Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

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

11 de setembro de 2026 atualizado por: Assistance Publique - Hôpitaux de Paris

Adaptive Platform Trial for Pain Management During Vaso-Occlusive Crisis in Adult Patients With Sickle Cell Disease

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

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Estimado)

400

Estágio

  • Fase 4

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

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)

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Comparador Ativo: Group 01 Control : Paracetamol + Morphine
Medicamento: 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
Experimental: group 02 : Paracetamol + Morphine + Ketamine
Medicamento: 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.
Experimental: Group 03 : Paracetamol + Morphine + Nefopam
Medicamento: Group 03 : Paracetamol + Morphine + Nefopam
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.
Experimental: Group 04 : Paracetamol + Morphine + Nefopam + Ketamine
Medicamento: Group 04 : Paracetamol + Morphine + Nefopam + Ketamine
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.
Experimental: Group 05 : Paracetamol + Morphine + Tramadol
Medicamento: 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.
Experimental: Group 06 : Paracetamol + Morphine + Tramadol + Ketamine
Medicamento: 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.
Experimental: Group 07 : Paracetamol + Morphine + Ketoprofen
Medicamento: 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.
Experimental: Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine
Medicamento: Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine
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.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Time to resolution of vaso-occlusive crisis (VOC)
Prazo: 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.
Up to 14 days after randomization.

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Intravenous Morphine Consumption
Prazo: From admission to discharge, assessed up to 14 dayss)
Cumulative dose (mg) and mean daily dose (mg/day) of intravenous morphine.
From admission to discharge, assessed up to 14 dayss)
Transfusion Requirements
Prazo: From admission to discharge, assessed up to 14 days
Number of red blood cell units transfused.
From admission to discharge, assessed up to 14 days
Intensive Care Unit Admission
Prazo: From admission to discharge, assessed up to 14 days
Admission to intensive care unit during hospitalization.
From admission to discharge, assessed up to 14 days
Morphine-Related Adverse Effects
Prazo: Within 3 months (+/- 15 days)
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 (+/- 15 days)
Length of Hospital Stay
Prazo: From admission to discharge, assessed up to 14 days
Duration of hospitalization, measured in days
From admission to discharge, assessed up to 14 days
Hyperalgic Vaso-Occlusive Crisis
Prazo: from randomization to discontinuation of intravenous opioid therapy Up to 14 days
Uncontrolled pain requiring morphine titration >1 mg/kg or total intravenous morphine consumption >2 mg/kg/24h.
from randomization to discontinuation of intravenous opioid therapy Up to 14 days
Refractory Vaso-Occlusive Crisis
Prazo: From randomization to discontinuation of intravenous opioid therapy Up to 14 days
Visual analog scale (VAS) score >7/10 after administration of study treatments and a new morphine titration (1 mg/kg).
From randomization to discontinuation of intravenous opioid therapy Up to 14 days
Adverse Effects of Investigational Medicinal Products
Prazo: Within 3 months (+/- 15 days)
Including nefopam (seizure); NSAIDs (acute kidney injury, KDIGO stage >0; gastrointestinal or other bleeding); tramadol (seizure, liver function abnormalities, impaired consciousness with GCS <14/15); ketamine (liver function abnormalities, hallucinations, impaired consciousness with GCS <14/15, venous access complications).
Within 3 months (+/- 15 days)
In-Hospital Mortality
Prazo: Duration of hospital stay, assessed up to 14 days
Death occurring during hospitalization.
Duration of hospital stay, assessed up to 14 days
Unplanned Readmission
Prazo: Within 3 months (+/- 15 days) after discharge
Unplanned hospital readmission within 3 months following the index hospitalization.
Within 3 months (+/- 15 days) after discharge

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Assistance Publique - Hôpitaux de Paris

Investigadores

  • Cadeira de estudo: Ségolène GENDREAU, MD, PhD, Assistance public Hôpitaux de Paris

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

1 de outubro de 2026

Conclusão Primária (Estimado)

14 de outubro de 2029

Conclusão do estudo (Estimado)

1 de janeiro de 2030

Datas de inscrição no estudo

Enviado pela primeira vez

28 de julho de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

11 de setembro de 2026

Primeira postagem (Real)

18 de setembro de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

18 de setembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

11 de setembro de 2026

Última verificação

1 de julho de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • APHP251244
  • 2026-527112-16-00 (Ctis)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Se inscrever