Seltoplasmid Plus Revascularization for Diabetic Infrapopliteal Chronic Limb-Threatening Ischemia
17. September 2026 aktualisiert von: jingyong huang, First Affiliated Hospital of Wenzhou Medical University
A Multicenter, Randomized, Open-Label, Controlled Trial to Evaluate the Safety and Efficacy of Seltoplasmid Injection Combined With Revascularization for Chronic Limb-Threatening Ischemia Caused by Infrapopliteal Artery Disease in Patients With Diabetes
The goal of this clinical trial is to learn whether Seltoplasmid Injection can improve outcomes after lower-extremity revascularization. Revascularization is a procedure used to restore blood flow to the leg. The study will include adults with type 2 diabetes, a foot ulcer caused by poor blood flow, and disease mainly affecting the arteries below the knee.
The main questions are:
- Does adding Seltoplasmid lower the risk of major amputation, another procedure to restore blood flow, or death?
- What medical problems occur after treatment with Seltoplasmid? About 180 participants will undergo standard lower-extremity revascularization. After the procedure, eligible participants will be assigned by chance to one of two groups. One group will receive Seltoplasmid plus standard care. The other group will receive standard care alone.
Participants in the Seltoplasmid group will receive injections into the muscles of the affected lower leg. The injections will be given on Day 0, Day 14, and Day 28.
Participants will be followed for 12 months. Researchers will also assess wound healing, survival without amputation, heart and blood vessel problems, pain, and blood flow in the affected leg.
Studienübersicht
Status
Noch keine Rekrutierung
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
Chronic limb-threatening ischemia in patients with diabetes is commonly associated with diffuse, calcified, and multilevel infrapopliteal arterial disease. In patients with ischemic diabetic foot ulcers, revascularization is recommended to restore blood flow, support wound healing, and reduce the risk of limb loss. However, restoration of patency in the main arteries does not always result in adequate perfusion of the distal tissue. Persistent microvascular dysfunction, impaired collateral formation, endothelial dysfunction, inflammation, infection, neuropathy, and abnormal wound-repair responses may continue after technically successful revascularization. Restenosis, repeat revascularization, delayed wound healing, major amputation, cardiovascular events, and death therefore remain important residual risks.
Seltoplasmid Injection is a plasmid-based gene therapy designed to produce local expression of two human hepatocyte growth factor isoforms. Hepatocyte growth factor activates c-Met-dependent signaling pathways involved in endothelial-cell survival, migration, angiogenesis, collateral-vessel development, microvascular repair, and tissue regeneration. Previous clinical studies in patients with severe lower-extremity ischemia have shown a potential benefit for ischemic ulcer healing. However, those studies primarily involved patients who were unsuitable for revascularization or in whom revascularization had produced an inadequate result.
Revascularization and Seltoplasmid Injection may have complementary biological effects. Revascularization restores blood flow and perfusion pressure through the main arterial pathway, whereas locally expressed hepatocyte growth factor may support distal collateral formation, microvascular perfusion, endothelial repair, and wound healing. This combined strategy is intended to address both macroscopic arterial obstruction and persistent impairment of distal tissue perfusion. Nevertheless, the clinical benefit and safety of administering Seltoplasmid Injection after revascularization have not been established in an adequately controlled randomized study.
This investigator-initiated trial is designed to evaluate the benefit-risk profile of this combined strategy in a high-risk population with diabetes, Rutherford category 5 chronic limb-threatening ischemia, ischemic foot ulceration, and predominantly infrapopliteal arterial disease. Randomization will occur only after completion of the index revascularization procedure and postoperative confirmation of eligibility and safety. This design ensures that treatment assignment cannot influence the revascularization procedure and excludes participants who cannot complete the procedure or do not meet the prespecified postoperative safety conditions.
