Evaluation of the Efficacy of Iloprost in the Management of Vaso-occlusive Crises in Adult Patients With Sickle Cell Disease

Официальное название

Evaluation of the Efficacy of Iloprost in the Management of Vaso-occlusive Crises in Adult Patients With Sickle Cell Disease: Multicenter, Randomized, Double-blind, Placebo-controlled Study

Обзор

Sickle cell disease is a severe monogenic genetic disorder caused by an autosomal recessive mutation of the β-globin gene, leading to production of abnormal hemoglobin (HbS). It primarily affects individuals from Africa or the French overseas territories. In France, approximately 26,000 patients are affected. Improved care has significantly increased life expectancy. Vaso-occlusive crises (VOC) are the main clinical complication. They result from polymerization of HbS, deforming red blood cells and causing capillary occlusion, tissue hypoxia, intense bone pain, and frequent hospitalizations. In France in 2015, 25,150 hospitalizations were recorded, 61% of which were for VOC. Iloprost is a prostacyclin (PGI2) analogue with vasodilatory, anti-platelet, anti-inflammatory, and antioxidant properties. It is used to treat severe limb ischemia and Raynaud's phenomenon, administered by IV infusion for 5 to 28 days. It is well tolerated and has shown efficacy for bone pain related to bone marrow edema. Its rapid and sustained action makes it an interesting candidate for VOC, which are comparable to ischemic-origin pain. To date, only one reported case of iloprost use for a VOC exists, showing rapid and lasting improvement. This randomized, multicenter, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy of iloprost in patients hospitalized for VOC, with the objective of reducing pain and opioid consumption. This comprehensive approach could significantly improve VOC management.

Вмешательства

• Препарат Iloprost
  1 ampoule IV over 6 h daily for 5 days diluted in 250 mL G5%
• Препарат Placebo
  250 mL G5% IV over 6 h daily for 5 days

Первичные конечные точки

• Opioid consumption [Срок оценки: 28 days following randomization]

Вторичные конечные точки (12)

• Mean pain [Срок оценки: 28 days following randomization]
• Length of hospital [Срок оценки: 28 days following randomization]
• Acute chest syndrome during hospitalization [Срок оценки: 28 days following randomization]
• Number of priapism episodes during hospitalization [Срок оценки: 28 days following randomization]
• hemoglobin level [Срок оценки: 5 days following randomization]
• reticulocyte count [Срок оценки: 5 days following randomization]
• lactate dehydrogenase activity [Срок оценки: 5 days following randomization]
• leukocyte count [Срок оценки: 5 days following randomization]
• C-reactive protein [Срок оценки: 5 days following randomization]
• thrombin generation test [Срок оценки: 5 days following randomization]
• D-dimers [Срок оценки: 5 days following randomization]
• prothrombin fragments 1+2 [Срок оценки: 5 days following randomization]

Критерии участия

Критерии включения

Patients with major sickle cell syndrome (all genotypes). 2. Age ≥18 years 3. Require hospitalization and IV opioids for VOC treatment. 4. Admitted less than 36 hours before inclusion; H0 = hospital admission time. 5. Have read and signed informed consent. 6. For women:

• Of childbearing potential (defined by the CTCG as a fertile woman, after menarche and until menopause, except in cases of permanent sterility, including hysterectomy, bilateral salpingectomy, or bilateral oophorectomy);

• Using a highly effective method of contraception according to CTCG recommendations (combined hormonal contraception \[containing estrogens and progestogens\] associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, sexual abstinence) for at least 4 weeks prior to inclusion and throughout the entire duration of systemic exposure to the study treatment. AND
• Having a negative urine pregnancy test at inclusion;
• Postmenopausal: Menopause, according to CTCG recommendations, is defined as the absence of menstruation for 12 months without any other medical cause. Elevated follicle-stimulating hormone (FSH) levels in the postmenopausal interval can be used to confirm postmenopausal status in women who are not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

7\. Affiliated with a social security system

Критерии исключения

• Patients with a contraindication to iloprost (ILOPROST ZENTIVA 100 micrograms/mL, solution for dilution for infusion):

• pregnancy, breastfeeding
• Hypersensitivity to the active substance or to any of the excipients.
• Conditions where the risk of bleeding may be increased due to the effects of iloprost on platelets (e.g., active peptic ulcer, trauma, intracranial hemorrhage).
• severe coronary disease
• recent MI <6 months
• heart failure NYHA II-IV
• severe arrhythmias
• suspicion of pulmonary congestion
• Active smoking
• Patient presenting with hepatic impairment or renal impairment requiring dialysis
• Patient presenting with a contraindication to 5% glucose (Glucose 5%

FRESENIUS KABI France solution for infusion):

• Hypersensitivity to corn
• Uncontrolled hyperglycemia,
• Decompensated diabetes,
• Other known glucose intolerances (e.g. situations of metabolic stress, acute shock states, collapse),
• Hyperosmolar coma,
• Hyperlactatemia,
• Metabolic acidosis,
• Fluid overload. The administration of high volumes may in particular result, due to fluid overload, in the following contraindications:
• Hyperhydration
• Acute heart failure
• Pulmonary edema
• Hypersensitivity to 5% glucose
• Severe malnutrition
• Thiamine deficiency in chronic alcoholic patients
• Patient presenting with arterial hypotension
• Patient having experienced a cerebrovascular event within the last 3 months
• History of documented opioid dependence
• Individuals deprived of liberty or under legal protection.
• Patient included in PROSTASICKLE within last 90 days.
• Participation in another drug trial within previous month.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• CHU de Rouen — Rouen

Идентификаторы

NCT: NCT07498309 · 2020/0421/HP · 2025-522005-38-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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