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

NCT07826988 | Not Yet Recruiting Phase 4

• 2 other identifiers: APHP2512442026-527112-16-00
• Study Type: interventional
• Target: 400
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Vaso-occlusive Crisis; Sickle Cell Disease

Keywords

Sickle cell disease; Multimodal Analgesia; Patient-Controlled Analgesia; Pain Management; Vaso-Occlusive Crisis

Outcome Measures

Primary Outcomes (1)

• Time to resolution of vaso-occlusive crisis (VOC)

  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.

Secondary Outcomes (10)

• 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

Study Arms (8)

Group 01 Control : Paracetamol + Morphine

ACTIVE COMPARATOR

Drug: Group 01 Control: Paracetamol + Morphine

group 02 : Paracetamol + Morphine + Ketamine

EXPERIMENTAL

Drug: Group 02 Paracetamol + Morphine + Ketamine

Group 03 : Paracetamol + Morphine + Nefopam

EXPERIMENTAL

Drug: Group 03 : Paracetamol + Morphine + Nefopam

Group 04 : Paracetamol + Morphine + Nefopam + Ketamine

EXPERIMENTAL

Drug: Group 04 : Paracetamol + Morphine + Nefopam + Ketamine

Group 05 : Paracetamol + Morphine + Tramadol

EXPERIMENTAL

Drug: Goup 05 : Paracetamol + Morphine + Tramadol

Group 06 : Paracetamol + Morphine + Tramadol + Ketamine

EXPERIMENTAL

Drug: Group 6 : Paracetamol + Morphine + Tramadol + Ketamine

Group 07 : Paracetamol + Morphine + Ketoprofen

EXPERIMENTAL

Drug: Group 7 : Paracetamol + Morphine + Ketoprofen

Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine

EXPERIMENTAL

Drug: Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine

Interventions

Group 02 Paracetamol + Morphine + Ketamine DRUG

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.

group 02 : Paracetamol + Morphine + Ketamine

Group 01 Control: Paracetamol + Morphine DRUG

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

Group 01 Control : Paracetamol + Morphine

Group 03 : Paracetamol + Morphine + Nefopam DRUG

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.

Group 03 : Paracetamol + Morphine + Nefopam

Group 04 : Paracetamol + Morphine + Nefopam + Ketamine DRUG

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.

Group 04 : Paracetamol + Morphine + Nefopam + Ketamine

Goup 05 : Paracetamol + Morphine + Tramadol DRUG

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.

Group 05 : Paracetamol + Morphine + Tramadol

Group 6 : Paracetamol + Morphine + Tramadol + Ketamine DRUG

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.

Group 06 : Paracetamol + Morphine + Tramadol + Ketamine

Group 7 : Paracetamol + Morphine + Ketoprofen DRUG

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.

Group 07 : Paracetamol + Morphine + Ketoprofen

Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine DRUG

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.

Group 08 : Paracetamol + Morphine + Ketoprofen + Ketamine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Refusal to participate
• Pregnant or breastfeeding patient
• 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%

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Anemia, Sickle Cell; Vaso-Occlusive Crises; Agnosia

Interventions

Morphine; Ketamine; Nefopam; Tramadol; Ketoprofen

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Oxazocines; Azocines; Heterocyclic Compounds, 1-Ring; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Dimethylamines; Methylamines; Amines; Lipids; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Ségolène GENDREAU, MD, PhD

  Assistance public Hôpitaux de Paris

  STUDY CHAIR

Central Study Contacts

Samia BALOUL

CONTACT

01 49 81 33 85; samia.baloul@aphp.fr

Ségolène GENDREAU

CONTACT

01.45.17.85.06; segolene.gendreau@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2026
• First Posted: September 18, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 14, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: September 18, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share