[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100656599":3},{"organization":4,"outcomesModule":7,"designInfo":52,"detailedDescription":51,"studyPopulation":51,"armGroups":58,"interventions":93,"overallOfficials":124,"centralContacts":129,"locations":51,"responsibleParty":139,"collaborators":51,"id":141,"slug":142,"hasResults":143,"nctId":144,"briefTitle":145,"officialTitle":146,"acronym":147,"eligibilityCriteria":148,"healthyVolunteers":143,"sex":149,"minAge":150,"maxAge":51,"enrollmentInfo":151,"targetDuration":51,"studyType":154,"phases":155,"briefSummary":157,"conditions":158,"keywords":161,"overallStatus":167,"whyStopped":51,"lastUpdateSubmitDate":168,"lastUpdatePostDateStruct":169,"startDateStruct":172,"completionDateStruct":174,"leadSponsor":176,"locationsCount":51},{"fullName":5,"class":6},"Assistance Publique - Hôpitaux de Paris","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":51},[9],{"measure":10,"description":11,"timeFrame":12},"Time to resolution of vaso-occlusive crisis (VOC)","Time to resolution of vaso-occlusive crisis is defined as the time from randomization to discontinuation of intravenous opioid therapy, measured in hours.","Up to 14 days after randomization.",[14,18,22,25,29,32,36,40,43,47],{"measure":15,"description":16,"timeFrame":17},"Intravenous Morphine Consumption","Cumulative dose (mg) and mean daily dose (mg\u002Fday) of intravenous morphine.","From admission to discharge, assessed up to 14 dayss)",{"measure":19,"description":20,"timeFrame":21},"Transfusion Requirements","Number of red blood cell units transfused.","From admission to discharge, assessed up to 14 days",{"measure":23,"description":24,"timeFrame":21},"Intensive Care Unit Admission","Admission to intensive care unit during hospitalization.",{"measure":26,"description":27,"timeFrame":28},"Morphine-Related Adverse Effects","Constipation, sedation (impaired consciousness requiring opioid discontinuation or naloxone administration), vomiting, and secondary acute chest syndrome (new pulmonary infiltrate associated with a clinical sign such as fever, or a respiratory sign such as chest pain or dyspnea).","Within 3 months (+\u002F- 15 days)",{"measure":30,"description":31,"timeFrame":21},"Length of Hospital Stay","Duration of hospitalization, measured in days",{"measure":33,"description":34,"timeFrame":35},"Hyperalgic Vaso-Occlusive Crisis","Uncontrolled pain requiring morphine titration \\>1 mg\u002Fkg or total intravenous morphine consumption \\>2 mg\u002Fkg\u002F24h.","from randomization to discontinuation of intravenous opioid therapy Up to 14 days",{"measure":37,"description":38,"timeFrame":39},"Refractory Vaso-Occlusive Crisis","Visual analog scale (VAS) score \\>7\u002F10 after administration of study treatments and a new morphine titration (1 mg\u002Fkg).","From randomization to discontinuation of intravenous opioid therapy Up to 14 days",{"measure":41,"description":42,"timeFrame":28},"Adverse Effects of Investigational Medicinal Products","Including nefopam (seizure); NSAIDs (acute kidney injury, KDIGO stage \\>0; gastrointestinal or other bleeding); tramadol (seizure, liver function abnormalities, impaired consciousness with GCS \\\u003C14\u002F15); ketamine (liver function abnormalities, hallucinations, impaired consciousness with GCS \\\u003C14\u002F15, venous access complications).",{"measure":44,"description":45,"timeFrame":46},"In-Hospital Mortality","Death occurring during hospitalization.","Duration of hospital stay, assessed up to 14 days",{"measure":48,"description":49,"timeFrame":50},"Unplanned Readmission","Unplanned hospital readmission within 3 months following the index hospitalization.","Within 3 months (+\u002F- 15 days) after discharge",null,{"allocation":53,"interventionModel":54,"interventionModelDescription":51,"primaryPurpose":55,"observationalModel":51,"timePerspective":51,"maskingInfo":56},"RANDOMIZED","PARALLEL","TREATMENT",{"masking":57,"maskingDescription":51,"whoMasked":51},"NONE",[59,64,69,73,77,81,85,89],{"label":60,"type":61,"description":51,"interventionNames":62},"Group 01 Control : Paracetamol + Morphine","ACTIVE_COMPARATOR",[63],"Drug: Group 01 Control: Paracetamol + Morphine",{"label":65,"type":66,"description":51,"interventionNames":67},"group 02 : Paracetamol + Morphine + Ketamine","EXPERIMENTAL",[68],"Drug: Group 02 Paracetamol + Morphine + Ketamine",{"label":70,"type":66,"description":51,"interventionNames":71},"Group 03 : Paracetamol + Morphine + Nefopam",[72],"Drug: Group 03 : Paracetamol + Morphine + Nefopam",{"label":74,"type":66,"description":51,"interventionNames":75},"Group 04 : Paracetamol + Morphine + Nefopam + Ketamine",[76],"Drug: Group 04 : Paracetamol + Morphine + Nefopam + Ketamine",{"label":78,"type":66,"description":51,"interventionNames":79},"Group 05 : Paracetamol + Morphine + Tramadol",[80],"Drug: Goup 05 : Paracetamol + Morphine + Tramadol",{"label":82,"type":66,"description":51,"interventionNames":83},"Group 06 : Paracetamol + Morphine + Tramadol + Ketamine",[84],"Drug: Group 6 : Paracetamol + Morphine + Tramadol + Ketamine",{"label":86,"type":66,"description":51,"interventionNames":87},"Group 07 : Paracetamol + Morphine + Ketoprofen",[88],"Drug: Group 7 : Paracetamol + Morphine + Ketoprofen",{"label":90,"type":66,"description":51,"interventionNames":91},"Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine",[92],"Drug: Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine",[94,99,103,106,109,113,117,121],{"type":95,"name":96,"description":97,"armGroupLabels":98,"otherNames":51},"DRUG","Group 02 Paracetamol + Morphine + Ketamine","Participants receive intravenous paracetamol and morphine via PCA. In case of hyperalgic VOC, low-dose ketamine may be added as a co-analgesic, off-label, according to the treating physician's judgment.",[65],{"type":95,"name":100,"description":101,"armGroupLabels":102,"otherNames":51},"Group 01 Control: Paracetamol + Morphine","Participants receive intravenous paracetamol and morphine via patient-controlled analgesia (PCA). In case of hyperalgic VOC, morphine dosage may be increased according to the treating physician's judgment",[60],{"type":95,"name":70,"description":104,"armGroupLabels":105,"otherNames":51},"Participants receive intravenous paracetamol, morphine via PCA, and nefopam. In case of hyperalgic VOC, morphine dosage may be increased according to the treating physician's judgment.",[70],{"type":95,"name":74,"description":107,"armGroupLabels":108,"otherNames":51},"Participants receive intravenous paracetamol, morphine via PCA, and nefopam. In case of hyperalgic VOC, low-dose ketamine may be added as a co-analgesic, off-label, according to the treating physician's judgment.",[74],{"type":95,"name":110,"description":111,"armGroupLabels":112,"otherNames":51},"Goup 05 : Paracetamol + Morphine + Tramadol","Participants receive intravenous paracetamol, morphine via PCA, and tramadol. In case of hyperalgic VOC, morphine dosage may be increased according to the treating physician's judgment.",[78],{"type":95,"name":114,"description":115,"armGroupLabels":116,"otherNames":51},"Group 6 : Paracetamol + Morphine + Tramadol + Ketamine","Participants receive intravenous paracetamol, morphine via PCA, and tramadol. In case of hyperalgic VOC, low-dose ketamine may be added as a co-analgesic, off-label, according to the treating physician's judgment.",[82],{"type":95,"name":118,"description":119,"armGroupLabels":120,"otherNames":51},"Group 7 : Paracetamol + Morphine + Ketoprofen","Participants receive intravenous paracetamol, morphine via PCA, and ketoprofen. In case of hyperalgic VOC, morphine dosage may be increased according to the treating physician's judgment.",[86],{"type":95,"name":90,"description":122,"armGroupLabels":123,"otherNames":51},"Participants receive intravenous paracetamol, morphine via PCA, and ketoprofen. In case of hyperalgic VOC, low-dose ketamine may be added as a co-analgesic, off-label, according to the treating physician's judgment.",[90],[125],{"name":126,"affiliation":127,"role":128},"Ségolène GENDREAU, MD, PhD","Assistance public Hôpitaux de Paris","STUDY_CHAIR",[130,135],{"name":131,"role":132,"phone":133,"phoneExt":51,"email":134},"Samia BALOUL","CONTACT","01 49 81 33 85","samia.baloul@aphp.fr",{"name":136,"role":132,"phone":137,"phoneExt":51,"email":138},"Ségolène GENDREAU","01.45.17.85.06","segolene.gendreau@aphp.fr",{"type":140,"investigatorFullName":51,"investigatorTitle":51,"investigatorAffiliation":51,"oldNameTitle":51,"oldOrganization":51},"SPONSOR","100656599","phase-4-adaptive-platform-trial-for-pain-management-in-sickle-cell-vaso-occlusive-crisis-100656599",false,"NCT07826988","Adaptive