Safety Study of UT-15C SR (Oral Treprostinil) in Patients Undergoing a Lower Limb Endovascular Procedure
Information source: Ochsner Health System
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Critical Limb Ischemia
Intervention: treprostinil dienthanolmine sustained release (Drug); Placebo (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Ochsner Health System Official(s) and/or principal investigator(s): Mark A Grise, M.D., Principal Investigator, Affiliation: Ochsner Clinic Foundation
Summary
In chronic CLI patients who are appropriate candidates for endovascular procedures - and
many patients are not because of their advanced age and disease state - the treatment
regimen may include endovascular procedures such as percutaneous transluminal endovascular
intervention, as well as reconstructive surgical procedures such as grafts or bypasses.
Amputation is a last resort where limb salvage cannot be achieved. Despite the success of
percutaneous intervention for small coronary vessels with lumen diameters less than 3 mm,
similar techniques have had limited success in the lower extremity vessels. Infra-popliteal,
or below the knee endovascular intervention, is commonly plagued by subacute thrombotic
closure and restenosis in as many as 50% of treated patients. As a result of the limited
success, these percutaneous procedures have been reserved for the severest cases whereby
limb loss is imminent without intervention. In this context, the sickest of all patients are
enrolled in these trials and poor outcomes are common regardless of the intervention. Agents
that promote intracellular cAMP accumulation, including prostacyclin analogues and
phosphodiesterase inhibitors, suppress smooth muscle proliferation, promote vasodilatation
and inhibit platelet aggregation. These properties suggest that prostacyclin analogues such
as treprostinil will be useful adjuncts to peripheral endovascular intervention and perhaps
increase the number of patients with CLI that can benefit from peripheral endovascular
intervention. An orally available prostacyclin analogue could represent an important
treatment advance in the prevention of restenosis following infrapopliteal angioplasty. In
the present study, the safety and efficacy of oral UT-15C sustained release (SR) tablets
will be compared to placebo in patients with CLI undergoing an infra-popliteal endovascular
intervention.
Clinical Details
Official title: A Randomized, Single-Center, Placebo Controlled Study To Assess the Safety of UT-15C (Treprostinil Diethanolamine) Sustained Release (SR) in Patients Undergoing an Infra-Popliteal Endovascular Intervention for the Treatment of Critical Limb Ischemia
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: To assess the tolerability and safety of UT-15C SR as compared to placebo tablets in subjects with critical limb ischemia (CLI) undergoing an infra-popliteal endovascular intervention procedure.
Secondary outcome: To assess the efficacy of UT-15C SR as compared to placebo tablets on measures of clinical outcomes in subjects with critical limb ischemia (CLI) undergoing an infra-popliteal endovascular intervention procedure.
Detailed description:
This study is a randomized, placebo controlled, single-center, evaluation of the safety and
efficacy of UT-15C SR compared to placebo in patients with CLI with a planned
infra-popliteal endovascular intervention procedure. Conventional therapy should be
continued for all patients in the study. Conventional therapy is defined as the customary
best medical practice at this investigative site for CLI, including analgesics for rest
pain, debridement and wound care for ischemic wounds, etc., as long as such care meets the
other requirements of the study and does not include prohibited therapies or investigational
medications. A total of 20 patients will be prospectively randomized (1: 1) to conventional
treatment and placebo therapy in conjunction with an endovascular procedure or conventional
treatment and UT-15C SR therapy in conjunction with an infrapopliteal endovascular
procedure. Treatment is UT-15C sustained release (SR) tablets (1. 0 mg dosage strength) or
placebo. Treatment will be initiated at 1 mg twice daily with dose escalation of an
additional 1 mg twice daily every 5 days if clinically indicated based upon the presence of
known prostacyclin adverse events or adverse events that in the opinion of the investigator
are attributable to UT-15C SR. Doses should be maximized throughout the Treatment Phase up
to a maximum dose of 5 mg twice daily at the end of 12-weeks. Patients will return to the
institution for the endovascular procedure at least 4 days after starting study drug and
continue study drug, throughout the endovascular procedure and to Week 12. All patients will
return to the clinic at Weeks 2, 6 and 12 for Treatment Phase assessments, and then Weeks 26
and 52 for follow-up assessments.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Be 18 or older.
2. Have an anticipated infra-popliteal endovascular intervention.
3. Have a diagnosis of stage IIb- IVa (Fontaine) or stage 3- 5 (Rutherford scale) CLI
due to documented peripheral arterial disease (Appendix E)
4. If female, be physiologically incapable of childbearing or practicing acceptable
methods of birth control.
5. Have signed an appropriate informed consent for participation in this study.
Exclusion Criteria:
1. Have had a previous endovascular intervention or stenting on the target limb.
2. Be hemodynamically unstable, on hemodialysis for end stage renal failure, or have
acute renal, cardiac or pulmonary failure.
3. Have a history of intracranial bleeding, bleeding ulcer, urinary tract bleeding; or
bleeding due to significant trauma within six weeks prior to study entry.
4. Have a life-threatening malignancy requiring aggressive chemotherapy.
5. Have any condition or laboratory value which, based on information in the UT-15C SR
investigators' brochure, would constitute an unacceptable risk to the patient's
safety, in the opinion of the investigator.
6. Have unstable psychiatric status or be mentally incapable of understanding the
objectives, nature or consequences of the trial.
7. Have a known hypersensitivity to prostacyclin.
8. Have participated in any investigational trial within 30 days of study drug
initiation.
9. Have been a non-responder to chronic (>30 days) prostanoid treatment, or have
completed a chronic trial of prostanoid therapy within 30 days of study drug
initiation.
10. Be a pregnant or nursing woman.
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Locations and Contacts
Ochsner Clinic Foundation, New Orleans, Louisiana 70121, United States
Additional Information
Starting date: March 2008
Last updated: May 13, 2011
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