A Phase 4 interventional study of Group 02 Paracetamol + Morphine + Ketamine and Group 01 Control: Paracetamol + Morphine in Sickle Cell Disease and Vaso-occlusive Crisis, sponsored by Assistance Publique - Hôpitaux de Paris. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-18.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 4, Interventional, and Treatment
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
104 studies on the registry are indexed under Vaso-Occlusive Crises; 31 are open to participants now.
This study's planned enrollment of 400 is above the median of 81 across 86 interventional studies indexed under Vaso-Occlusive Crises.
Browse Vaso-Occlusive Crises studies →Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,592 studies on the registry; 1,033 are open to participants now.
Compared within Vaso-Occlusive Crises, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Anemia, Sickle Cell. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Exclusion from a Specific Intervention (randomization possible to other study arms):
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Group 01 Control: Paracetamol + Morphine
Drug: Group 02 Paracetamol + Morphine + Ketamine
Drug: Group 03 : Paracetamol + Morphine + Nefopam
Drug: Group 04 : Paracetamol + Morphine + Nefopam + Ketamine
Drug: Goup 05 : Paracetamol + Morphine + Tramadol
Drug: Group 6 : Paracetamol + Morphine + Tramadol + Ketamine
Drug: Group 7 : Paracetamol + Morphine + Ketoprofen
Drug: Group 08 : Paracetamol + Morphine + Ketoprofen + 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.
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
Drug pages: Acetaminophen · 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.
Drug pages: Acetaminophen · 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.
Drug pages: Acetaminophen · 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.
Drug pages: Acetaminophen · 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.
Drug pages: Acetaminophen · 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.
Drug pages: Acetaminophen · 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.
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.
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)
Transfusion Requirements
Number of red blood cell units transfused.
Time frame: From admission to discharge, assessed up to 14 days
Intensive Care Unit Admission
Admission to intensive care unit during hospitalization.
Time frame: From admission to discharge, assessed up to 14 days
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)
Length of Hospital Stay
Duration of hospitalization, measured in days
Time frame: From admission to discharge, assessed up to 14 days
Hyperalgic Vaso-Occlusive Crisis
Uncontrolled pain requiring morphine titration \>1 mg/kg or total intravenous morphine consumption \>2 mg/kg/24h.
Time frame: from randomization to discontinuation of intravenous opioid therapy Up to 14 days
Refractory Vaso-Occlusive Crisis
Visual analog scale (VAS) score \>7/10 after administration of study treatments and a new morphine titration (1 mg/kg).
Time frame: From randomization to discontinuation of intravenous opioid therapy Up to 14 days
Adverse Effects of Investigational Medicinal Products
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).
Time frame: Within 3 months (+/- 15 days)
In-Hospital Mortality
Death occurring during hospitalization.
Time frame: Duration of hospital stay, assessed up to 14 days
Unplanned Readmission
Unplanned hospital readmission within 3 months following the index hospitalization.
Time frame: Within 3 months (+/- 15 days) after discharge
No study locations are listed for this record.
Plan to share: No
No publications or documents are linked to this record.
Start is estimated for Oct 2026; primary completion for Oct 2029, 36 months later.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Acetaminophen · Morphine · Nefopam · Ketamine · Tramadol · Ketoprofen
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