Platform Trial for Pain Management in Sickle Cell Vaso-Occlusive Crisis","Adaptive Platform Trial for Pain Management During Vaso-Occlusive Crisis in Adult Patients With Sickle Cell Disease","PAMAVOC","Inclusion Criteria:\n\n* Adult patients (age ≥18 years)\n* Diagnosed with major sickle cell syndrome (SS homozygous, SC or Sβ° or Sβ+ thalassemia compound heterozygous)\n* 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\u002For pelvis, not attributable to other causes\n* Requiring intravenous morphine or its derivatives\n* 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\n\nExclusion Criteria:\n\n* Refusal to participate\n* Pregnant or breastfeeding patient\n* Administration of one of the interventional group treatments within 4 hours prior to inclusion\n* Intravenous morphine treatment for more than 24 hours\n* Patient already included in the study within the previous 3 months\n* Patient receiving long-term opioid therapy\n* Not affiliated with a social security scheme, or patient under State Medical Aid (AME)\n* Patient under legal protection measures (guardianship \u002F family authorization with representation mandate \u002F future protection mandate) or under supervised guardianship (curatelle)\n* Patient deprived of liberty\n* Participation in another clinical trial involving a drug\n* Participation in the PAMAVOC trial within the previous 3 months\n* Contraindication to standard VOC treatment:\n* Hypersensitivity to opioids\n* Opioid-induced hyperalgesia, defined by increased pain on nociceptive testing, topographic extension, or the onset of allodynia with increasing opioid doses\n* Renal impairment, defined as creatinine clearance ≤30 mL\u002Fminute\n* Hepatocellular impairment, defined as prothrombin time \\\u003C40%\n* Impaired consciousness, defined as a Glasgow Coma Scale score ≤13\u002F15\n\nExclusion from a Specific Intervention (randomization possible to other study arms):\n\n* Hypersensitivity to the active substance or to any of the excipients\n* Respective contraindications to nefopam, tramadol, ketoprofen, and ketamine, as described in their respective Summaries of Product Characteristics (SmPC)","ALL","18 Years",{"count":152,"type":153},400,"ESTIMATED","INTERVENTIONAL",[156],"PHASE4","Sickle cell disease (SCD) is a severe hemoglobinopathy, characterized by recurrent vaso-occlusive crises (VOC) causing intense pain and frequent hospitalizations in adult patients. Current French and British guidelines recommend rapid administration of strong opioids, primarily through patient-controlled analgesia (PCA), as the reference treatment for hospitalized patients experiencing VOC. However, opioid use is associated with dose-dependent adverse effects, including nausea, constipation, pruritus, sedation, and hypoventilation, the latter representing a risk factor for acute chest syndrome.\n\nThe hypothesis underlying this study is that multimodal analgesia-combining morphine PCA with co-analgesics such as paracetamol-can significantly reduce morphine consumption during hospitalization compared to opioid-only analgesia, while maintaining effective pain control. Although several co-analgesic agents (paracetamol, NSAIDs, nefopam, tramadol, ketamine) are recommended by expert guidelines, including those from the American Society of Hematology (2020) and French recommendations (2025), the level of evidence supporting their use in adult sickle cell patients remains low or non-existent for most agents, with no randomized controlled trials available for nefopam, tramadol, or ketamine.\n\nUsing an adaptive platform design, this trial aims to compare multiple analgesic strategies against standard opioid-based care, generating higher-quality evidence to optimize pain management protocols for adult patients experiencing VOC",[159,160],"Sickle Cell Disease","Vaso-occlusive Crisis",[162,163,164,165,166],"Sickle cell disease","Multimodal Analgesia","Patient-Controlled Analgesia","Pain Management","Vaso-Occlusive Crisis","NOT_YET_RECRUITING","2026-09-11",{"date":170,"type":171},"2026-09-18","ACTUAL",{"date":173,"type":153},"2026-10-01",{"date":175,"type":153},"2030-01-01",{"name":5,"class":6}]