Critical Limb IschemiaPhase 4NCT04312555
Alprostadil as an Adjuvant Therapy With Indirect Angiosomal Revascularization in Critical Limb Ischemia.
A Phase 4 study testing Alprostadil in people with Critical Limb Ischemia, run by Assiut University.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Critical Limb Ischemia
- What is being tested?
- Alprostadil
- Type of treatment
- Injection or infusion
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2020to 1 Oct 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: 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.
Read the 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.
- Conditions
- Critical Limb Ischemia
- Being tested
- Alprostadil
- Keywords
- CLI
- Medical subject headings
- Chronic Limb-Threatening Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlprostadilDrug
Alprostadil intravenous administration. (0.5 mg/1ml of Alprostadil + 49cm saline 0.9%) and 4 cm direct intravenously / 8 hours
What is being measured
The primary outcome is the main question the study is designed to answer.
Patency
Maintaining vessel patency without restenosis or need for re-intervention
Measured: 3 months
Major Adverse Limb Events (MALE)
repeated endovascular therapy, surgical revision, or major amputation during follow up period
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2020
- Study start1 Apr 2020 (estimated)
- Primary completion1 Apr 2021 (estimated)
- Study completion1 Oct 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Critical Limb IschemiaStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Seif Eleslam Abdelhafiz Tawfik Ali, Assiut University
- Investigators
- Ashraf Elnaggar, Dr, Principal investigator, Assiut UniversityHassan Bakr El-Badawy, Prof, Study chair, Assiut UniversityMohamed Elsagheer Elhewwy, Prof, Study director, Al-Azhar University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04312555
- Sponsor's protocol ID
- Alprostadil with CLI
- Status last verified
- Mar 2020
- First submitted
- 16 Mar 2020
- Last updated
- 20 Mar 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 9540428Bucci 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.
PubMed 10658439Palena 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.
PubMed 25241316Neville 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.
PubMed 22817860Iida 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.
PubMed 22051875Soderstrom 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.
PubMed 23219512Alexandrescu 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.
PubMed 21969804
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Alprostadil as an Adjuvant Therapy With Indirect Angiosomal Revascularization in Patients With Critical Limb Ischemia.
- ClinicalTrials.gov ID
- NCT04312555
- Acronym / sponsor ID
- Alprostadil with CLI
- Conditions
- Critical Limb Ischemia
- Keywords
- CLI
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Apr 2020 (estimated)
- Primary completion
- 1 Apr 2021 (estimated)
- Study completion
- 1 Oct 2021 (estimated)
- First posted
- 18 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlprostadilAlprostadil intravenous administration. (0.5 mg/1ml of Alprostadil + 49cm saline 0.9%) and 4 cm direct intravenously / 8 hours | Drug | – |
Primary outcome
Patency
Time frame: 3 months
Maintaining vessel patency without restenosis or need for re-intervention
Major Adverse Limb Events (MALE)
Time frame: 3 months
repeated endovascular therapy, surgical revision, or major amputation during follow up period
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2020.
- Background: PubMed 9540428Kroger 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.
- Background: PubMed 10658439Bucci 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.
- Background: PubMed 25241316Palena 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.
- Background: PubMed 22817860Neville 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.
- Background: PubMed 22051875Iida 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.
- Background: PubMed 23219512Soderstrom 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.
- Background: PubMed 21969804Alexandrescu 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashraf Elnaggar, Dr principal investigator
Assiut University
Hassan Bakr El-Badawy, Prof study chair
Assiut University
Mohamed Elsagheer Elhewwy, Prof study director
Al-Azhar University
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alprostadil in people with Critical Limb Ischemia, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Seif Eleslam Tawfik, Resident (+201008011018, dr.seifalkadi@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patency (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04312555, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2020.