1) Safety: Non inferiority of the BioFreedom* to the Gazelle* Bare Metal Stent in patients treated with one month DAPT only followed by aspirin alone. The non-inferiority will be assessed by the composite endpoint of CD, MI and ST at 1 year.2)…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoints:
Safety:
1. The composite of cardiac death, myocardial infarction and definite/probable
stent thrombosis at one year.
Efficacy:
2. The incidence of clinically driven target lesion revascularization at one
year.
Secondary outcome
Secondary Endpoints: [At all protocol defined follow-up time points (1, 2 and 4
months and 1 and 2 years) unless otherwise indicated]
1. Primary endpoints at 2 years
2. Bleeding per BARC criteria
a. BARC 3 to 5
b. All BARC
c. By vascular access site (Femoral/Radial)
3. All individual components of the primary endpoint (see below)
a. Cardiac Death
b. Myocardial infarction (according to the Third universal definition Q
wave, Non-Q wave and all Myocardial Infarction
c. Stent Thrombosis, per ARC definition of definite and probable
4. Stent Thrombosis per ARC definition
a. Definite, Probable and Possible
b. Definite
5. Urgent TLR
6. Clinically driven TLR at times points other than the primary endpoint
7. Clinically driven target vessel revascularization
8. All cause mortality
9. Primary endpoints at 1 year, in patients with at least 1 lesion treated with
a trial stent of 3mm or less in nominal diameter
10. Cost effectiveness (1 year; in predefined European countries)
11. Quality of Life (1 year; in predefined European countries)
Background summary
Atherosclerosis and coronary artery thrombosis are a major cause of premature
death worldwide, and are source of loss of disability-adjusted life years.
Treatment goals for patients with CAD are improvement in survival and a
reduction in the risk of heart attack and symptoms of coronary disease. Balloon
angioplasty with stent implantation of narrowed coronary lesions that cause a
lack of blood supply to the heart can improve a patient's functional status and
outcome.
Stents have been continuously improved in order to ensure better outcomes for
patients. Currently, most stents are covered with a drug to reduce the risk of
re-narrowing. One of the drugs which are widely used is Biolimus A9*, a strong
anti-inflammatory agent, which suppresses the growth of certain cells in the
arteries.
In order to prevent blood from clotting within the stent, the blood needs to be
modified slightly. This is accomplished through the simultaneous treatment with
two antiplatelet drugs (Aspirin plus either Clopidogrel or Prasugrel or
Ticagrelor). The type of stents covered with drugs called *drug-eluting stents*
require a longer (6 to 12 months) treatment with double antiplatelet drugs than
the stents not covered with a drug, the so-called *bare-metal stents (BMS)*.
BMS require only one month of the double antiplatelet treatment because the
time necessary for the artery to heal is shorter with bare metal stents than
with drug-eluting stents.
While the prolonged double treatment does not cause any harm in most patients,
there are some patients in whom the advantage of diminishing the risk of
re-narrowing is offset by the increased bleeding risk due to the longer time
that they need to take double antiplatelet treatment. A new generation of
stents, called *drug coated stents* has been developed. . While in *drug-
eluting stents* the drug is embedded in a synthetic polymer, which is attached
to the metal backbone of the stent, in *drug coated stents* there is not any
polymer used, but the stent is directly coated with the drug. This new stent
has the potential to combine the benefit of being coated with a drug that
prevents re-narrowing with the advantage of not requiring the prolonged dual
anti-platelet treatment, because the healing process is possibly faster than
with a drug eluting stent.
The stents used in this study are either the latest generation of stents, the
drug coated stents, or uncovered stents, the bare-metal stents (BMS).
The Leaders free study will examine the risk/benefit of prolonged dual blood
thinning medication in angioplasty and stented patients where increased risk
for bleeding is not currently known. The study examines the shorter use of DAPT
in comparison to the usual use after DES implantation.
Study objective
1) Safety: Non inferiority of the BioFreedom* to the Gazelle* Bare Metal Stent
in patients treated with one month DAPT only followed by aspirin alone. The
non-inferiority will be assessed by the composite endpoint of CD, MI and ST at
1 year.
2) Efficacy: Superiority of the BioFreedom* to the Gazelle* Bare Metal Stent as
assessed by TLR at 1 year.
Study design
Prospective, multi center, multi-national, double blinded, randomized, trial
designed to enroll 2456 patients at up to seventy centers worldwide. Patients
will be randomized at 1:1 ratio to the stent treatment. All patients will be
followed for 2 years.
Intervention
The patient will undergo coronary angioplasty as normal and the stent used will
be for:
Group A. Biosensors Gazelle* Bare Metal Coronary Stent: a stent which has not
been covered with a drug. It has been commercially approved (CE Mark
2146002CE01).
Group B. Biosensors BioFreedom* Coronary Stent: is very similar to the Gazelle
stent and is made by the same company, but coated with the drug Biolimus A9*,
which has proved to be efficient in preventing artery re-narrowing.
