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APAC (antiplatelet, anticoagulant) antithrombotic treatment for limb-threatening impairment of blood flow (HEALING-study)
EU CTIS ID: 2025-522390-11-00
What this study is testing
Part A: To evaluate safety and tolerability of i.v. APAC for single infusion and weekly dosing.; Part B: To establish the safety of the selected dose(s) and dosing frequency of periprocedural i.a. and weekly i.v. APAC administration in patients undergoing endovascular revascularization.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Parts A1, B1, and B2: 1. Males aged 45-85 years and postmenopausal females (i.e. no menstrual periods for 12 months without an alternative medical cause) up to 85 years.
- Part A2: 2. Diagnosed with: a. PAOD classification Fontaine stage IIa and IIb; b. not prescheduled for endovascular revascularization within 90 days of first APAC administration.
- Part A2: 3. CTA/MRA/DSA with contrast agent performed within 3 months prior to study enrolment.
- Part A2: 4. Moderate to severe arterial disease, ABI < 0.7
- Part A2: 5. Patients should be capable of performing evaluable treadmill exercise test.
- Part A2: 6. Patients should be treated with antithrombotic medication either acetylsalicylic acid (up to 100 mg QD) or clopidogrel (up to 75 mg QD) for at least the preceding five days before the first APAC administration.
You likely can't join if
- 1. Any ischemic lesions of the heel and midfoot and lesions (wounds or gangrene) invading bones, joints, or tendons at metatarsophalangeal joints or more proximal sites.
- 10. Patients with clinically significant acute infection, as judged by the investigator.
- 11. Use of non-steroidal anti-inflammatory medications within 2 weeks prior to the first dose of APAC or during the treatment period. If medication for pain is required, paracetamol or tramadol (e.g. an opioid patch) may be used.
- 12. Use of selective serotonin reuptake inhibitor (SSRI) medication within 2 weeks prior to the first dose of APAC or during the treatment period.
- 13. Peroral use of glycosaminoglycans or omega 3 or related products within 28 days before IMP treatment.
- 14. Major surgery, major trauma or any endovascular intervention within the past 90 days or organ biopsy prior to the screening visit or scheduled for such an intervention during the study.
See the full eligibility criteria
Who can join
- Parts A1, B1, and B2: 1. Males aged 45-85 years and postmenopausal females (i.e. no menstrual periods for 12 months without an alternative medical cause) up to 85 years.
- Part A2: 2. Diagnosed with: a. PAOD classification Fontaine stage IIa and IIb; b. not prescheduled for endovascular revascularization within 90 days of first APAC administration.
- Part A2: 3. CTA/MRA/DSA with contrast agent performed within 3 months prior to study enrolment.
- Part A2: 4. Moderate to severe arterial disease, ABI < 0.7
- Part A2: 5. Patients should be capable of performing evaluable treadmill exercise test.
- Part A2: 6. Patients should be treated with antithrombotic medication either acetylsalicylic acid (up to 100 mg QD) or clopidogrel (up to 75 mg QD) for at least the preceding five days before the first APAC administration.
- Part A2: 7. Adequate lipid lowering therapy, as evaluated by the investigator.
- Part A2: 8. Capability and willingness to provide valid, voluntary written informed consent for the study.
- Part A2: 9. Males must be willing to use a condom and their female partners of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must be willing to use highly effective contraception while on study treatment. Highly effective methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); Intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; and sexual abstinence.
- Part A2: 10. Males must refrain from sperm donation while on study treatment.
- Parts A1, B1, and B2: 2. Diagnosed with: a. PAOD classification Fontaine stage III or IV; b. the total length of the treatment-targeted arterial segment ≥ 5 cm below the knee lesion(s) based on contrast-enhanced computed tomography angiography (CTA)/magnetic resonance angiography (MRA)/digital subtraction angiography (DSA) (Part B1 and B2); c. superficial forefoot wounds without overt infection and bone invasion (WIfI 0-1 and 2 limited to digits and WIfI infection 0-1)Mills et al. 2014 allowed; d.undergoing endovascular intervention. (In Part A1, if prescheduled endovascular intervention would take place before the D8 study visit, patient is not to be enrolled.)
- Parts A1, B1, and B2: 3. CTA/MRA/DSA with contrast agent performed within 3 months prior to study enrolment as part of diagnostics of PAOD, with results available in the patient’s medical records.
- Parts A1, B1, and B2: 4. Patients should be treated with antithrombotic medication either acetylsalicylic acid (up to 100 mg QD) or clopidogrel (up to 75 mg QD) for at least the preceding five days before the first APAC administration.
- Parts A1, B1, and B2: 5. Adequate lipid lowering therapy, as evaluated by the investigator.
- Parts A1, B1, and B2: 6. Capability and willingness to provide valid, voluntary written informed consent for the study.
- Parts A1, B1, and B2: 7. Males must be willing to use a condom and their female partners of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must be willing to use highly effective contraception while on study treatment. Highly effective methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); Intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; and sexual abstinence.