The trial is open-label because the experimental group receives multiple intramuscular injections and the control group does not receive placebo injections. To reduce potential assessment bias, suspected primary endpoint events will be adjudicated by an independent clinical event committee whose members are blinded to treatment assignment. Standardized definitions will be used for major amputation, clinically driven target-limb revascularization, ulcer healing, cardiovascular events, and other clinical outcomes. Wound assessments and photographs, vascular examinations, and tissue-perfusion measurements will be performed using prespecified procedures whenever possible.
Seltoplasmid use after completed revascularization is outside its currently approved indication in China. Participants will be specifically informed of this off-label use, the uncertainty regarding additional benefit, the possibility of unknown risks, and the potential for increased injection-site bleeding or hematoma during antiplatelet or other antithrombotic treatment. Safety will be monitored throughout the study. An independent Data Monitoring Committee will periodically review accumulating safety information and may recommend continuation, modification, temporary suspension, or termination of the study in accordance with its charter.
The study is intended to determine whether adding Seltoplasmid Injection to contemporary revascularization and standardized background care can improve clinically meaningful limb and survival outcomes, wound healing, pain, and distal tissue perfusion without introducing unacceptable safety risks. The findings may provide evidence regarding a combined treatment strategy that targets both large-vessel blood flow and persistent microvascular impairment after infrapopliteal revascularization.
Studientyp
Interventionell
Einschreibung (Geschätzt)
180
Phase
- Phase 4
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienkontakt
- Name: Jingyong Huang
- Telefonnummer: +8613600672565
- E-Mail: 43737136@qq.com
Studieren Sie die Kontaktsicherung
- Name: Xiang Su
- Telefonnummer: +8613616631391
- E-Mail: suxiang0815@163.com
Studienorte
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Zhejing
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Hangzhou, Zhejing, China, 310003
- The First Affiliated Hospital, Zhejiang University School of Medicine
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Kontakt:
- Hongkun Zhang, M.D., Ph.D.
- Telefonnummer: +86-571-87236745
- E-Mail: doczhk@163.com
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Hangzhou, Zhejing, China, 310006
- Hangzhou First People's Hospital
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Kontakt:
- Xin Fang, M.D., Ph.D.
- Telefonnummer: +86-571-56007032
- E-Mail: hzsyyy1@163.com
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Hangzhou, Zhejing, China, 310014
- Zhejiang Provincial People's Hospital
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Hangzhou, Zhejing, China, 310016
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
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Kontakt:
- Jing Yang, M.D., Ph.D.
- Telefonnummer: 86-571-86090073
- E-Mail: Yangjinsir@163.com
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Taizhou, Zhejing, China, 317000
- Taizhou Hospital of Zhejiang Province
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Kontakt:
- Wenjun Zhao, M.D., Ph.D.
- Telefonnummer: +86-139-5856-1810
- E-Mail: zhaowj@enzemed.com
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Wenzhou, Zhejing, China, 325000
- The First Affiliated Hospital of Wenzhou Medical University
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Kontakt:
- Jingyong Huang, M.D.
- Telefonnummer: +8613616631391
- E-Mail: 43737136@qq.com
-
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Nein
Beschreibung
Inclusion Criteria:
- Male or female, aged 18 years or older at the time of signing informed consent
- Clinical diagnosis of type 2 diabetes mellitus with a diabetic foot ulcer and chronic limb-threatening ischemia classified as Rutherford category 5. The target limb must have an ischemic foot ulcer corresponding to WIfI wound grade 1 or 2. After at least 2 weeks of optimal standard wound care, including debridement, offloading, and infection control as clinically indicated, the ulcer must show no clear healing tendency, defined as a reduction in area of less than 30%, and infrapopliteal revascularization must be considered necessary to improve perfusion and promote wound healing.
- Color duplex ultrasonography, computed tomography angiography (CTA), or digital subtraction angiography (DSA) demonstrates at least 70% stenosis or occlusion in one or more infrapopliteal arteries, the anterior tibial, posterior tibial, or peroneal artery, and the investigator considers this disease to be the principal cause of ischemia in the target limb.
