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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Sickle Cell Disease; Vaso-Occlusive Crises
• Intervention / Treatment: Drug: Iloprost; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mylene HERVET; Email: mylene.hervet@chu-rouen.fr
• Study Contact Backup: Name: Maximilien GRALL; Phone Number: +332 32 88 58 28; Email: Maximilien.Grall@chu-rouen.fr

Study Locations

• France
  • Rouen, France
    • CHU de Rouen
    • Contact: Dr. GRALL; Phone Number: +332 32 88 58 28; Email: maximilien.grall@chu-rouen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

   1. pregnancy, breastfeeding
   2. Hypersensitivity to the active substance or to any of the excipients.
   3. 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).
   4. severe coronary disease
   5. recent MI <6 months
   6. heart failure NYHA II-IV
   7. severe arrhythmias
   8. suspicion of pulmonary congestion
2. Active smoking
3. Patient presenting with hepatic impairment or renal impairment requiring dialysis

4. Patient presenting with a contraindication to 5% glucose (Glucose 5%

   FRESENIUS KABI France solution for infusion):

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 250 mL G5% IV over 6 h daily for 5 days
Experimental: Iloprost	Drug: Iloprost; 1 ampoule IV over 6 h daily for 5 days diluted in 250 mL G5%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid consumption	Mean opioid consumption in morphine equivalent mg/day over the 28 days following randomization	28 days following randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean pain	Mean pain according to the VAS (Visual Analog Scale) over the first 28 days. The VAS used in this study will be a scale from 0 to 10, with ratings ranging from "no pain" (0) to "the worst pain" (10). If the patient has multiple painful areas, the worst pain should be reported.	28 days following randomization
Length of hospital	Length of hospital stay capped at 28 days	28 days following randomization
Acute chest syndrome during hospitalization		28 days following randomization
Number of priapism episodes during hospitalization		28 days following randomization
hemoglobin level	Change in hemoglobin level (in g/dL) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
reticulocyte count	Change in reticulocyte count (in giga/L) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
lactate dehydrogenase activity	Change in lactate dehydrogenase activity (in IU/L) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
leukocyte count	Change in leukocyte count (in giga/L) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
C-reactive protein	Change in serum C-reactive protein concentration (in mg/L) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
thrombin generation test	Change in thrombin generation test result via thrombin peak height between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
D-dimers	Change in D-dimers (μg/L) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
prothrombin fragments 1+2	Change in serum concentration of prothrombin fragments 1+2 (nmol/L) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
thrombomodulin concentration	Change in serum thrombomodulin concentration (ng/mL) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
erythrocyte microvesicles	Change in blood concentration of erythrocyte microvesicles (vesicles/μL) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
S-endothelin concentration	Change in serum S-endothelin concentration (pg/mL) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
E-selectin concentration	Change in serum E-selectin concentration (ng/mL) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
P-selectin concentration	Change in serum P-selectin concentration (ng/mL) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
VCAM-1 concentration	Change in serum VCAM-1 concentration (ng/mL) between baseline (day of randomization) and the 5-day assessment, or at hospital discharge if this occurs before 5 days	5 days following randomization
Number of vaso-occlusive crises	occurring within 90 days after randomization, excluding the initial vaso-occlusive crisis	90 days following randomization
Total cost of management	Total cost of management including prescription costs (notably iloprost) and costs associated with hospitalizations (from the health insurance perspective)	90 days following randomization
Time interval between randomization and last opioid use	Time interval between randomization and last opioid use at 28 days	28 days following randomization
Duration of priapism episodes during hospitalization		28 days following randomization

Collaborators and Investigators

• Sponsor: University Hospital, Rouen

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: March 16, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Vaso-Occlusive Crises; Fatty Acids; Lipids; Biological Factors; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Autacoids; Inflammation Mediators; Iloprost
• Other Study ID Numbers: 2020/0421/HP; 2025-522005-38-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No