Adaptive Platform Trial for Pain Management in Sickle Cell Vaso-Occlusive Crisis

Inclusion Criteria: * Adult patients (age ≥18 years) * Diagnosed with major sickle cell syndrome (SS homozygous, SC or Sβ° or Sβ+ thalassemia compound heterozygous) * Hospitalized and presenting with a vaso-occlusive crisis (VOC), defined as acute pain or tenderness affecting at least one part of the body, including the limbs, ribs, sternum, head (skull), spine, and/or pelvis, not attributable to other causes * Requiring intravenous morphine or its derivatives * Informed consent obtained from the patient (or from a trusted support person, family member, or relative), or emergency inclusion procedure in cases where the patient is unable to consent and no trusted support person, family member, or relative is available Exclusion Criteria: * Refusal to participate * Pregnant or breastfeeding patient * Administration of one of the interventional group treatments within 4 hours prior to inclusion * Intravenous morphine treatment for more than 24 hours * Patient already included in the study within the previous 3 months * Patient receiving long-term opioid therapy * Not affiliated with a social security scheme, or patient under State Medical Aid (AME) * Patient under legal protection measures (guardianship / family authorization with representation mandate / future protection mandate) or under supervised guardianship (curatelle) * Patient deprived of liberty * Participation in another clinical trial involving a drug * Participation in the PAMAVOC trial within the previous 3 months * Contraindication to standard VOC treatment: * Hypersensitivity to opioids * Opioid-induced hyperalgesia, defined by increased pain on nociceptive testing, topographic extension, or the onset of allodynia with increasing opioid doses * Renal impairment, defined as creatinine clearance ≤30 mL/minute * Hepatocellular impairment, defined as prothrombin time \<40% * Impaired consciousness, defined as a Glasgow Coma Scale score ≤13/15 Exclusion from a Specific Intervention (randomization possible to other study arms): * Hypersensitivity to the active substance or to any of the excipients * Respective contraindications to nefopam, tramadol, ketoprofen, and ketamine, as described in their respective Summaries of Product Characteristics (SmPC)