- No severe stenosis in the supra-popliteal inflow arteries, including the iliac, femoral, and popliteal arteries, defined as less than 70% stenosis; alternatively, any severe inflow stenosis can be treated during the index procedure. The infrapopliteal lesion or lesions must remain the principal revascularization target.
- Objective evidence of severe limb ischemia meeting at least one of the following criteria: ankle-brachial index (ABI) ≤0.50; ankle systolic pressure measured at the dorsalis pedis or posterior tibial artery ≤70 mmHg; or transcutaneous oxygen pressure (TcPO₂) <30 mmHg. If ABI is >1.30 or otherwise considered unreliable because of arterial incompressibility, eligibility will be determined using toe-brachial index (TBI), toe pressure where available, and/or TcPO₂.
- Willing and able to comply with study procedures and complete all scheduled follow-up assessments.
- Provides written informed consent voluntarily before any study-specific procedure.
Exclusion Criteria:
- Unable or unwilling to undergo lower-extremity arterial revascularization.
- WIfI foot-infection grade 3, including systemic infection or severe local infection requiring urgent surgical debridement. A potential participant may be reassessed after adequate antimicrobial and surgical management if the infection has improved to WIfI infection grade 1 or 2, systemic infection has resolved, and relevant infection indicators have returned to an acceptable range.
- Gangrene or tissue destruction of the target limb for which above-ankle major amputation is considered immediately necessary or unavoidable.
- Any contraindication to seltoplasmid injection according to the current prescribing information.
- Acute myocardial infarction, stroke, intracranial hemorrhage, or unstable angina within 3 months before randomization.
- Acute limb ischemia or acute exacerbation of chronic limb ischemia within 3 months before randomization.
- New York Heart Association class IV heart failure.
- Severe hepatic impairment, including decompensated cirrhosis, jaundice, ascites, or variceal bleeding.
- Severe renal impairment, defined as serum creatinine >2.5 times the upper limit of normal or estimated glomerular filtration rate <30 mL/min/1.73 m², or current dialysis.
- Coagulation disorder, defined as platelet count <75 × 10⁹/L or international normalized ratio >1.5 that cannot be corrected.
- Hemoglobin <80 g/L or white blood cell count <3.0 × 10⁹/L.
- Alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal.
- Poorly controlled diabetes mellitus, defined as glycated hemoglobin >10%.
- Active malignant tumor or a history of malignant tumor within 5 years before enrollment. Any broader malignancy-related contraindication in the current seltoplasmid prescribing information will take precedence.
- Pregnant or breastfeeding woman, or woman of childbearing potential unwilling to use effective contraception during the protocol-defined period. Pregnancy testing and contraceptive requirements will follow the protocol and current prescribing information.
- Life expectancy <12 months or, in the investigator's judgment, inability to complete follow-up.
- Participation in another interventional clinical study within 30 days before enrollment.
- Positive human immunodeficiency virus antibody; positive hepatitis C virus antibody; or positive hepatitis B surface antigen together with detectable peripheral-blood hepatitis B virus DNA when, in the investigator's judgment, active chronic hepatitis B may increase participant risk.
- Current treatment with immunosuppressive therapy, radiotherapy, or chemotherapy.
- Any serious comorbidity that may interfere with assessment of study outcomes, or any psychological or social circumstance that may materially prevent optimal participation in the study, in the investigator's judgment.
- Any other condition that, in the investigator's judgment and with the reason documented, makes participation inappropriate or exposes the participant to unacceptable risk.
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Single
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Experimental: Seltoplasmid Plus Revascularization
Following completion of the index lower-extremity revascularization procedure, participants will receive Seltoplasmid Injection in addition to protocol-defined standard care.
