Combining gene therapy with endovascular treatment for severe limb ischemia

Multicenter Randomized Prospective Controlled Trial of the Clinical Effectiveness of a Best Endovascular Treatment Versus a Best Endovascular Treatment in Combination With Gene Therapy for Severe Limb Ischemia

This study is testing whether adding gene therapy to standard treatment can help people with severe leg circulation problems avoid amputations and improve their outcomes.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 386 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Amur State Medical Academy (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Blagoveshchensk, Amur Oblast)
• Trial ID: NCT06473740 on ClinicalTrials.gov

What this trial studies

This trial investigates the effectiveness of combining endovascular treatment with gene therapy using a specific plasmid DNA to treat patients with severe lower limb ischemia. It aims to compare the outcomes of this combined approach against standard endovascular treatment alone. The study will assess both immediate and long-term results, focusing on the rates of re-interventions and amputations. By enrolling patients with critical ischemia, the trial seeks to provide insights into new minimally invasive treatment options.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with severe ischemia of the lower extremity and no prior surgical interventions in the affected area.

Not a fit: Patients with non-atherosclerotic causes of peripheral artery disease or those with gangrene may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the need for re-interventions and high amputations in patients with severe limb ischemia.

How similar studies have performed: While this approach is novel, previous studies have shown varying success rates for endovascular treatments in similar patient populations.

Eligibility criteria

Inclusion Criteria:

1. Men and women 18 years of age and older;
2. Atherosclerotic infrainguinal disease of the peripheral arteries (occlusive-stenotic lesion below the inguinal fold);
3. Severe ischemia of the lower extremity, characterized by pain at rest or a non-healing ischemic ulcer, which corresponds to Rutherford categories 4-5 and Fontaine grades III-IV;
4. Without any previous surgical intervention of the ipsilateral n/a below the inguinal fold;
5. Suitable for endovascular treatment according to researchers;
6. Adequate inflow through the aorto-iliac segment;
7. Willingness to comply with the study protocol, attend follow-up examinations, comply with all instructions and provide written informed consent.

Non-inclusion criteria:

1. Infrainguinal disease of peripheral arteries of non-atherosclerotic origin (aortoarteritis, thromboangiitis, congenital anomalies, vascular injuries, etc.) or acute ischemia;
2. Severe ischemia of the lower limb, characterized by gangrene (Rutherford category 6);
3. The presence of a popliteal aneurysm (\>2.0 cm) on the area of interest;
4. Life expectancy \<2 years, for reasons not related to occlusive-stenotic disease of the arteries of the n/c;
5. Planned high amputation on the ipsilateral lower extremity within 4 weeks after the planned endovascular procedure;
6. Hypersensitivity to any components included in the study drug;
7. Previous surgical intervention below the inguinal fold (open vascular, endovascular or hybrid treatment);
8. Open treatment of the inflow tract of the ipsilateral lower limb within 6 weeks before enrollment in the study (aortofemoral, iliofemoral, axillofemoral, femorofemoral bypass);
9. Current chemotherapy or radiation therapy;
10. Pregnancy or lactation;
11. Cases of AMI, CABG or stroke within 6 weeks before enrollment in the study;
12. An absolute contraindication to the use of iodinated contrast agent due to a previous severe allergic reaction (laryngospasm, bronchospasm, cardiorespiratory shock or their equivalent);
13. Participation in another clinical trial within the previous 30 days;
14. The patient's inability to understand the essence of the study;
15. Refusal of the patient to sign informed consent.

Exclusion Criteria:

1. Refusal of the patient to further participate in the study;
2. Use of drugs from the list of prohibited concomitant therapy;
3. The use of any other concomitant therapy that, in the opinion of the investigator, may interfere with the assessment of the effectiveness and safety of the investigational medicinal product and/or distort the results of the study;
4. Onset of pregnancy;
5. Injuries and damage to the ipsilateral lower limb, which, in the opinion of the investigator, may interfere with the assessment of the effectiveness and safety of the study drug and/or distort the results of the study;
6. The presence of an adverse event that, in the opinion of the investigator, indicates that continued participation in the study poses an unacceptable risk for the patient.
7. The occurrence or identification of concomitant diseases that prevent the patient's further participation in the clinical trial, in the opinion of the investigator.

Where this trial is running

Blagoveshchensk, Amur Oblast

• Amur State Medical Academy — Blagoveshchensk, Amur Oblast, Russia (RECRUITING)

Study contacts

• Principal investigator: Alrxander Korotkikh, PhD — Amur State Medical Academy
• Study coordinator: Alrxander Korotkikh, PhD

Conditions: Severe Lower Limb Ischemia, gene therapy, amputation, severe lower limb ischemia, endovascular treatment, stenting, balloon angioplasty