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

11 septembre 2026 mis à jour par: 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

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Estimé)

400

Phase

  • Phase 4

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

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 d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: Group 01 Control : Paracetamol + Morphine
Médicament: 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
Expérimental: group 02 : Paracetamol + Morphine + Ketamine
Médicament: 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.
Expérimental: Group 03 : Paracetamol + Morphine + Nefopam
Médicament: 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.
Expérimental: Group 04 : Paracetamol + Morphine + Nefopam + Ketamine
Médicament: 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.
Expérimental: Group 05 : Paracetamol + Morphine + Tramadol
Médicament: 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.
Expérimental: Group 06 : Paracetamol + Morphine + Tramadol + Ketamine
Médicament: 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.
Expérimental: Group 07 : Paracetamol + Morphine + Ketoprofen
Médicament: 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.
Expérimental: Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine
Médicament: 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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Time to resolution of vaso-occlusive crisis (VOC)
Délai: 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.

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Intravenous Morphine Consumption
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: Duration of hospital stay, assessed up to 14 days
Death occurring during hospitalization.
Duration of hospital stay, assessed up to 14 days
Unplanned Readmission
Délai: Within 3 months (+/- 15 days) after discharge
Unplanned hospital readmission within 3 months following the index hospitalization.
Within 3 months (+/- 15 days) after discharge

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Assistance Publique - Hôpitaux de Paris

Les enquêteurs

  • Chaise d'étude: Ségolène GENDREAU, MD, PhD, Assistance public Hôpitaux de Paris

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

1 octobre 2026

Achèvement primaire (Estimé)

14 octobre 2029

Achèvement de l'étude (Estimé)

1 janvier 2030

Dates d'inscription aux études

Première soumission

28 juillet 2026

Première soumission répondant aux critères de contrôle qualité

11 septembre 2026

Première publication (Réel)

18 septembre 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

18 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

11 septembre 2026

Dernière vérification

1 juillet 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

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

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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