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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-511985-34-00 | EU Trial (CTIS) Number |
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Background: Sickle cell disease is a genetic disorder of haemoglobin (which carries oxygen in red blood cells). The shape of sickle cell-patients' red blood cells is abnormal. Thus, red blood cells can be blocked in small vessels, responsible for painful crises due to a lack of downstream circulation. These crisis (acute vaso-occlusive crisis) require strong treatment based on morphine, and often require intensive care.However, treatment is often insufficiently effective. Patient can also experiment acute chest syndrome, a complication of vaso-occlusive crisis, which can be responsible for respiratory failure. In addition, patients with sickle cell disease frequently have kidney damage called sickle cell nephropathy, which in the early stages of the disease is responsible for renal hyperfiltration, meaning that the kidneys filter the blood more than necessary, with faster elimination of drugs. For example, it is known that higher doses of antibiotics must be used in these patients than in the general population for the same effectiveness. The hypothesis of the study is that morphine, a drug eliminated by kidneys, is underdosed in patients with sickle cell disease, which is responsible for the difficulties in achieving sufficient analgesia.
Objective: To determine the glomerular filtration rate threshold for which it is necessary to prescribe higher doses of morphine in sickle cell patients with vaso-occlusive crisis.
Methods: inclusion of 100 patients admitted to intensive care for an acute vaso-occlusive crisis or acute chest syndrome and receiving morphine. Within 24 hours of study inclusion, four morphine dosages will be performed, in parallel with a precise determination of the glomerular filtration rate by measuring the elimination rate of a tracer, 100% eliminated by the kidneys and injected at the start of the study. This tracer is iohexol, a contrast agent commonly used in radiology. Morphine underdosage will be interpretated regarding glomerular filtration rate. The effectiveness of analgesia and the amount of analgesics required will be also be analyzed.
Outlook: At the end of this study, the investigators will be able to offer adapted doses of morphine for sickle cell patients in crisis, adapted to glomerular filtration rate, in the aim of personalizing analgesia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Determination of glomerular filtration rate by Iohexol | Experimental | Four morphine dosages, and a precise determination of the glomerular filtration rate by the measure of the elimination rate of iohexol will be carried out. The investigators will analyse in which patients and for which glomerular filtration rate there is morphine underdosage and simultaneously evaluate the effectiveness of analgesia and the amount of analgesics required. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Injection of iohexol for glomerular filtration rate (GFR) measurement | Drug | All patients will receive the same intervention. In included patients, 5 mL of iohexol will be injected, followed by blood sampling 5min, 1hr and 9hrs after iohexol injection for GFR measurement (as iohexol is known to be an exogenous maker for GFR measurement). Analgesia will be protocolized, based in particular on self-administered morphine (patient-controlled-analgesia). Morphine clearance will be measured thanks to 4 blood samples. Blood sampling for morphine and iohexol dosages will be synchronized in order to reduce the number of vascular punctures. Moreover, the first blood sample (5 minutes after iohexol injection) and the 4th blood sample for morphine dosage will be performed at the time of the daily biological analysis, still in order to reduce the number of vascular punctures. Thus, iohexol will be injected 5 minutes before the daily blood sampling for routine biological analysis. |
| Measure | Description | Time Frame |
|---|---|---|
| Therapeutic failure | Prediction of therapeutic failure based on glomerular filtration rate according to the CKD-EPI formula (area under roc curve). Therapeutic failure is defined as a percentage of relief assessed by the verbal numerical scale not reaching 30% within 24 hours. | 24 hours |
| Glomerular filtration rate according to the CKD-EPI formula | Glomerular filtration rate according to the CKD-EPI formula | 5 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Clearance of morphine and its metabolites M3G and M6G | Correlation between clearance of morphine (and its metabolites M3G and M6G) and glomerular filtration rate according to the CKD-EPI formula. | 24 hours |
| Morphine dose administered |
| Measure | Description | Time Frame |
|---|---|---|
| Age of participant at inclusion | Age of the participant in years at the time of study inclusion. This variable will be analyzed to assess its correlation with therapeutic failure at 24 hours. | Inclusion |
| Socioeconomic Status According to EPICES (Evaluation de la précarité et des inégalités de santé dans les Centres d'examens de santé) Questionnaire |
Inclusion Criteria:
Exclusion Criteria:
Exclusion criteria :
