Evaluation of MST-188 in Acute Lower Limb Ischemia

Conditions: Acute Lower Limb Ischemia
MedDRA version: 17.0Level: LLTClassification code 10066920Term: Leg ischemiaSystem Organ Class: 100000004866
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2014-000377-40-CZ

Lead Sponsor: Mast Therapeutics, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 60

Inclusion Criteria

1. Written documentation of informed consent
2. Age =30 and <80 years
3. Symptoms consistent with acute ischemia in the target lower limb of =14 days’ duration and classified as Rutherford Category IIa or IIb
4. Subject is hospitalized or in the process of admission for the treatment of acute limb ischemia (ALI)
5. Angiographic confirmation of thrombotic lower limb arterial occlusion =10 cm in length
6. Planned recombinant tissue plasminogen activator (rt-PA) intra-arterial, catheter-directed thrombolytic therapy
7. Target lower limb transcutaneous oxygen tension (TcPO2) =40 mmHg
8. Ankle-brachial index (ABI) =0.60 in the target lower limb or, if vessels are incompressible as defined by ABI =1.40 then a toe-brachial index (TBI) =0.50
9. If sexually active, the subject agrees to use reliable contraception while participating in this study and for at least 30 days after discontinuation of blinded study drug infusion
10. If the subject is female and of child-bearing potential, must have negative pregnancy test (urine or serum)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 27
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion Criteria

1. Prosthetic bypass graft occlusion within 1 month of implantation or autogenous graft occlusion within 6 months of placement
2. Prior major amputation in the target limb
3. Inability to place a guidewire to the distal end of the occluding thrombus and position an infusion catheter into the thrombus
4. Thrombotic occlusion limited to the infrapopliteal arteries
5. Occlusion of all of the following tibial arteries on the baseline angiogram: anterior tibial, posterior tibial and peroneal
6. Thrombosis of or embolization deemed to be from a popliteal aneurysm by investigator
7. Motor loss with inability to dorsiflex the foot
8. Rhabdomyolysis and/or myoglobinuria
9. Embolization as the suspected cause of the arterial occlusion
10. Treatment with a thrombolytic agent within the last 48 hours
11. Subject has a known or suspected bleeding diathesis
12. Intracranial or spinal surgery or severe intracranial trauma within the last 3 months
13. History of hemorrhagic stroke, known intracranial neoplasm, aneurysm, or arteriovenous malformation
14. Thrombotic or embolic stroke within 6 months or transient ischemic attack within 3 months
15. Major surgery, intraocular surgery, organ biopsy, lumbar puncture, or puncture of an incompressible artery in the last 10 days
16. New York Heart Association Class IV congestive heart failure
17. Active gastrointestinal or other active organ bleeding
18. Uncontrolled arterial hypertension with systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg
19. Hemoglobin <8 g/dL
20. Subject’s international normalized ratio (INR) >1.7 and unable to be corrected prior to gaining arterial access
21. Subject has platelet count <75,000/mm3
22. Subject has hepatic dysfunction defined by alanine aminotransferase (ALT) >3-fold the institution’s upper limit of normal
23. Subject has a serum creatinine value >1.5 mg/dL or is on dialysis
24. Subject is pregnant or nursing
25. Current vascular graft infection
26. Subject is already hospitalized for any condition other than acute lower limb ischemia in the target limb
27. Subject is currently receiving another investigational drug or has received any investigational drug within 30 days prior to randomization
28. Any contraindications for receiving rt-PA, anticoagulants, or contrast media
29. Subject is otherwise not an appropriate study subject, in the Investigator's judgment
30. Subject has been previously randomized in the present trial or any prior MST-188 clinical trial