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

ConditionsSickle Cell DiseaseVaso-occlusive Crisis
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorAssistance Publique - Hôpitaux de Paris

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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 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 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 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.

  • 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 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 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 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.

Treatment groups

400 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: Group 01 Control : Paracetamol + MorphineActive comparator 1 intervention
Group B: group 02 : Paracetamol + Morphine + KetamineExperimental treatment 1 intervention
Group C: Group 03 : Paracetamol + Morphine + NefopamExperimental treatment 1 intervention
Group D: Group 04 : Paracetamol + Morphine + Nefopam + KetamineExperimental treatment 1 intervention
Group E: Group 05 : Paracetamol + Morphine + TramadolExperimental treatment 1 intervention
Group F: Group 06 : Paracetamol + Morphine + Tramadol + KetamineExperimental treatment 1 intervention
Group G: Group 07 : Paracetamol + Morphine + KetoprofenExperimental treatment 1 intervention
Group H: Group 08 : Paracetamol + Morphine + Ketoprofen + KetamineExperimental treatment 1 intervention

Trial outcomes

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.

Time frame
Up to 14 days after randomization.

Secondary outcomes

1

Intravenous Morphine Consumption

Cumulative dose (mg) and mean daily dose (mg/day) of intravenous morphine.

Time frame
From admission to discharge, assessed up to 14 dayss)
2

Transfusion Requirements

Number of red blood cell units transfused.

Time frame
From admission to discharge, assessed up to 14 days
3

Intensive Care Unit Admission

Admission to intensive care unit during hospitalization.

Time frame
From admission to discharge, assessed up to 14 days
4

Morphine-Related Adverse Effects

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).

Time frame
Within 3 months (+/- 15 days)

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Assistance Publique - Hôpitaux de Paris

Lead sponsor

Source ClinicalTrials.gov

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