Morphine Clearance and Glomerular Filtration in Sickle Cell Patients in Crisis in Intensive Care
PHEDREA
2 other identifiers
interventional
100
1 country
6
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Mar 2026
Typical duration for not_applicable
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 29, 2025
CompletedFirst Posted
Study publicly available on registry
November 24, 2025
CompletedStudy Start
First participant enrolled
March 5, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2028
March 10, 2026
March 1, 2026
2.5 years
August 29, 2025
March 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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
Secondary Outcomes (10)
Clearance of morphine and its metabolites M3G and M6G
24 hours
Morphine dose administered
24 hours
Morphine dose administred
Day 7
Pain progression using the Visual Analog Scale
Every 4 hours for the first 7 days
Pain progression using a Numeric Rating Scale
Every 4 hours for the first 7 days
- +5 more secondary outcomes
Other Outcomes (5)
Age of participant at inclusion
Inclusion
Socioeconomic Status According to EPICES (Evaluation de la précarité et des inégalités de santé dans les Centres d'examens de santé) Questionnaire
Inclusion
Presence of chronic medical conditions at inclusion
Inclusion
- +2 more other outcomes
Study Arms (1)
Determination of glomerular filtration rate by Iohexol
EXPERIMENTALFour 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Patient previously included in the study during a previous stay
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
CHRU de Tours
Tours, France, 37044, France
Henri-Mondor
Créteil, France
CH Le Mans
Le Mans, 72000, France
CHU de Nantes
Nantes, 44093, France
CHU d'Orléans
Orléans, 45067, France
CHU de Rennes
Rennes, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 29, 2025
First Posted
November 24, 2025
Study Start
March 5, 2026
Primary Completion (Estimated)
September 1, 2028
Study Completion (Estimated)
September 1, 2028
Last Updated
March 10, 2026
Record last verified: 2026-03