To demonstrate that the use of US-accelerated catheter-derived thrombolysis in patients with recently (less than 7 weeks) thrombosed infra-inguinal bypass grafts or native arteries with half the dose urokinase (50.000 IU/h) will significantly reduce…
ID
Source
Brief title
Condition
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Occurrence of hemorrhagic complications.
Secondary outcome
1. Technical success defined as >95% lysis of thrombus within 48 hours
2. Duration of catheter-derived thrombolysis needed for uninterrupted flow in
the thrombosed infra-inguinal bypass graft or native artery with outflow via at
least one crural artery
3. Amount of Urokinase (in IU) needed for uninterrupted flow.
4. 30-day mortality
5. 30-day patency of the target artery or bypass, as evidenced by Colour Flow
Doppler Ultrasound (Duplex)
6. Conversion to open surgery
7. Distal thrombo-embolic complications
Background summary
Thrombosis of an infra-inguinal bypass graft or the native lower leg arteries
has been associated with a substantial need for amputations and significant
morbidity and mortality. Traditional therapy consisted of surgical
interventions like thrombectomy and bypass revision, whereas currently
catheter-directed thrombolysis is preferred. Advantages of catheter-directed
thrombolysis as compared to surgery are: less-invasive character, gentler clot
removal, clearing out and visualizing the small distal runoff vessels and
eventual collaterals. Moreover the underlying lesion can be treated by
endovascular means and inflow and outflow arteries can be optimized. Drawbacks
might be: higher costs, longer time needed to revascularization compared to
surgery, thrombolysis induced hemorrhagic complications, a small but
significant incidence of stroke, and renal dysfunction related to repeated
angiography.
To reduce these limitations reduction of thrombolytic therapy time will be
necessary. Based on available literature US-accelerated thrombolysis has been
shown to reduce therapy time of patients with deep vein thombosis by increasing
clot permeability to the thrombolytic agent. A similar result was seen in a
recent recies of patients with an acute obstruction of the native lower limb
arteries.
Recently, the Dutch multicentre DUET I trial has been published. In this trial
US-enhanced thrombolysis was compared to standard catheter directed
thrombolysis for patients with lower limb arterial thrombus}.
Major conclusions of the DUET I trial are: 1.US-accelerated thrombolysis
significantly reduces the duration of thrombolysis time compared to standard
catheter directed thrombolysis, 2.US-enhanced thrombolysis significantly
decreases the amount of urokinase without increase of complications. However,
still the amount of adverse events including bleeding complications was around
28%.
Study objective
To demonstrate that the use of US-accelerated catheter-derived thrombolysis in
patients with recently (less than 7 weeks) thrombosed infra-inguinal bypass
grafts or native arteries with half the dose urokinase (50.000 IU/h) will
significantly reduce hemorrhagic complication rate compared with US-accelerated
catheter-derived thrombolysis with the standard dose urokinase (100.000 IU /h)
with comparable technical success rates.
Study design
multicentre randomized controlled trial
Intervention
Group A (US-accelerated thrombolysis with 100.000 IU urokinase/h):
During angiography an US-enhanced thrombolysis delivery catheter will be
navigated into the thrombosed arterial segment over a guide wire in such a way
that the treatment zone traverses the entire clot and the tip lies distal to
the thrombus in a run off artery.
After final positioning, the guide wire will be exchanged for a matching US
core wire and thrombolytic therapy will be started. Likewise a control
angiography will be performed every 6 hours by day, or whenever clinically
needed.
Group B (US-accelerated thrombolysis with 50.000 IU urokinase/h ):
Intervention will be similar to group A, but US-accelerated thrombolysis will
be performed with 50.000 IU urokinase/h.
Study burden and risks
Urokinase in combination with the EKOS endowave system (EKOS corporation,
Bothell, WA, USA) has been extensively used previously for the treatment of
venous thrombosis as well as arterial thrombosis.
The only difference between the two groups is the dose Urokinase used. It is
expected that the use of half the dose of Urokinase will bring no extra risks
for the patients in that group.
If not participating in this trial, patients will be treated with
US-accelerated thrombolysis therapy with the common dose of 100.000 IU
urokinase/h.
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Listed location countries
Age
Inclusion criteria
1. Patients with recently (less than 7 weeks) thrombosed femoro-popliteal or femoro-crural native arteries with ischemic complaints.
2. Patients with recently (less than 7 weeks) thrombosed femoro-popliteal or femoro-crural venous or prosthetic bypass grafts with ischemic complaints.
3. Limb ischemia class I and IIa according to the acute Rutherford classification.
4. Patients >18 years and < 85 years old.
5. Patients understand the nature of the procedure and provide written informed consent, prior to enrolment in the study
Exclusion criteria
1. Patients with isolated common femoral artery thrombosis including the origin of the superficial femoral artery and profunda femoral artery.
2. Patients with clinical complaints of lower limb ischemia due to thrombosis of femoro-popliteal or femoro-crural native arteries or femoro-popliteal and femoro-crural bypass grafts >7 weeks.
3. Patients with acute lower limb ischemia class IIb and III according to the acute Rutherford classification (see below).
4. Patients for whom antiplatelet therapy, anticoagulants or thrombolytic drugs are contraindicated
5. Recent (< 6 weeks) ischemic stroke or cerebral bleeding
6. Patients with recent (<6 weeks) surgery
7. Severe hypertension (diastolic blood pressure >110 mmHg, systolic blood pressure >200 mmHg)
8. Current malignancy
9. Patients with a history of prior life-threatening contrast medium reaction
10. Patients with uncorrected bleeding disorders (GI ulcera, mennorrhagia, liver failure)
11. Female patients of child bearing age not taking adequate contraceptives or currently breastfeeding.
12. Pregnancy
13. Any patient considered to be hemodynamically unstable at onset of procedure
14. Patients refusing treatment.
15. Patients currently participating in another investigational drug or device study that have not completed the entire follow up period.
16. Patients < 18 years or >85 years old.
17. Severe co-morbid condition with life expectancy < 1 month
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 |
|---|---|
| EudraCT | EUCTR2015-002161-27-NL |
| CCMO | NL49466.100.15 |
| OMON | NL-OMON19905 |