Seltoplasmid will be administered at a total dose of 8 mg by intramuscular injection at 32 sites in the affected lower leg on Day 0, Day 14 (±3 days), and Day 28 (±3 days), provided that the prespecified safety conditions are met.
Standard care includes wound care, offloading, glycemic control, treatment of infection, antiplatelet therapy, lipid-lowering therapy, and other clinically indicated treatment.
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All participants will undergo index lower-extremity revascularization before randomization, with infrapopliteal arterial disease as the principal treatment target.
The revascularization strategy and technique will be selected by the treating vascular specialist according to the participant's vascular anatomy, clinical condition, and protocol-defined procedural standards.
After completion of the procedure and confirmation of postoperative eligibility and safety, participants will be randomized to one of the two study arms.
Seltoplasmid will be administered at a total dose of 8 mg per treatment session by intramuscular injection at 32 prespecified sites in the affected lower leg.
Treatment will be administered on Day 0 after revascularization, Day 14 (±3 days), and Day 28 (±3 days), provided that the prespecified dosing and safety conditions are met.
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Aktiver Komparator: Revascularization
Following completion of the index lower-extremity revascularization procedure, participants will receive protocol-defined standard care without Seltoplasmid Injection or placebo injections.
Standard care includes wound care, offloading, glycemic control, treatment of infection, antiplatelet therapy, lipid-lowering therapy, and other clinically indicated treatment.
Participants will be followed according to the same visit schedule and outcome-assessment procedures as those in the experimental group.
|
All participants will undergo index lower-extremity revascularization before randomization, with infrapopliteal arterial disease as the principal treatment target.
The revascularization strategy and technique will be selected by the treating vascular specialist according to the participant's vascular anatomy, clinical condition, and protocol-defined procedural standards.
After completion of the procedure and confirmation of postoperative eligibility and safety, participants will be randomized to one of the two study arms.
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Time to First Clinically Driven MALE or All-Cause Death
Zeitfenster: From randomization through Day 360 (±14 days)
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Time from randomization to the first occurrence of a clinically driven major adverse limb event (MALE) or all-cause death, whichever occurs first.
MALE is defined as target-limb major amputation (amputation at or above the ankle) or clinically driven target-limb revascularization.
Participants without an event will be censored at the date of their last available assessment.
All suspected endpoint events will be adjudicated by an independent clinical event committee blinded to treatment assignment.
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From randomization through Day 360 (±14 days)
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
Zeitfenster: From randomization through Day 360 (±14 days)
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Number and percentage of participants with treatment-emergent adverse events, serious adverse events, adverse reactions, adverse events leading to treatment discontinuation, and deaths.
Events will be coded using MedDRA and graded according to the protocol-specified version of the Common Terminology Criteria for Adverse Events.
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From randomization through Day 360 (±14 days)
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Incidence of Clinically Driven Target-Lesion Revascularization
Zeitfenster: From randomization through Day 360 (±14 days)
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Cumulative incidence of clinically driven target-lesion revascularization (CD-TLR) in the target limb.
CD-TLR is defined as repeat endovascular or surgical treatment of the index target lesion prompted by recurrent or worsening clinical symptoms, wound deterioration, or objective evidence of impaired perfusion.
Death and target-limb major amputation will be treated as competing events.
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From randomization through Day 360 (±14 days)
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Amputation-Free Survival
Zeitfenster: From randomization through Day 360 (±14 days)
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Time from randomization to the first occurrence of target-limb major amputation or all-cause death, whichever occurs first.
Major amputation is defined as amputation at or above the ankle.
Participants without an event will be censored at the date of their last available assessment.
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From randomization through Day 360 (±14 days)
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Proportion of Participants With Confirmed Complete Ulcer Healing
Zeitfenster: From randomization through Day 360 (±14 days)
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Proportion of participants with complete healing of the target ulcer, defined as complete epithelialization without drainage or the need for a dressing, confirmed at two consecutive scheduled assessments.
Healing assessments will be supported by standardized wound measurement and photography.
