Идёт набор NCT07246265

Morphine Clearance and Glomerular Filtration in Sickle Cell Patients in Crisis in Intensive Care

Без фазы С лечением Sickle Cell Disease Glomerular Hyperfiltration Sickle Cell Nephropathy Vaso-Occlusive Crises

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: Injection of iohexol for glomerular filtration rate (GFR) measurement.
Кому может быть актуально: Состояния в реестре: Sickle Cell Disease, Glomerular Hyperfiltration, Sickle Cell Nephropathy, Vaso-Occlusive Crises. Базовые параметры: от 18 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: Франция
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Обзор

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.

Вмешательства

Препарат Injection of iohexol for glomerular filtration rate (GFR) measurement
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 syn

Первичные конечные точки

Therapeutic failure [Срок оценки: 24 hours]
Glomerular filtration rate according to the CKD-EPI formula [Срок оценки: 5 minutes]

Вторичные конечные точки (10)

Clearance of morphine and its metabolites M3G and M6G [Срок оценки: 24 hours]
Morphine dose administered [Срок оценки: 24 hours]
Morphine dose administred [Срок оценки: Day 7]
Pain progression using the Visual Analog Scale [Срок оценки: Every 4 hours for the first 7 days]
Pain progression using a Numeric Rating Scale [Срок оценки: Every 4 hours for the first 7 days]
Patient Global Impression of Change (PGIC) Over the First 7 Days [Срок оценки: 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 [Срок оценки: 24 hours]
Adverse effects of morphine [Срок оценки: Day 7]
Glomerular filtration rate according to the CKD-EPI formula [Срок оценки: 5 minutes]
Plasma clearance of iohexol [Срок оценки: 5 minutes, 1 hour et 9 hours]

Критерии участия

Критерии включения

Patient ≥ 18 years old
Known homozygous sickle cell disease SS, SC, S-beta+, or S-beta0
Admitted in an intensive care unit
Clinical diagnosis of vaso-occlusive crisis and/or acute chest syndrome
Receiving PCA treatment with morphine
Patient's consent for study participation and/or from a relative if case of patient's incapacity
Affiliation to social protection

Критерии исключения

Patient previously included in the study during a previous stay
Injection of iodinated contrast medium outside the scope of the study within 24 hours prior to inclusion, or scheduled within 9 hours following the scheduled time of iohexol injection
Contraindication to iohexol: known or suspected immediate or delayed hypersensitivity, thyrotoxicosis.
Patient undergoing morphine treatment or substitution treatment such as methadone or buprenorphine prior to hospitalization (having received morphine or a derivative regardless of the route of administration in the week prior to hospitalization).
Chronic liver disease likely to interfere with morphine metabolism (cirrhosis )
Any condition that contraindicates the use of morphine according to the summary of product characteristics
Patients under legal protection
Pregnant or breastfeeding women