Deze pagina is automatisch vertaald en de nauwkeurigheid van de vertaling kan niet worden gegarandeerd. Raadpleeg de Engelse versie voor een brontekst.

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

11 september 2026 bijgewerkt door: 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

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Geschat)

400

Fase

  • Fase 4

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

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)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: Group 01 Control : Paracetamol + Morphine
Geneesmiddel: 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
Experimenteel: group 02 : Paracetamol + Morphine + Ketamine
Geneesmiddel: 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.
Experimenteel: Group 03 : Paracetamol + Morphine + Nefopam
Geneesmiddel: 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.
Experimenteel: Group 04 : Paracetamol + Morphine + Nefopam + Ketamine
Geneesmiddel: 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.
Experimenteel: Group 05 : Paracetamol + Morphine + Tramadol
Geneesmiddel: 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.
Experimenteel: Group 06 : Paracetamol + Morphine + Tramadol + Ketamine
Geneesmiddel: 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.
Experimenteel: Group 07 : Paracetamol + Morphine + Ketoprofen
Geneesmiddel: 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.
Experimenteel: Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine
Geneesmiddel: 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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Time to resolution of vaso-occlusive crisis (VOC)
Tijdsspanne: 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.

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Intravenous Morphine Consumption
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: Duration of hospital stay, assessed up to 14 days
Death occurring during hospitalization.
Duration of hospital stay, assessed up to 14 days
Unplanned Readmission
Tijdsspanne: Within 3 months (+/- 15 days) after discharge
Unplanned hospital readmission within 3 months following the index hospitalization.
Within 3 months (+/- 15 days) after discharge

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Assistance Publique - Hôpitaux de Paris

Onderzoekers

  • Studie stoel: Ségolène GENDREAU, MD, PhD, Assistance public Hôpitaux de Paris

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 oktober 2026

Primaire voltooiing (Geschat)

14 oktober 2029

Studie voltooiing (Geschat)

1 januari 2030

Studieregistratiedata

Eerst ingediend

28 juli 2026

Eerst ingediend dat voldeed aan de QC-criteria

11 september 2026

Eerst geplaatst (Werkelijk)

18 september 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

18 september 2026

Laatste update ingediend die voldeed aan QC-criteria

11 september 2026

Laatst geverifieerd

1 juli 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

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

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Abonneren