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

11 de septiembre de 2026 actualizado 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

Descripción general del estudio

Estado

Aún no reclutando

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Estimado)

400

Fase

  • Fase 4

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

  • Nombre: Samia BALOUL
  • Número de teléfono: 01 49 81 33 85
  • Correo electrónico: samia.baloul@aphp.fr

Copia de seguridad de contactos de estudio

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

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)

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Group 01 Control : Paracetamol + Morphine
Droga: 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
Droga: 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
Droga: 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
Droga: 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
Droga: 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
Droga: 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
Droga: 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
Droga: 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.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Time to resolution of vaso-occlusive crisis (VOC)
Periodo de tiempo: 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 resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Intravenous Morphine Consumption
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: Duration of hospital stay, assessed up to 14 days
Death occurring during hospitalization.
Duration of hospital stay, assessed up to 14 days
Unplanned Readmission
Periodo de tiempo: 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

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Assistance Publique - Hôpitaux de Paris

Investigadores

  • Silla de estudio: Ségolène GENDREAU, MD, PhD, Assistance public Hôpitaux de Paris

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Estimado)

1 de octubre de 2026

Finalización primaria (Estimado)

14 de octubre de 2029

Finalización del estudio (Estimado)

1 de enero de 2030

Fechas de registro del estudio

Enviado por primera vez

28 de julio de 2026

Primero enviado que cumplió con los criterios de control de calidad

11 de septiembre de 2026

Publicado por primera vez (Actual)

18 de septiembre de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

18 de septiembre de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

11 de septiembre de 2026

Última verificación

1 de julio de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

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

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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