vessel origin)
5. Thrombus, or possible thrombus, present in the target vessel
6. Heavily calcified lesion
7. Proximal or distal to the target lesion located stenosis that might require future revascularization or impede run off;Note: Multiple focal stenosis will be considered as a single lesion if they can be completely covered with 1 stent
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT01939249 |
| CCMO | NL47384.100.14 |