Alprostadil as an Adjuvant Therapy With Indirect Angiosomal Revascularization in Critical Limb Ischemia.

Efficacy of Alprostadil as an Adjuvant Therapy With Indirect Angiosomal Revascularization in Patients With Critical Limb Ischemia.

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.

Study Overview

• Status: Unknown
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Drug: Alprostadil

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Seif Eleslam Tawfik, Resident; Phone Number: +201008011018; Email: dr.seifalkadi@yahoo.com
• Study Contact Backup: Name: Ashraf Elnaggar, MD; Phone Number: 01005212168; Email: Ashrafnagar@aun.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patency	Maintaining vessel patency without restenosis or need for re-intervention	3 months
Major Adverse Limb Events (MALE)	repeated endovascular therapy, surgical revision, or major amputation during follow up period	3 months

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Ashraf Elnaggar, Dr, Assiut University; Study Chair: Hassan Bakr El-Badawy, Prof, Assiut University; Study Director: Mohamed Elsagheer Elhewwy, Prof, Al-Azhar University

Publications and helpful links

General Publications

• Kroger K, Hwang I, Rudofsky G. Recanalization of chronic peripheral arterial occlusions by alternating intra-arterial rt-PA and PGE1. Vasa. 1998 Feb;27(1):20-3.
• Bucci M, Iacobitti P, Laurora G, Cesarone MR. [Analysis of costs and results of prostaglandin (PGE1 alpha-cyclodestrin) therapy of peripheral arterial diseases]. Minerva Cardioangiol. 1998 Oct;46(10 Suppl 1):9-15. Italian.
• Palena LM, Garcia LF, Brigato C, Sultato E, Candeo A, Baccaglini T, Manzi M. Angiosomes: how do they affect my treatment? Tech Vasc Interv Radiol. 2014 Sep;17(3):155-69. doi: 10.1053/j.tvir.2014.08.004.
• Neville RF, Sidawy AN. Surgical bypass: when is it best and do angiosomes play a role? Semin Vasc Surg. 2012 Jun;25(2):102-7. doi: 10.1053/j.semvascsurg.2012.04.001.
• Iida O, Soga Y, Hirano K, Kawasaki D, Suzuki K, Miyashita Y, Terashi H, Uematsu M. Long-term results of direct and indirect endovascular revascularization based on the angiosome concept in patients with critical limb ischemia presenting with isolated below-the-knee lesions. J Vasc Surg. 2012 Feb;55(2):363-370.e5. doi: 10.1016/j.jvs.2011.08.014. Epub 2011 Nov 1.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2020
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): October 1, 2021

Study Registration Dates

• First Submitted: March 16, 2020
• First Submitted That Met QC Criteria: March 16, 2020
• First Posted (Actual): March 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 20, 2020
• Last Update Submitted That Met QC Criteria: March 18, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: CLI
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia; Vasodilator Agents; Urological Agents; Platelet Aggregation Inhibitors; Alprostadil
• Other Study ID Numbers: Alprostadil with CLI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No