Clinical trial NCT04312555: Alprostadil as an Adjuvant Therapy With Indirect Angiosomal Revascularization in Critical Limb Ischemia.
Official title: Efficacy of Alprostadil as an Adjuvant Therapy With Indirect Angiosomal Revascularization in Patients With Critical Limb Ischemia.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Critical Limb Ischemia
Keywords: CLI
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2020-03-18
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess the efficacy of Alprostadil (Prostaglandin E2) as adjuvant therapy after failure of direct but indirect angiosomal revascularization in patients with critical limb ischemia.

Detailed description: In large number of elderly patients aged between 50 and 75 years, the arterial disease is prevalent (1%-7%). It has a significant impact on the quality of life. Pain, fear of limb loss, increased inactivity, and poor lifestyle choices which finally ended by disability. Disability in turn makes communities and counties carry more efforts and charges.

The incidence of critical limb ischemia (CLI) is increasing, and diabetic patients are especially prone to developing ischemic and neuro-ischemic foot ulcers. Twelve to 25% of diabetic patients may develop a foot lesion over time. Diabetic patients often present with more extensive tissue loss compared to non-diabetic patients. The importance of revascularization of the lower limb in patients with CLI has been well established, and expedited revascularization is mandatory once an ischemic foot ulcer is detected.

Although there is still a role for surgical bypass, over the last several decades the use of endovascular techniques has become more frequent. This development has been made possible by the evolution of endovascular devices and operator skills. The less-invasive endovascular approach is the preferred treatment method, especially in the frail diabetic patient with multiple comorbidities. Incisional wound healing in diabetic patients can also be problematic. In both open and endovascular revascularization there is a clear difference of approach in patients with CLI caused by inflow disease (iliac, femoral, and popliteal disease) and those with (additional) infrapopliteal involvement. Whereas in above-the-knee disease, it is clear that flow in the stenotic or occluded segment needs to be re-established, in below-the-knee (BTK) disease, potentially three vessels can be revascularized, and this poses a therapeutic dilemma. Choosing the correct target for revascularization can present a critical, complex issue in challenging cases, especially when multilevel arterial disease is present. Revascularization can be accomplished by using two approaches: "complete" revascularization (one vessel is better than none, two to three vessels are better than one) or "wound-related" revascularization. With CLI, the healing of an ulcer is blood-flow-dependent and the goal of treatment should be to get the best possible blood supply to the foot (direct revascularization). In practice this is not always feasible, and in order to guide the choice of which BTK vessel should be revascularized, the angiosome concept has been proposed, based on the idea that specific anatomical regions are perfused by specific arteriovenous bundles.

Prostaglandins are potent vasoactive agents with wide variety of other actions - vasodilatation, fibrinolysis and inhibition of platelet aggregation. PG infusion therapy may show a promising results in patients where such new reconstructive procedures are not feasible or failed and also as an adjunctive when there is a residual ischemia after the revascularization procedures.

Eligibility criteria: Inclusion Criteria:

* Subject ≥ 40 years.
* Subject with chronic limb ischemia \[Rutherford classification 4, 5 \& 6\].
* Subject failed to direct revascularization.
* Subject is able and willing to comply with the protocol and to adhere to the follow-up requirements.
* Subject has provided written informed consent.

Exclusion Criteria:

* Subject's age less than 40.
* Imminent or foreseeable amputation
* Subject already had a major amputation on the affected extremity
* Subject has emergent ischemic lesion \[such as gas forming infection\].
* Subject has a known hypersensitivity or contraindication to anticoagulants, anti-platelets, or contrast media, which is not amenable to pre-treatment.
* Subject has a known hypersensitivity or contraindication to Alprostadil.
* Subject is not in the position to be primarily revascularized or refuses surgery.
* Acute ischemia and peripheral vascular disorders of inflammatory or immunologic origin
* Neuropathic or venous ulcers
* Already using vasoactive medication or prostaglandins
* Treatment with prostanoids within 3 months prior to inclusion

Primary outcomes:
measure: Patency
timeFrame: 3 months
measure: Major Adverse Limb Events (MALE)
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Assiut University
name: Ashraf Elnaggar, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Assiut University
name: Hassan Bakr El-Badawy, Prof
role: STUDY_CHAIR
affiliation: Al-Azhar University
name: Mohamed Elsagheer Elhewwy, Prof
role: STUDY_DIRECTOR
References:
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citation: Soderstrom M, Alback A, Biancari F, Lappalainen K, Lepantalo M, Venermo M. Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers. J Vasc Surg. 2013 Feb;57(2):427-35. doi: 10.1016/j.jvs.2012.07.057. Epub 2012 Dec 7.
citation: Alexandrescu V, Hubermont G. Primary infragenicular angioplasty for diabetic neuroischemic foot ulcers following the angiosome distribution: a new paradigm for the vascular interventionist? Diabetes Metab Syndr Obes. 2011;4:327-36. doi: 10.2147/DMSO.S23471. Epub 2011 Aug 22.