Adaptive Platform Trial for Pain Management During Vaso-Occlusive Crisis in Adult Patients With Sickle Cell Disease
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 400
- 主要终点
- Time to resolution of vaso-occlusive crisis (VOC)
研究概览
简要总结
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.
The 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.
Using 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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Group 01 Control : Paracetamol + Morphine
干预措施: Group 01 Control: Paracetamol + Morphine (Drug)
group 02 : Paracetamol + Morphine + Ketamine
干预措施: Group 02 Paracetamol + Morphine + Ketamine (Drug)
Group 03 : Paracetamol + Morphine + Nefopam
干预措施: Group 03 : Paracetamol + Morphine + Nefopam (Drug)
Group 04 : Paracetamol + Morphine + Nefopam + Ketamine
干预措施: Group 04 : Paracetamol + Morphine + Nefopam + Ketamine (Drug)
Group 05 : Paracetamol + Morphine + Tramadol
干预措施: Goup 05 : Paracetamol + Morphine + Tramadol (Drug)
Group 06 : Paracetamol + Morphine + Tramadol + Ketamine
干预措施: Group 6 : Paracetamol + Morphine + Tramadol + Ketamine (Drug)
Group 07 : Paracetamol + Morphine + Ketoprofen
干预措施: Group 7 : Paracetamol + Morphine + Ketoprofen (Drug)
Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine
干预措施: Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine (Drug)
结局指标
主要结局
Time to resolution of vaso-occlusive crisis (VOC)
时间窗: Up to 14 days after randomization.
Time to resolution of vaso-occlusive crisis is defined as the time from randomization to discontinuation of intravenous opioid therapy, measured in hours.
次要结局
- Intravenous Morphine Consumption(From admission to discharge, assessed up to 14 dayss))
- Transfusion Requirements(From admission to discharge, assessed up to 14 days)
- Intensive Care Unit Admission(From admission to discharge, assessed up to 14 days)
- Morphine-Related Adverse Effects(Within 3 months (+/- 15 days))
- Length of Hospital Stay(From admission to discharge, assessed up to 14 days)
- Hyperalgic Vaso-Occlusive Crisis(from randomization to discontinuation of intravenous opioid therapy Up to 14 days)
- Refractory Vaso-Occlusive Crisis(From randomization to discontinuation of intravenous opioid therapy Up to 14 days)
- Adverse Effects of Investigational Medicinal Products(Within 3 months (+/- 15 days))
- In-Hospital Mortality(Duration of hospital stay, assessed up to 14 days)
- Unplanned Readmission(Within 3 months (+/- 15 days) after discharge)