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From randomization through Day 360 (±14 days)
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Time to Confirmed Complete Ulcer Healing
Zeitfenster: Baseline and scheduled assessments through Day 360 (±14 days)
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Change from baseline in target-limb rest pain measured using an 11-point numerical rating scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain.
A decrease from baseline indicates improvement.
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Baseline and scheduled assessments through Day 360 (±14 days)
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Change From Baseline in Target-Limb Rest Pain Score
Zeitfenster: Baseline and scheduled assessments through Day 360 (±14 days)
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Change from baseline in target-limb rest pain measured using an 11-point numerical rating scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain.
A decrease from baseline indicates improvement.
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Baseline and scheduled assessments through Day 360 (±14 days)
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Change From Baseline in Target-Limb Transcutaneous Oxygen Pressure
Zeitfenster: Baseline and scheduled assessments through Day 360 (±14 days)
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Transcutaneous oxygen pressure (TcPO₂) will be measured in mmHg under standardized conditions at a prespecified, reproducible site near the target wound.
The same device, probe location, participant position, and measurement conditions should be used whenever possible.
An increase from baseline indicates improved tissue oxygenation and microcirculatory perfusion.
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Baseline and scheduled assessments through Day 360 (±14 days)
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Change From Baseline in Target-Limb Ankle-Brachial Index
Zeitfenster: Baseline and scheduled assessments through Day 360 (±14 days)
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Change from baseline in the ankle-brachial index (ABI) of the target limb at each scheduled assessment.
ABI will be calculated as the higher target-ankle systolic pressure divided by the higher brachial systolic pressure, using a standardized measurement procedure.
An increase from baseline generally indicates improved limb perfusion.
ABI will be interpreted cautiously in participants with noncompressible arteries.
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Baseline and scheduled assessments through Day 360 (±14 days)
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Incidence of Major Adverse Cardiovascular Events
Zeitfenster: From randomization through Day 360 (±14 days)
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Cumulative incidence of the first major adverse cardiovascular event (MACE), defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
Only the first qualifying event will be counted in the time-to-first-event analysis.
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From randomization through Day 360 (±14 days)
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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
Allgemeine Veröffentlichungen
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Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Geschätzt)
20. Oktober 2026
Primärer Abschluss (Geschätzt)
1. Oktober 2028
Studienabschluss (Geschätzt)
31. Dezember 2029
Studienanmeldedaten
Zuerst eingereicht
11. September 2026
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
17. September 2026
Zuerst gepostet (Tatsächlich)
18. September 2026
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
18. September 2026
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
17. September 2026
Zuletzt verifiziert
1. September 2026
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des endokrinen Systems
- Gefäßerkrankungen
- Herz-Kreislauf-Erkrankungen
- Pathologische Prozesse
- Chronische Erkrankung
- Krankheitsattribute
- Diabetes Mellitus
- Diabetische Angiopathien
- Diabetes-Komplikationen
- Hautkrankheiten
- Hautgeschwür
- Beingeschwür
- Diabetische Neuropathien
- Atherosklerose
- Arteriosklerose
- Arterielle Verschlusskrankheiten
- Periphere Gefäßerkrankungen
- Ischämie
- Fußgeschwür
- Periphere arterielle Verschlusskrankheit
- Pathologische Zustände, Anzeichen und Symptome
- Haut- und Bindegewebserkrankungen
- Chronische, die Gliedmaßen bedrohende Ischämie
- Diabetischer Fuß
Andere Studien-ID-Nummern
- ky2026-432
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Beschreibung des IPD-Plans
Individual participant data will not be made publicly available because the informed consent does not authorize unrestricted secondary use or public sharing of participant-level data.
The dataset may contain sensitive clinical information, vascular imaging, wound photographs, and gene-therapy safety data.
Aggregate and de-identified study results will be reported through trial registration, scientific publications, and other applicable regulatory channels.
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