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Charlotte SALMON-GANDONNIERE, MD | Contact | +33 2 47 47 38 55 | poste 7 12 14 | charlotte.salmon.gandonniere@gmail.com |
| Coralie TAILLEBUIS | Contact | +332 47 47 39 09 | cpcq@chu-tours.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHRU de Tours | Recruiting | Tours | France | 37044 | France |
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Total dose of morphine administered during the day
| 24 hours |
| Morphine dose administred | Total dose of morphine administered each day | Day 7 |
| Pain progression using the Visual Analog Scale | Pain intensity will be assessed using the Visual Analog Scale (VAS), a 100-mm horizontal line ranging from 0 mm (no pain) to 100 mm (worst imaginable pain). Participants will indicate their pain level by marking a point on the line. Higher scores represent more severe pain. The change from baseline will be measured to assess pain progression. | Every 4 hours for the first 7 days |
| Pain progression using a Numeric Rating Scale | Pain intensity will be assessed using the Numeric Rating Scale (NRS), which ranges from 0 (no pain) to 10 (worst imaginable pain). Participants verbally rate their pain on this numeric scale. Higher scores indicate worse pain. | Every 4 hours for the first 7 days |
| Patient Global Impression of Change (PGIC) Over the First 7 Days | The Patient Global Impression of Change (PGIC) scale is a patient-reported outcome measure that assesses the patient's perception of change in their overall health status since the beginning of treatment. It is a 7-point Likert scale ranging from 1 (very much improved) to 7 (very much worse). Lower scores indicate a better outcome (improvement), while higher scores indicate worsening condition. PGIC will be assessed daily every 24 hours during the first 7 days of treatment. | Daily, every 24 hours, from Day 1 to Day 7 |
| Number of patients receiving paracetamol, nefopam, ketamine, NSAIDs, or nitrous oxide (MEOPA) within 24 hours | The therapeutic regimen will be recorded by counting the number of patients who receive each of the following analgesics within the first 24 hours: paracetamol, nefopam, ketamine, non-steroidal anti-inflammatory drugs (NSAIDs), and nitrous oxide (MEOPA). | 24 hours |
| Adverse effects of morphine | Adverse effects of morphine include impaired alertness, bradypnea, hypercapnia, pruritus, constipation, bloating, nausea, vomiting, and acute urinary retention. | Day 7 |
| Glomerular filtration rate according to the CKD-EPI formula | Basal glomerular filtration rate according to the CKD-EPI formula and crisis glomerular filtration rate according to the CKD-EPI formula (5 minutes) | 5 minutes |
| Plasma clearance of iohexol | Sample collection for iohexol dosage | 5 minutes, 1 hour et 9 hours |
Socioeconomic status will be assessed using the EPICES questionnaire, a validated tool to evaluate social deprivation. The score ranges from 0 (no deprivation) to 100 (maximum deprivation). This variable will be analyzed to assess its correlation with therapeutic failure at 24 hours. |
| Inclusion |
| Presence of chronic medical conditions at inclusion | Documentation of chronic pathologies or comorbidities present at the time of inclusion, based on medical history and patient records. This variable will be analyzed to assess its correlation with therapeutic failure at 24 hours. | Inclusion |
| Number of vaso-occlusive crises or acute chest syndrome episodes requiring hospitalization in the previous year | The number of hospitalizations due to vaso-occlusive crises or acute chest syndrome during the 12 months prior to inclusion. This variable will be analyzed to assess its correlation with therapeutic failure at 24 hours. | Inclusion |
| Number of unscheduled blood transfusions in the previous year | The number of non-programmed blood transfusions received by the participant during the 12 months prior to inclusion. This variable will be analyzed to assess its correlation with therapeutic failure at 24 hours. | Inclusion |
| Henri-Mondor | Not yet recruiting | Créteil | France |
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| CH Le Mans | Not yet recruiting | Le Mans | 72000 | France |
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| CHU de Nantes | Not yet recruiting | Nantes | 44093 | France |
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| CHU d'Orléans | Not yet recruiting | Orléans | 45067 | France |
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| CHU de Rennes | Not yet recruiting | Rennes | France |
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| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D000098644 | Vaso-Occlusive Crises |
| D056586 | Acute Chest Syndrome |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
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| ID | Term |
|---|---|
| D005919 | Glomerular Filtration Rate |
| D014894 | Weights and Measures |
| ID | Term |
|---|---|
| D007677 | Kidney Function Tests |
| D003950 | Diagnostic Techniques, Urological |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D014553 | Urinary Tract Physiological Phenomena |
| D012101 | Reproductive and Urinary Physiological Phenomena |
| D008919 | Investigative Techniques |
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