The primary objective is to test whether thrombolysis with additional contrast-enhanced ultrasound is applicable in patients with peripheral arterial occlusions. The secondary objectives are to investigate the safety of microbubble and ultrasound…
ID
Source
Brief title
Condition
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main endpoints will be the duration of thrombolysis needed for uninterrupted
flow in the thrombosed native artery or bypass graft with outflow through at
least 1 crural artery and microcirculation of the lower limb as measured by
Laser Doppler Flowmetry on the skin of the lower limb. Furthermore, Severe
Adverse Events (haemorrhagic complications, allergic reactions, in hospital
mortality directly related to the treatment) and amputation-free rate at 6
months.
Secondary outcome
Secondary endpoints will be the success rate, distal thromboembolic
complications, other complications, 30 day mortality rate, conversion to open
surgery, duration of hospital admission, serum fibrinogen concentrations, pain
scores and quality of life.
Background summary
Acute peripheral vascular disease can be caused by a blood clot blocking an
artery in an arm or leg. This is an emergency situation that can result in
amputation or be life threatening if not treated promptly. Infusion of lytic
agents, such as urokinase and alteplase, can restore blood flow by dissolving
the clot as a less invasive alternative to conventional surgical
reconstruction, i.e. thrombolysis. In comparison with the lysis of small
arterial occlusions in for example patients with myocardial infarction, larger
arterial occlusions in vascular surgery patients require higher doses of lytic
agents and infusion over a longer period of time. However, this technique is
time consuming (days), requires repeated angiography for treatment evaluation
risking kidney failure and most importantly is accompanied by the risk on major
bleeding complications, such as stroke. As a result this leads to high
morbidity and mortality rates and a large impact on patient burden. Improvement
of this therapy is therefore highly needed.
A potential accelerater of thrombolytic therapy is contrast-enhanced
ultrasound. Contrast-agents, initially used as diagnostic tool could also be
applied therapeutically to speed up thrombolysis. Their oscillating behavior
could induce mechanical forces on the clot surface making the thrombus more
susceptible to thrombolytics. This could reduce therapy time and lower the
required dose of lytic agents leading to a lower risk of bleeding complications
and decreased patient burden.
Study objective
The primary objective is to test whether thrombolysis with additional
contrast-enhanced ultrasound is applicable in patients with peripheral arterial
occlusions. The secondary objectives are to investigate the safety of
microbubble and ultrasound enhanced intra-arterial thrombolysis and if it is
logistically feasible in our university hospital.
Study design
Phase-II trial: 20 patients will all receive the experimental protocol. The
first 10 patients were evaluated with the use of urokinase as thrombolytic
therapy. Because of manufacturing delivery problems, the Urokinase has been
replaced by Alteplase.
Intervention
The experimental protocol consists of the standard thrombolysis protocol, i.e.
the local placement of a catheter and sheath in the *angio-room* just near the
occlusion or thrombus of the affected artery and infusion of alteplase and
heparin. In this study additional ultrasound contrast-agents will be
intravenously injected and local ultrasound will be applied at the site of
occlusion during the first hour of therapy.
Study burden and risks
The additional burden for patients participating in this study are estimated to
be minimal seen the fact that the experimental protocol is executed during the
first hour of standard thrombolytic treatment. The risk of the application of
ultrasound with contrast is estimated minimal, as the technique has been used
safely in clinical practice as diagnostic tool for years. Furthermore, the
total dose we administer during one hour is lower then safely administered as
bolus injections in humans as reported before without the occurence of adverse
events. The additional measurements during treatment and follow up are
minimally invasive and require little extra time of the patients.
Boelelaan 1117
Amsterdam 1081HV
NL
Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
* Men and women older than 18 years and younger than 85 years old
* Patients with a maximum of 2 weeks complaints due to lower limb ischemia due to
thrombosed/occluded iliofemoral, femoropopliteal or femorocrural native arteries or femoropopliteal or
femorocrural venous or prosthetic bypass grafts
* Anatomic suitability duplex ultrasound in case of iliac occlusion
* Patients fit for thrombolysis i.e. with acute lower limb ischemia class I and IIa according to the
Rutherford classification (see attachment II)
* Patients understand the nature of the procedure and provide written informed consent before enrolment
in the study
Exclusion criteria
* Patients with clinical complaints of acute lower limb ischemia due to thrombosis of the iliofemoral, femoropopliteal or femorocrural native arteries, or femoropopliteal or femorocrural venous or prosthetic bypass grafts more than 2 weeks
* Patients with iliac occlusions anatomically not suitable for duplex ultrasound
* Patients with thrombosed popliteal aneurysms
* Patients with contra-indications for the administration of antiplatelet therapy, anticoagulants or thrombolytics
* Recent (less than 6 weeks) ischemic stroke, cerebral bleeding or myocardial infarction
* Patients with recent (less than 6 weeks) surgery
* Severe hypertension (diastolic blood pressure greater than 110 mm Hg, systolic blood pressure higher than 200 mm Hg)
* Current malignancy or severe comorbid condition with a life expectancy of less than 6 months
* Patients with uncorrected bleeding disorders (gastrointestinal ulcer, menorrhagia, liver failure)
* Women with child-bearing potential not taking adequate contraceptives or currently breastfeeding
* Pregnancy
* Patients who are currently participating in another investigational drug or device study
* Patients younger than 18 years or older than 85 years
* Patients with contra-indications for Luminity microbubbles i.e.
* Hypersensitivity to perflutren or other components of Luminity
* Recent acute coronary syndrome or clinically unstable ischemic cardiac disease, including: evolving or ongoing myocardial infarction, typical angina at rest within last 7 days, significant worsening of cardiac symptoms within last 7 days, recent coronary artery intervention or other factors suggesting clinical instability (for example, recent deterioration of ECG, laboratory or clinical findings), acute cardiac failure, Class III/IV cardiac failure, or severe rhythm disorders
* Patients known to have right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure >90 mmHg), uncontrolled systemic hypertension, and in patients with GOLD Stage IV COPD, diffuse interstitial fibrosis or adult respiratory distress syndrome.
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 |
|---|---|
| EudraCT | EUCTR2014-003469-10-NL |
| CCMO | NL46636.029.14 |