- Parts A1, B1, and B2: 8. Males must refrain from sperm donation while on study treatment.
- Part A2: 1. Males aged 45-85 years and postmenopausal females (i.e. no menstrual periods for 12 months without an alternative medical cause) up to 85 years.
What rules you out
- 1. Any ischemic lesions of the heel and midfoot and lesions (wounds or gangrene) invading bones, joints, or tendons at metatarsophalangeal joints or more proximal sites.
- 10. Patients with clinically significant acute infection, as judged by the investigator.
- 11. Use of non-steroidal anti-inflammatory medications within 2 weeks prior to the first dose of APAC or during the treatment period. If medication for pain is required, paracetamol or tramadol (e.g. an opioid patch) may be used.
- 12. Use of selective serotonin reuptake inhibitor (SSRI) medication within 2 weeks prior to the first dose of APAC or during the treatment period.
- 13. Peroral use of glycosaminoglycans or omega 3 or related products within 28 days before IMP treatment.
- 14. Major surgery, major trauma or any endovascular intervention within the past 90 days or organ biopsy prior to the screening visit or scheduled for such an intervention during the study.
- 15. Uncontrolled arterial hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg).
- 16. Blood hemoglobin concentration <120 g/L or > 170 g/L (men) and <110 g/L or >160 g/L (women) at screening.
- 17. Blood platelet count <150 x 109/L or > 450 x109/L and/or leukocyte count in the lower reference range or not above >12 x 109/L.
- 18. Clinically significantly prolonged plasma PT (> 1.2-fold) or a value of less than 50% (when normal reference range is 70-130%).
- 19. APTT above the upper limit of the reference range.
- 2. Acute limb-threatening ischemia (e.g., thromboembolic disease).
- 20. Patients with a medical history of heparin-induced thrombocytopenia.
- 21. Patients with known significant liver disease, incl. an alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) level > 2.5 x the upper limit of normal (ULN) at screening.
- 22. A diagnosis of severe chronic kidney disease, defined as having an eGFR category 4 or 5 (eGFR < 30 mL/min/1.73 m2 as per calculation of Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) or albuminuria stage A3 (uACR >300 mg/g).
- 23. Patients with an active malignancy, or who have received treatment for any malignancy including bone marrow transplantation within 5 years before the screening visit, except for localized basal cell or squamous cell skin cancer that has been cured at least 90 days before screening.
- 24. Previous treatment with APAC.
- 25. Patients with known allergy or hypersensitivity to heparin, or heparin products, APAC, and/or antiplatelet agents (e.g., aspirin or clopidogrel), and protamine sulphate, the reversal agent for APAC.
- 26. Participation in an investigational drug or device study within 90 days prior to screening.
- 27. Patients who have ever received treatment with a gene therapy.
- 28. Patients with known antiphospholipid antibody syndrome or other known significant thrombophilia (homozygosity for FV Leiden or FIIG20210A mutation, or phospholipid antibody syndrome, deficiency of antithrombin, protein C or protein S or combined thrombophilias).
- 29. Any concomitant disease or condition or treatment that could interfere with, or the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the patient in this study as judged by the investigator.
- 3. Medical history of, or an existing aneurysm.
- 30. Patients with severe comorbidities and limited life expectancy as judged by the investigator.
- 31. Patients unable or unwilling to comply with the protocol or to cooperate fully with the investigator or site personnel.
- 32. Patients with current and/or history of drug abuse (defined as illicit drug use) or alcohol abuse (defined as daily consumption of more than 23-24 and 12-16 alcoholic drinks per week in males and femals, respectively
- 4. Endovascular revascularization intervention is done from the contralateral side using cross-over access (Part B1 and B2).
- 5. Medical history of, or condition known to be associated with impaired hemostasis, i.e., increased intracranial bleeding risk e.g., previous history of intracranial hemorrhage, subarachnoidal bleeding, hemorrhagic stroke, thrombotic or thromboembolic stroke, gastrointestinal bleeding within 6 months of enrolment, or retroperitoneal bleeding any time, or any inherited or acquired bleeding disorder, i.e., von Willebrand disease or hemophilia or other relevant diagnosis causing impaired hemostasis.
- 6. Current use of therapeutic dose of anticoagulation (warfarin, apixaban, rivaroxaban, dabigatran, edoxaban, fondaparinux, or any heparin derivative) for any medical reason. (Use of dual pathway inhibition [= acetylsalicylic acid 100 mg + rivaroxabahn 2.5 mg x 2] is not a contraindication, but will be temporarily halted for the day of intervention and day of repeating dosing.)
- 7. Patients treated with combined antiplatelet agents: aspirin + P2Y12 antagonist (clopidogrel, ticagrelor, prasugrel).
- 8. Diagnosis of autoimmune diabetes mellitus (Type 1 diabetes, or latent autoimmune diabetes in adults [LADA]) vasculitis, rheumatoid arthritis, inflammatory bowel diseases, or other general autoimmune diseases.
- 9. Body mass index > 35 kg/m2.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.