+ One month of Aspirin plus either Clopidogrel/ Parasugrel/Ticagreolor for
groupe A and group B, followed by single Antiplatelet therapy indefinetely
The post-procedure tests and examination as well as the follow-up will be the
same for both groups and are part of the hospital routine.
Study burden and risks
Before and after the procedure the patient will take two blood-thinning
medications to prevent blood from clotting within the stents. These drugs,
Aspirin and Clopidogrel (or Prasugrel or Ticagrelor), are used routinely
following stent placement.
Patient may also get other medications.
Follow-up: at 1, 2 and 4 months as well as at 1 and 2 years.
Without patient's problems, 2- and 4-month as well as 2-year Follow-Up may be
done over the telephone.
The Follow Up at 1 month and 1 year should be done at the hospital.
Blood samples (about 2 tablespoons) will be collected for the study before
procedure and at discharge.
This will be done whether the patient participate in this study or not and are
routine for the procedure.
For the women of child-bearing potential, a pregnancy test to rule out
pregnancy will be performed up to 7 days before stent placement.
Only testings that are standard of care at the site hospital for patients with
study condition will be performed.
Risk:
A small number of people will have complications from their treatment. The risk
of a problem varies depending on patient overall health and individual heart
condition. As with any treatment of narrowing of one or more coronary artery
lesions, the major complications are
• Death: than 1%
• Stroke: 0.5%
• Heart Attack:2-5%
• Bleeding (major and minor): 2-5% The potential risk of receiving stents
coated with a drug combined with only one month double antiplatelet treatment,
is the risk of a blockage of the stent(s), called stent thrombosis and the
potential risk of heart attack or death due to this blockage. The known risk of
receiving a stent without a drug in comparison to a drug-eluting stent is the
more frequent (up to 20%) re- narrowing of the coronary arteries.
Other risks for both stents include the fact that occasionally coronary
angioplasty cannot be performed because of technical difficulties with the
inability to pass the balloon or stent across the narrowed artery.
During the procedure, X-rays are use to direct the stent to the correct
position. No additional radiation will be used in the study; exposure to the
radiation will be part of the normal care and should carry no extra risks.
High doses of x-ray has the potential to cause skin damage, however, we do not
anticipate this procedure will exceed the accepted threshold.
Benefit:
The information gathered in the study may help to improve the treatment given
to patients with an increased bleeding risk and coronary artery disease in the
future.
Rue de Lausanne 29
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Rue de Lausanne 29
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Listed location countries
Age
Inclusion criteria
Any indication for PCI-S in patients deemed at high risk for bleeding and candidates for 1 month DAPT. This includes candidates with stable angina, silent ischemia, ACS (STEMI and non-STEMI), non-native lesions and in-stent restenosis. Patients must provide written informed consent.
Reasons of unsuitability for > 1 month dual antiplatelet treatment must include one or MORE of the following:
1. Adjunctive oral anticoagulation treatment planned to continue after PCI
2. Age >= 75 years old
3. Baseline Hgb <11 g/dl (or anemia requiring transfusion during the 4 weeks prior to randomization)
4. Any prior intracerebral bleed
5. Any stroke in the last 12 months
6. Hospital admission for bleeding during the prior 12 months
7. Non skin cancer diagnosed or treated < 3 years
8. Planned daily NSAID (other than aspirin) or steroids for >30 days after PCI
9. Planned surgery that would require interruption of DAPT (within next 12 months)
10. Renal failure defined as: Creatinine clearance <40 ml/min
11. Thrombocytopenia (PLT <100,000/mm3)
12. Severe chronic liver disease defined as: patients who have developed any of the following: variceal hemorrhage, ascites, hepatic encephalopathy or jaundice
13. Expected non-compliance to prolonged DAPT for other medical reasons
Exclusion criteria
1. Pregnant and breastfeeding women
2. Patients expected not to comply with 1 month DAPT
3. Patients requiring a planned staged PCI procedure more than one week after the index procedure
4. Procedure planned to require non-study stents, or stand-alone POBA or stand-alone atherectomy
5. Active bleeding at the time of inclusion
6. Reference vessel diameter <2.25 - >4.0mm
7. Cardiogenic shock
8. Compliance with long-term single anti-platelet therapy unlikely
9. A known hypersensitivity or contraindication to aspirin, clopidogrel (or prasugrel, or ticagrelor if applicable), stainless steel, zinc, Biolimus A9TM or a sensitivity to contrast media, which cannot be adequately pre-medicated
10. PCI during the previous 12 months for a lesion other than the target lesion of the index procedure
11. Participation in another clinical trial (12 months after index procedure)
12. Patients with a life expectancy of < 1 year
13. Patients under judicial protection, tutorship or curatorship (for France only)
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 | NCT01623180 |
| CCMO | NL43274.075.13 |