This study has been transitioned to CTIS with ID 2024-518122-33-00 check the CTIS register for the current data. The primary aim of the GENPAD study is to evaluate the ability of genotype-guided antithrombotic treatment to reduce adverse clinical…
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the occurrence of adverse clinical events related to
arterial thrombosis at 24 months, including death from any cause, major adverse
cardiovascular events (MACE) and major adverse limb events (MALE).
MACE is defined as the composite of myocardial infarction, stroke, TIA and CV
death.
MALE is defined as the composite of:
- Acute limb ischemia: limb-threatening ischemia that is confirmed by using
limb hemodynamic parameters or imaging and leading to an acute vascular
intervention within 30 days of onset of symptoms.
- Chronic limb ischemia: continuing ischemic limb, foot, or digit pain leading
to hospitalization and intervention and not meeting the definition of acute
limb ischemia; or participants with Rutherford classification3 IV, V or VI at
baseline who had a peripheral vascular intervention over the course of the
trial.
- Peripheral vascular interventions not meeting the definition for acute limb
ischemia or chronic limb ischemia.
Peripheral vascular interventions include pharmacological interventions
(heparin, thrombolysis), peripheral artery surgery/reconstruction, peripheral
artery angioplasty/stent, and (major or minor) amputation.
Major vascular amputation is defined as an amputation above the forefoot due to
a vascular event.
Secondary outcome
Secondary endpoints are the occurrence of the separate elements of the primary
composite outcome at 24 months.
The secondary safety outcome will be major and clinically relevant minor
bleeding complications.
Major bleeding is defined according to the International Society on Thrombosis
and Haemostasis (ISTH) criteria and include
- fatal bleeding,
- symptomatic bleeding into a critical organ
- bleeding causing a fall in hemoglobin level of 20 g L-1 (1.24 mmol L-1) or
more or leading to transfusion of two or more units of whole blood or red cells
- bleeding into a surgical site requiring a second intervention.
All non-major bleedings will be considered minor. Minor bleedings will be
further divided into those that are clinically relevant and those that are not.
A clinically relevant minor bleeding leads to at least one of the following:
- hospitalization (including presentation to an acute care facility without an
overnight stay)
- a physician guided medical or surgical treatment for bleeding
- a change in antithrombotic treatment.
Background summary
In the Netherlands, 1.1 million people have peripheral arterial disease of
which 85,000 patients have symptomatic peripheral arterial disease, such as
intermittent claudication, pain at rest or gangrene. Patients with peripheral
arterial disease are at increased risk of cardiovasculair events - i.e.
myocardial infarction, stroke, limb ischemia or death. International PAD
guidelines recommend the use of clopidogrel 75mg once daily for secondary
prevention of cardiovascular events. Clopidogrel, however, is a prodrug which
need to be metabolized by the enzym CYP2C19 to its active metabolite. Thirty
per cent of patients with peripheral arterial disease receiving clopidogrel
75mg once daily is carrying one or two CYP2C19 loss-of-function allele(s) and
do not or to a limited extent convert the prodrug into active metabolites, and
are therefore at increased risk of adverse cardiovascular events.
Study objective
This study has been transitioned to CTIS with ID 2024-518122-33-00 check the CTIS register for the current data.
The primary aim of the GENPAD study is to evaluate the ability of
genotype-guided antithrombotic treatment to reduce adverse clinical events
related to arterial thrombosis in patients with peripheral arterial disease.
Secondary aims are to evaluate the ability of genotype-guided antithrombotic
treatment to reduce the separate elements of the primary composite outcome and
to assess the risk of clinically relevant bleedings in patients allocated to
the genotype-guided antiplatelet treatment versus standard clopidogrel
prescription.
Study design
A randomized, controlled, open label, multicenter study.
Intervention
Intervention: Testing for carriage of the CYP2C19*2 and *3 allele, i.e.
loss-of-function (LOF) alleles, followed by a genotype guided antithrombotic
treatment with either clopidogrel 75mg once daily (normal metabolizers),
clopidogrel 75mg twice daily (intermediate metabolizers), or low-dose
rivaroxaban plus acetylsalicylic acid (poor metabolizers).
Comparator: All patients receive clopidogrel 75mg once daily without
pharmacogenetic guidance.
Study burden and risks
The burden is one visit to the outpatient clinic of 30 minutes or a
prolongation of a regular visit to the outpatient clinic with 30 minutes.
Additionally, paricipants will be sent questionnaires, two to five times,
dependent on the duration of study follow-up, of 30 minutes each time. 85% of
the research population will not have any risks associated with participation.
For the 30% of the intervention group with one or two loss-of-function
allele(s), risks associated with participation are the possible side effects of
increased dose of clopidogrel or the possible side effects of acetylsalicylic
acid and rivaroxaban.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
- age > 16 years
- obtained written informed consent
- indication for monotherapy clopidogrel 75mg once daily
- ankle-brachial index < 0.9 and/or toe brachial index < 0.5
- current or previous symptoms due to insufficient vascularization of one or
two lower extremities, including intermittent claudication, pain at rest and/or
gangrene (Rutherford category 1-6)
- consulting a vascular surgeon for diagnosis, treatment and/or follow-up of
PAD symptoms
Exclusion criteria
- known CYP2C19*2 and *3 status
- treated with coumarins, Non-vitamin K Oral Anti-Coagulants, unfractionated
heparin, low molecular weight heparins or double antiplatelet therapy for other
indications
- contraindication for clopidogrel, acetylsalicylic acid and/or rivaroxaban
- life expectancy of less than 1 year
- pregnant or breastfeeding women
- unable to give informed consent
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
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-518122-33-00 |
| EudraCT | EUCTR2020-004913-11-NL |
| CCMO | NL75567.091.20 |